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by: Mrs. Willis Mante


Mrs. Willis Mante

GPA 3.6

Kevin Jones

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Kevin Jones
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This 136 page Class Notes was uploaded by Mrs. Willis Mante on Thursday October 29, 2015. The Class Notes belongs to MCDB 4777 at University of Colorado at Boulder taught by Kevin Jones in Fall. Since its upload, it has received 19 views. For similar materials see /class/231837/mcdb-4777-university-of-colorado-at-boulder in Molecular, Cellular And Developmental Biology at University of Colorado at Boulder.

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Date Created: 10/29/15
MCDB 47775777 LTD turning synapse strength down Molecular Neurobiology I39I the hippocarnpus L ecmre 36 in the cerebellum Regeneration and Repair Spike timing andthe importance orternporal context Types of regenerationlrepair Peripheral nerve regeneration Responses to injury in the brain Adult neurogenesis g 20 0 20 40 60 so t we mi 1 Time min mammals leulh mm Figu Mle n h hmusclmm mm Editw hemYr Iaru Figure 816 Longterm synaptic depression in the cerebellum Part 3 C quotsumsciavcs Fnurlh Edition Figure ms pm a 247 Pairing presynaptic and postsynaptic activity causes LTP Part 2 EPSP amplitude mv c M N rImidl Figure 816 Longterm synaptic depression in the cerebellum Part 4 D Climbing fiber Purkinje cell dendritic spine alumna K usunoscmvce Fourth Edition Figure 316 For 4 uranium w Figure 817 Spike timingdependent synaptic plasticity in cultured hippocampal neurons Part 1 Strong depolarizing pulses paired with I SPs Test 2 Presynaptic before puslsynaptic on o 1 o mo baaro L I m post Postsynapti membrane patenrial mV EPSC amplitude Vn of contml gt10 0 10 Time min 50 70 70 Time ms 20 30 40 U Time min 535m m LTP is statedependent pairing of a weak stimulus that wouldn t cause LTP w depolarization win 100ms leads to LTP swamr mumm usunosclavcs Fourth Edition Fiaun 517 mm 1 Figure 817 Spike timingdependent synaptic plasticity in cultured hippocampal neurons Part 3 Figure 817 Spike timingdependent synaptic plasticity in cultured hippocampal neurons Part 2 E Postsynaptic before c m 53 mo 5 40 5 l 5 9 g l g E g 140 m E 7 0 j a V a a 39U g 100 Fred3945 E a g g 40 a I D L E 60 l O 20 40 60 L 20 Time ms Time min quotmommaquot Foam EdMon Flguru 311 Part2 quot3 Figure 252 Three types ofnervous system repair or regeneration t Mm 4quot 7 it t t NEUROSCIENCE Fourth Edmon Flgurc 252 mm K E EPSC amplitude quoto of control Interval between presynaptic and postsynaptic activity ms usunoscIENcE Fourth sumquot gur 311 Pm a quotW a Figure 252 Three types ofnervous system repair or regeneration Part 1 A Preinjury Injury Post recovery l Neuron in CNS or PNS Peripheral target NEUROSCIENCE Fourth Edition Figun 252 Part 1 mu 2 Figure 252 Three types ofnervous system repair or regeneration Part 2 Postrecovery B Pre injury CNS source Central or peripheral target NEUROSCIENCE Fourth Edmon Flynn 252 Pan 2 Figure 2 3 Henry Head39s peripheral nerve regener n experime A Site of cut xtemal n 5 0 rs E E a Site 97 cut Super cial radial nerve u NEUROSCIENCE Fourth Edition Figure 255 Figure 252 Three types ofnervous system repair or regeneration Part 3 CNS source Central or peripheral target NEUROSCIENCE Fourth Edition Figure 252 Part a Figure 25 Regenera n peripheral nerves A 3 Poxineurium Nerve Nerve ma mquot Growth Macmpha 25 C and axonal cbris NEUROSCIENCE Fourth Edition name 254 Figure 255 Molecular and cellular responses that promote peripheral nerve regeneration Figure 257 Reinnveration ofmuscles following peripheral motor nerve damage Part 1 I vnphi ml n r mh mm l nmnui m miuri mm m mmrx nun m 4 I 39 V I pt39ril liiml mm mwmn w J A Iurnm l m n on d R mm n and Myelin n n mutur nun u lm39mphm mpulh nn Nerve ml thbL hJ fibers ii at a MPH nun l gmhllmrlukul 9 mm 45 xnn zmml39r ramming signals NEUROSCIENCE Enunh Edllion Figure 255 C NEUROSCIENCE Faunh Edition Figure 257 Pan 1 Figure 257 Reinnveration ofmuscles following peripheral motor nerve damage Part 2 Figure 258 Consequences ofhypoxia schemia in the mammalian brain Part 1 Bl Schwaan culls Axum Acctylchulinc rucuplur I minjury 25 day later NEUROSCIENCE Fnurlh Edition Figure 257 Part 2 t NEUROSCIENCE Fourth Edition Figure 258 Part I r t w Figure 258 Consequences ofhypoxia schemia in the mammalian brain Part 2 Figure 259 The reaction of the three major classes of CNS glia to local tissue damage B 7 39 39 i V i VT Unin39ured ln39ured Stimuli for apoptosis ym he l o Uniniured Injured Glutamate E E Q m B 5 g lt Oligudendmglia NGZ K g NEUROSCIENCE Fourth Edllion Figure 258 Pan 2 Figure 2510 Cellular response to injury in the central nervous system Figure 256 Peripheral nerve sheaths and Schwann cells facilitate growth of damaged axons anmnl m muln39 mm In Injury 39hmu NEUROSCIENCE Fourth Edllion Figure 2510 NEUROSCIENCE Fourth Edmon Figure 256 Figure 2511 Adult neurogenesis in nonmammalian vertebrates Part 1 Figure 2511 Adult neurogenesis in nonmammalian vertebrates Part 2 B A Ventricle Retinal quot x V gmwlh Neuronal precursor radial gm cell Migmtin nuumblad Old ncumn Tu A rm X r 3 Outer nut lcm39 hr 1 39 layer rodsonus r 39 Inncr nuclear layer 39 bipolar cells Retinal gtgangliun culls v Retinal precursor elk Brmnslem mnmr ncumns l NEUROSCIENCE Fourth EdIIian Figure 2511 Park 1 NEUROSCIENCE Fourth Edition Figure 25quot Par 2 Figure 2512 Neurogenesis in the adult mammalian brain Part 1 A Figure 2514 New neurons in the adult brain migrate via a speci c pathway A Rnatml migratory m mm RMS Corpus callosum Olfactory bulb CuminHum Lateral wall of lateral ventricle Proliferatng precursors in the anterior subventricular zone NEUROSCIENCE Faunh Edition Figure 2512 Part 1 v w AW NEUROSCIENCE Fourth Edih39on Figure 2514 Figure 2512 Neurogenesis in the adult mammalian brain Part 2 Figure 2513 The forebrain anterior subventricular zone constitutes a stem cell niche Molecular Hippocampal A layer formation n Bventricular zone Lateral ventricles Anterior gt1 sulwenlricular hl K 1 dmel Trans amplifying Zl lnc cells With cilia cell 3 NEUROSCIENCE Fourth Edition Figum 2513 E a M NEUROSCIENCE Fourth Edition Figure 2512 Part 2 z u Box 2531 NuclearWeapons and Neurogenesis Part 2 Box 2531 NuclearWeapons and Neurogenesis Part 1 renmtm curb I 1950 B Individual burn in 1952 Tempmal Occipual 1960 a 1953 800 m a 7m 1970 g 0 7 6L Atmospheric 1quotC in 500 concentration 1980 quot Neurons Numneumns r A 1990 I l rcf runtal I Parietal I I 2005 umpuml I I Premmnr HCamm 14C cunccntmtk NEUROSCIENCE Faun2h Edition Box 253 1 Pan 2 NEUROSCIENCE Fourth Edl on Box 253 1 Part 1 HC concentration change tram baseline 0 J 8 NEUROSCIENCE Fourth Edition Box 255 1 van a I Prefrnntal I Parietal I Temporal I Premntor hung 5 a E N mumlnmm v39v flung 1mm tavth a E I NEUROSCIENCE Fourth Edition Box 255 1 Indlvldul hum h m magma MCDB 47775777 Molecular Neurobiology Lecture 12 Synapse mechanisms the rich diversity of neurotransmitters and their receptors Goals for today Synthesis and removal of the major small molecule neurotransmitters Acetylcholine Glutamate Gaba Glycine For each how are they synthesized Removed Where do they act Related drugs and diseases 520 Summation of postsynaptic potentials Part 1 A 31 2 r Excitatory E1 A Record Postsynaptic membrane potential Inhibitory I W 1 Excitatory E2 520 Summation of postsynaptic potentials Part 2 B Postsynap c membrane poten al mV Time ms gt 521 Events from neurotransmitter release to postsynaptic excitation or inhibition Postsynaptic cells excited or inhibited NEUHDSGIENGE Third Ediliorl gure 521 e 2004 Simmer Assadmes m Box A Criteria That De ne a Neurotransmitter a ternunal Present in presynaptic terminal detection Biosynthetic enzymes other fxns Presynaptic Released in response to depolarization Ca dependent synapses often smallinaccessible transmitters rapidly removed Specific receptors present on postsynaptic cell often easier but limited by specific reagents 61 Examples of smallmolecule and peptide neurotransmitters Part 1 SMALLMOLECULE NEUROTRANSMITTERS r H Acetylchollne CI133N CHZ CHZ O C CHJ AMINO ACIDS Glutamate 31539 El COO39 le 2H2 OOH Aspartate H3141 I3 COO cle OOH GABA H3N CH3 CH2 CHZ COO Glycine H3N lg COO 1L 1 swan 62 Acetylcholine metabolism in cholinergic nerve terminals Na Choline Presynaptic transporter terminal Choline Vesicular ACh transporter Postsynaptic cell NEUROSCIENCE Third Edition gure 62 ta 2004 smauev Assodal mu 63 The structure ofthe nACh receptorchannel Part 1 63 The structure ofthe nACh receptorchannel Part 2 D ptor Membranel Rece mm n9 B Maryl g 35356 M m hie Wm Banded krait bungarotoxin Liz 739 L Cone snall Betel nuts conotoxms arecoline f h anun Box 0 Myasthenia Gravis An Autoimmune Disease of Neuromuscular Synapses B EMG recording of muscle Number of MEPPs action potentials mV Normal D 4 0 4 020406080 020 40 60 80 Time ms 15 Myasthenia Norma avis 10 gr r 39 5 1 5 005 010 020 050 1 20 3 MEPP amplitude mV Myasthenja gravis Myasthenia gravis after neostigmine treatment 0 20 40 60 m 80 61 Examples of smallmolecule and peptide neurotransmitters Part 1 SMALLMOLECULE NEUROTRANSMITTERS r H Acetylchollne CI133N CHZ CHZ O C CHJ AMINO ACIDS Glutamate 31539 El COO39 le 2H2 OOH Aspartate H3141 I3 COO cle OOH GABA H3N CH3 CH2 CHZ COO Glycine H3N lg COO 1L 1 swan 66 Glutamate synthesis and cycling between neurons and glia Presynaptic terminal I ll HaN CH CHZ CHZ C NHZ NHJ CH CHZ CHZ COO VGLUT Postsynaptic cell Glutamate receptors NEUROSCIENCE Third Edition gure 66 tn 2004 Smauev Associates mu 64 The general architecture of ligandgated receptors Part 1 64 The general architecture of ligandgated receptors Part 2 n um um I 67 NMDA receptors A Glutamate Glycine Mg2 A Mg2 binding F nnmn l Pan 1 67 NMDA and AMPAkainate receptors Part 2 EPSC pA No glycine 50 no Mg2 100 150 100 50 0 50 100 Membrane potential mV r I a Panz 67 NMDA and AMPAkainate receptors Part3 C EPSC pA EPSC pA EPSC pA O 25 50 75 100 Time ms Flnnm a 1 pm a Exam 1 zany Grads mums 334 15 23 25 an 35 an 45 su 55 an 55 7a 75 Eu as 93 9s 19242934394 4954595 59747 3459913 score MCDB 47775777 Molecular Neuroblology Lecture 39 Alzhelrner39s Dlsease Alzheimer s Disease The Scope ofthe Problem How many ofyou know someone Wth Alznelrner39s dlsease7 5 rnllllon Amencans amlcted today only cancer and heart dlsease affectrnore Amencans 12 million wlll have AD ln 2050 8 yrs average from dragnosls to death some llye 20 yrs lt5 between 65 and74 lncldence doubles every 5 yrs alter 657 Age lsm nskfactor gt50 over age 85 Outline of Today s Lecture eryls Alznelrner39s drsease aproblem7 Whatls Alznelrner39s Dlsease7 What causesAlznelrner39s drsease7 How can we test whether somethlng causes the dlsease7 How can we trytornterfere wth the cause7 l e develop adrug to treat the dlsease How can we qulckly andsafelytestwhetherthe drug may Work7 US Pnpulau39un 65 and Olda 19901050 Census Data and Middle Series Pruiecu39uns HEEEEEEEBE E E E E US Population 85 and Older 19902050 Census Data and Middle Series Projections Em IE m w m 1 m I m III m M EEC I I I m m amBEBE I f I What is Alzheimer s Disease Progressive Symptoms increasing memory loss and confusion poor judgment mood changesanxietyaggression inability to recognize people language and cognitive difficulty agitation restlessness and wandering seizures infections sometimes severe loss of bladder and bowel control hallucinations and delusions What is Alzheimer s Disease The most common of the dementias about 50 70 of all cases Dementia loss of memory intellect rationality social skills and normal emotional reactions Early phase symptoms memory loss vagueness taking longer to do routine tasks losing conversations or repeating oneself quotWith Alzheimer s people there s no such thing as having a day which is like another day Every day is separateit s as if every day you have never seen anything before like what you re seeing right nowquot Cary Henderson a History Professor in Virginia speaking about his experience with having the disease In the late phase of the disease patients can no longer care for themselves httpWWW alsz asn auflibrarydementia htm httpWWW alzheimers orgunmvel htmltop Table L Criteria for clinical diagram of Alzheimer s disease my neurnlwlv innumiznn m um gumnu mun mu mun advmrId mum ml intnunquot mmo um m a 4 7 I mi 1 I 1 1 le r mm I39ur w rlmtrnl migwniia nr PHOBA Ru Aldluunu r mum mrludv In on MmNaIIuI Tau Blnwd Dcmsmm scnh nr sum un39nhu mun1mm and mnIumd m IIrIIvIII vhIIIgpIII eels mum m Jdvnncrd mime and CT nuIrrml m w Iluinr m vnmrmrlrz mullingmm l rumw um mm m mamas ur PROBABLE Alxhilmu i n yNumamv mm ul mm mm mm wmlm mm quotMN MW quotquotml39kd39v 1 6 Hum mud uwpIIruc um mdmwtmmunmnmnusa qu nusmlnglr Imam lturlI n hymn unis uniuvy 1er u r I m r umbzcunvauumnmd Ur manorn Mm m m ml 3 quotd39mwmmm Rm39 m mquot quotr i Mbwncc M iyltemic dmni u urullm hmn dusam mm m and m Ihrmneh as wIIld Itcnnnl Im me nmgmmvk dvflml m mvlnun nnd rnllnmm mum m dwlmhamsu av mz muaI m wn ulrlv m m mum r use Luna IL39l39h Iimumnnl 39quot 39l 39 39 r e ll L 4 u may he quotmay nu un mm m hemmenus syndmmu m m lsnmnm I m nntxmn mm A l huva 1mm mum of mu leden puLIuIZally I mama mun ulv lmllymld 1mm rpmi Ur mnmml 1mm yummy u mmer In mndm Ink anbes mum palm or mnwpu lu ihlngrs in am mm m Increased alvawm39e mu m and manna un bml Mmpny vm I39T mm p lmssmn mm mummy mm uhsrrvmliun in Lima mum tumr6 muan mm Ih dusgmms nl PHI BA cl BLE Alll ullllzr a dmum anquot n um a mum ul dementia umrr hm AlIhaIrIIrI39s dump in plateaus m Um nun m mum VI in mum mocme ympmml I deynnum Inwmma mmmmm I Hummus illnsmni lml lucuuuuns muulmihii 21lm umu mud or plwnrnl Ilulhunl mum damquot and mm was m m nnstl m lha pwwnlalhm m In ow Ilium mm IJNIHJN Minim mmqu drmmrix whu39h is H mm m vI be m mm I m damnmm mm quth be usequot m march 4391le when I shale wallml pmwaumumgmmmmu u Lennmum lhcnl rnu m Mth ulcnhhnhlr unm 39l nmu Hr anng nmNITI r l lk llm39l39 mm m quotIII 39lmk ul quotlen lur Mohamm Alinelm r j dun u IIrIIl mumwrnw mum ummwi I 3 mm 4quot Vll flaasilimlinn ul magnum Mm I mm39n purplish nhvmld and mum um um dulmmuu mam m Inn qu lk h as 39mlIlIll umIrnnnv mm below In men prvsenc I mom 2 Mn mummies rd mm velrvlml mumm my u l nrkIIllnn39lt 39 Ft r r i n healthy advanced p O alzheimer39s Plaques and tangles shovm in the blueshaded areas tend to spread through the cortex in a predictable pattern as Alzheimer s disease progresses The rate ofprogression varies greatly People with Alzheimer s live an average of eight years but some people may survive up to 20 years The course ofthe disease depends in part on age at diagnosis and whether a person has other health conditions Earliest Alzheimer39s changes may begin 20 years or more before diagnosis Mild to moderate Alzheimer stages generally last from 2 10 years Severe Alzheimer s may last rom 1 5 years rom AMANalzorg From vwmalzorg What Causes Alzheimer s Disease Alois Alzheimer a German doctor published a paper in 1907 describing the case of a woman having dementia After she died he had autopsied her and found deposits in her brain What is in the plaques and tangles Amyloid plaques were found to be composed mostly of extracellular deposits of 5 amyloid also called A 5 a small 40 The deposits are called Amyloid 42 amino acid Pemida Plaques and Neuro brillary Tangles V Neuro brillary tangles were found to contain highly phosphorylated tau a microtubule associated protein Amy101d Plaque For reasons that will soon become apparent we ll concentrate Neme bnllary Tangles primanly on the S amyloid side of the story mp www alznsw asn aultbrarydemenha him mp www mam cumZUEIEIl znmssuei ZUUStgeurge html What are the genetics of Alzheimer s disease As geneticists studied AD two general patterns emerged Early Onset Familial Alzheimer s Disease FAD Age 30 60 onset apparent inheritance of a dominant trait through generations perhaps 5 10 of total cases mutations known in 10 of these cases thus less than 1 of total Sporadic Alzheimer s Disease Later onset inheritance of a trait not apparent accounts for majority of cases Proteolytic Processing of the Amyloid Precursor Protein Generates amyloid peptide Processing Pathways 1 01 y secretases gives p3 peptide 2 5 y secretases gives 540 peptide 3 5 y secretases gives 542 peptide insoluble Preseriilinil is necessary for y secretase activity The genetics of EarlyOnset Familial Alzheimer s Disease Mutations were found in the following genes The Presenilins are membrane proteins involved in proteolytic processing thought to be y secretase components Presenilin 1 Presenilin 2 This is the protein that Amyloid Precursor Protein BAPP is processed to give the B amyloid peptide SAPP mutations account for less than 01 of total AD cases but have virtually complete penetrance Mutations in the amyloid Precursor Gene Cm 39 AQ Cytoplasm 595 1 4 quot 3 quot 3 quot a 40 5 or O 42 va MSGYWQKLVFYWSSNKGAIIGLHVGGWIA T V IVITLWLKKKQ I I NL G 0 0 Fe o f 0 0 Swedish Hemrncs Duld l 717 double quotMalian mutation mutation mmanons Dmmm n m sum l N h H M N v m m The Amyloid Hypothesis Production of AB especially the relatively insoluble A642 Formation of extracellular deposits Neuron atrophy and death Alzheimer s disease According to this hypothesis FAD mutations enhance the production of A 42 EC t mj W Synthesized K APP i39 Recytling endusome l The SORLl protein directs APP into recvding endosornes which shuttle it to the ceii membrane But when SORLl is absent APP goes instead to the iate endosorneswhere the enzymes RACE and P51 snip out neurotoxic amvlo d 5c ence 19lan 2007 p 314 The genetics of Alzheimer s Disease Susceptibility genes Having one ApoEA allele 5X increase in risk Having 2 ApoE4 alleles 15X increase in risk 3 alleles at this locus ApoE2 ApoE3 ApoE4 ApoE protein important in lipid transport somehow relevant to amyloid deposition SORLl amyloid processing association study published 107 con rmation DOMIMN ILV INNEHlTED NONDOIMNANT FORMS OF AD rams OF AD Iridium Wicum Plssanllln 1 or 2 guns 34 lnhevimnce of ApoEd hurry AD riagra l V ll creased A342 produmlnn Ihvwnhw quot10 annually rising An larval mm 9 Suhlla nurses at 5342 ollgomers on synaptic ammy I a an Grimm deposition 01A mum is dl uu plaques 4 Mimgual and aslmcyu c activation Ind attendanl in ammatory raw Mama murmur ionic homeoslasis oxmalwo inury Selkoe 2002 Science Mom klnusalpnospham mums load In mnqios wmsapmarr neuronalsynaptic murmur and selective naumnal loss with anandull naurorruisrrimi notions DEMENTM Cholinesterase Inhibitors The US Food and Drug Administration FDA has approved two classes of reat cognitive symptoms of Alzheimer39s disease The irst drugs to t f Alzheimer med iCath Teme ii ia TnhgitDrSI Three of these dru s are commonl rescribed donepezil Aricept appro39FiT rivastigmine Exelon approved in 2000 galantamine approved in 2001 under the trade name Reminy and 05 renamed Razadyne in 20 Memantine Mernantine Namenda is a drug approved in October 2003 bv tne FDA tor treatment orrnoderate to severe Alzheimer39s disease Memantine i5 ciassined as an uncompet tive ioWatoamoderate attinitv NamethviaDaaspartate NMDA receptor antagonist tne first Alzheimer drug of tnis tvpe approved in tne United states Sourcei WWW aiz org How might we interfere with accumulation 1 Inhibit B or y secretases Z Enhance clearance of B42 peptide How can we test Whether these mutations cause the disease Introduce FAD mutations into mice Transgene DNA construct FAD mutantgene Mouse chromosome FAD mutant gene mutant version of amyloid precursor gene or presenelin gene Does the mouse have symptoms of AD Some Promising Results in Mice 1 Administration of B secretase inhibitor in transgenic mice can reduce AB accumulation 2 Administration of antibodies that react with AB reduces AB accumulation and improves behavioral performance 3 Immunization with AB reduces AB accumulation and improves behavioral performance a M a T 39pm t r T mm mrre 39 39 L 439 39L 39 I A plaques labeled by Dako 6F3D andrA antibody in the hippocampus A and B and comx c and D of control pepu39 er immunized A and C and A42rimmunized TgCRNDS mice B and D Scale bars 100 ym PNAS October 5 2004 vol 101 Suppl 2 1465114662 A paradigm for developing treatments for human genetic diseases Human genetics Discovery of disease genes and their mutations Transgenic mice carrying disease mutations Testing of therapeutic strategies in mice transgenic mice Testing of therapeutic strategies in humans Effective treatment of disease Neurology 2003 614654 03 Ameneau Academy of Neurology Subacute meningoencephalitis in a subset of patients with AD after A1542 immunization Baclground 39 a srr A PM I l n tolembility of muliiple injeciions of aggregated A1342 AN1792 with Q5721 as adjuvant Methods 39 39 39 n 39 39 Minjections of m m r39 39 39 1 3 o 9 A 39 Hsafety tolembility and pilot ef cacy study 39 39 39 r quot r 39 antes remains blinded and further results will be reported after its termination Remus with AN1792 compared with 0 of 74 on placebo p 0020 Sixteen of the 18 had received two doses one had ieceived one do r 1 s r t r r s r r 39 A quotLA M7 last injecu39ons to symptoms was 75 and 40 days v I T A alive to date December31 2002 o morrtlrs to gt1 year after symptom onset F n lui n 39 39 39 39 safer arruzAls immunothenpy for AD MCDB 77 47775 7 Mo ecu ar Neurobwo ogy Lecture 16 Sensory mechamsmsr more mechanorecepuon paw ram 5 m the b Rewew mechanuvecEmuvs RewewvecEWe new 241mm mscnmmahun Pmpnuceptms and WW pusuun Mechanusensuw Pathwavs cavan Murmauun m me mam oumcax vEpresmalmn uVsnmmsensmv Wu Mm mm 3113533 3 an mmmm mm vlm s mu p smsmm 71w m 1 sn u us TABLE 91 A onmsymms and TheirProporties mm m k gt quot 39 39 i 7 Plain v sewnmm Slowly adapting Rt mmmi mm mpui w r mm mamme mu um i in Time s 39 neunosasuce Fourth Edition ml 942 wmmzmmu u Figure 9 6 Simulated activity patterns in di erent mechanosensory afferents as Braille is read Figure 9 3 Receptive elds and twopoint discrimination threshold lPart 1 A may Row of receptors on a nger moving across a row of raised Braille lelters il39 lj l l Merkel s disc 1 clquot a O39 391 Spike rate W lt7 n manna m NEUROSCIENCE Fourth Edmon Flynn 33 Pin 1 NEUROSCIENCE Fourth Edition Flynn 96 Figure 93 Receptive elds and twopoint discrimination threshold Part 2 Figure 91 Somatosensory afferents convey information 39om skin surface to central circuits Part 2 B Dorsal root ganglion cells Medlanosensory afferent fiber Receptor endings Pain and temperature afferent fiber 0510152025303 4550 can twopoint discrimination threshold mm NEUROSCIENCE Fourth Edition Flame 9 Fun 2 amw K NEUROSCIENCE Fourth Edition Figure 21 Part 2 m K Box 0 Dermatomes Figure 97 Proprioceptors provide information about the posit n ofbody parts A Muscle spindle Am of B Golgi tendon organ or motor neumn Trigeminal nerve branches lntrafusal muscle fiber Sacral Lumbar Extrafusnl l Thoracic Cervical USde bers Axons of 7 motor Capsule connectiv Group land 11 afferent axons usunoscrsuce Fourth Edition Flgun 97 MW K 85 A muscle spindle and several extrafusal muscle bers Axun of Axons of a motor Extrafusal Y momquot Group land II neuron muscle bers neurons afferent axons lntmfusal Nuclear Subcapsular Nuclear Capsule bag fiber surrounding muscle fibers chainfiber space spindle mun mumu L M TABLE 1 nunma mm In Senson funnim Magnum Am axon type disarmquot velocity um Myrna II deI Mrlkd Meiwill Mullquot u 5 12 um 3375 this and Ru lnl culls Winn Muscle wlmuo All in palm FM mcm np H im 530 ml A5 m xmpmxm ch Fm mmdlng 122 15 inn 053 ml c u quota Mn 4 m m mm M l WWWnu m l l u ule allnl ux uml L M m m quotN39Axualy nh l m mm w imam mnun I lmm RmmnuimI 4 NEUROSCIENCE Fourth Edition TIMI 91 vmq r The Golgi tend rgan Tendon bundles Organ of Golgi showing rami cation of m brik 1 user bera Figure 8 Schematic representa ays Part 1 A Cerebrum Primary somatic sensory cortex Midb in Ventral puslerior lateral nucleus of e thalamus Medial lemniscu Midpans Medial lemru39scus Gracilc nucleus arcuale fibers Cuneate nucleus Gracile tract quot Cuneale tract 4 Mechanusensnry receptors Cervical spinal cord from upper o y Lumbar spinal quot Mechanosensory receptors card 5 from lower body NEUROSCIENCE Fourth Eamon Figure 98 Pan 1 mm K Figure 98 Schematic representation ofthe main mechanosensory pathways Part 2 Figure 9 9 Proprioceptive pathways for the upper and lower body To cerebellum and dorsal column nuclei Muscle spindle primary Cervical up 50d somatic spinal cord sensory cortex Ventral posterior Thoracic Dorsal medlal nuc Hus spinal cord spinocerebellar of thalamus tract Trigemrnal Iemnis Clark 5 nucleus Trigeminal Lumbar ganglion spinal cord lt Muscle spindle i A V afferenls lemniscus PnnuPal nucleus Mecmnmnm y Sacral km bad of trigeminal memo from face spinal cord complex NEUROSWENOE Fourth Edlu39on Figure 98 FIR 2 any x NEUROSCIENCE Fallth EdI oII Figure 99 vanWm K Figure 910 Somatic sensory portions ofthe thalamus and their cortical targets in postcentral gyrus Figure 9 11 Somatotopic order in the human primary somatic sensory cortex w Primar somatic Somatic sensory sensory cortex SI cortex osterior r I parietal cortex 12me mm 51 I I nstcentral Central 5 gyrus 41 mi Ventral posterior medial nucleus VPM Thalamus Secondary somatic sensor cortex 39 m 5 Y Ventralpostennr Egrm lateral nucleus VPL VP complex NEUROSCIENCE Fourth Edlh39on Flynn 910 umzmu m K NEUROSCIENCE Fourth Edniun Flame 911 m 4 Figure 913 Neurons in the primary somatosensory cortex form functionally distinct columns Figure 914 Changes in somatic sensory cortex of an owl monkey following amputation ofa digit I A Owl monkey brain 1A I nmmal Mum Somntic sensory cortex Hand representation C Hand representation two months after K k I I i r gum B Normal hand representation digit 3 amputation ivrpaw Caudal amu K NEUROSCIENCE Fourth Edmon Figure 914 www3 K NEUROSCIENCE Fourth Edm39on Flynn 913 Figure 9 5 Functional expan ofa cortical representation by a repet ve behavioral task B C Before differential After differential stimulation stimulation NEUROSCIENCE Fourth Edl on Flame 115 MCDB 47775777 Mo ecma New wa Wha ave me mam mmmuw nemmvanwmem Lecture 13 Avemev aways mmmtum Synapse mechamsme me Hch dwersm of neurotransmmers and mew receptors Huwave thev phavmacmumcaw mpunam Wha ave me amne vansmmevsv Huwsn heslzew Huw mmwem Huwave thev phavmacmumcaw mpunam E V lt m m m E AV xvmwnwr 5 4 39usmhnuw lnhxhnnlv v mmmm E E Ewmmu 2 E 0H E hudy e s ltm u 33 100 ISO 5u an 33 m znn Ti me In 68 Synthesis release and reuptake of GABA 69 lonotropic GABA receptors Part 2 A a W B Benzndiazepinc r Presynaptic terminal From Vitamin B6 Picroloxin Postsynaptic all C A BA rcceplurs uWnMauapuuw u u m i Wulunlnpmn Km l Box 6D Excitatory Actions of GABA in the Developing Brain 64 The general architecture of ligandgated receptors Part 2 bnminrv m unm MMLAW ruuml w dab Owrdd 39 C mu I lLma I 2 g in mM ici l n n s m l 2 1s NEUROSCIENCE Fourth Edition Box 6D Wmmmhm mm H 65 Structure and Jnction of metabotropic receptors Part 2 61 Examples of smallmolecule and peptide neurotransmitters Part 1 SMALLMOLECULE NEUROTRANSMHTERS l 1 mmmmnma em Wmmv numu m u 68 Synthesis release and reuptake ofglycine Part 2 61 Examples of smallmolecule and peptide neurotransmitters Part 2 B SMALL MOLECU LE NEUROTRANSMTITERS g gartic PURINES BIB2 ATP N N 111 I O Il O ll O Il O CH2 O N N 039 Oquot H H OH CH C yci ne receptors Postsynaphc cell mmmwuwnewmu w mun mumaemm 64 The general architecture of ligandgated receptors Part 2 61 Examples of smallmolecule and peptide neurotransmitters Part 4 SMALLMOLECULE NEUROTRANSMITI39ERS BIOGENXC AMINES INDOLEAMIN E Serotonin 5HT fMIDAZOLEAMlNE Histamine HO 7 a irm239m2 NH A HN N N CHI CHg mIs 61 Examples of smallmolecule and peptide neurotransmitters Part 3 SMALLMOLECULE BXOGENIC AMINES 0H Nurepinephrin HO OH OH Epinephrine Wmmupmwn alumna r r Tyrosine cow mun CH as xv 0 Tymzne hydruxylasc Dihydroxyphunyialanine m Heg1 i DOPA quotf no 0H DOPA a ducavbnryiaw Dopamine a RibMANN UH r Dupmn i III i hnl rmvlasc W mam m Wu Emu L NEUROTRANSMTI39I39ERS CATECHOLAMINES Dopamine CH1 tug 191 HO Gin cH cn Km H CH clay rim CH mmumzamw ummmh ww 610 The biosynthetic pathway for the catecholamine neurotransmitters N 39 V I nrepmephnne T H cu 704 NH rm OH Piicnylulhmmlaminc it Nmulhyitunsl crasc on Epinephrine n Cll39OI VIL no OH man Mm m m Wur 1 Distributi of neur ns amp projections co A Dopamine Cerebral co rtex V Cerebellttm Substan a nigra Pons 1390 spinal and ventral cord tegmenlal area wmmmr eu vwwn m Amine release and removal Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A 39 H G Brunner M Nelen X 0 Breake eld H H Ropers B A van Oost are enacted by a syndrome of bordenlne mental retardation and abnormal behavior The 39 L r 39 u 391quot axhihlttnnlem A h Mm L 39 39 mm r r a metabolism This syndrome was mociated with a complete and selective de ciency of 39 It I anm I 39 nminl M mutation was Identi ed in the eighth exon of the MAOA structural gene which changes a Thus r quot mu tarnin yawn 01 Impulsive aggression Amine release and removal mat t m we mm Flutr IEJI Dwtlmmetglt synapse Yllc eyntlluttc ster lmm x osme In DOF39A t hl 1411 re a mum to we xtetlnt ul moxmnwxixtm mums tum 0A to Ulnyutotv phenylaueitt aciuDDPAC MM when 39 an by g imln a Btvue m l tlmm l um mo i 3 E g E 2 I m VI amtetrabenazina acnaseqnemmnmm Kl I DA gets back me me mm Awwmhme D a Watuncut B if 939 I u mwr magmas at the wstsmnllc mama ramming mocks lhe pastsmaprz aclnn m Malawipt it com Amine release and removal SUEVVKE ZAugust ZDO lt Prev table at Contents Next gt 2 Vol 257 mm 5532 pp 851 554 DOI IDtIiZSsuencc 1072280 REPORTS Role of Genotype in the Cycle of Violence in Maltreated Children Avshalorn Caspi139 2 Joseph McClayI Terrie E Muf n 239 Jonathan Mill1 Judy Martin3 Ian W Craigl Alan Tayictrl Richie Poulton conferring high levels of MAOA expression were less likely to develop antisocial problems These findings may partly explain why not all victims of maltreatment grow up to Victtmize others and they prowde epidemiological evidence that genotypes an moderate hildren39s senslttvity to environmental insults 65 Structure and Jnction ofmetabotropic receptors Part 2 Manama awn emmn Amine release and removal mm km A we wry W K Vim LWA I39m Flum 1521 WMME synapse quoti8 ymnw u hum n1 0 DW 5 by MMms m M m a WMMIWE mmw oi lyrlwne ny mlyiasa The 39Ml39i39l W DA Is mm by m tMIbI mm mm Tm soq 0 0 mobs Li Mm by ramming m I Da lma Mm m M 390 I0 l I mm by an and 1 m ruran i l 34 ms Win nmllmi TM 1mm ui DA no rm or ii pol mm pro nw Dom MT in unit 3111va Whlhminn r am WW I quotE A hid min the prawn91h humL We mi Immune blank menumainquot mm DA 915 baa mm In lemma mum sum9min momma ampu mmwu r P and manual m iiwumrEmxm am at the mime Mame rmmmimpmmpkmmm Podnamed mm 611 Distribution of neurons amp projections containing catecholamine neurotransmitters iF an 2i B Norepimph ne Corpus callosum Cerebral C rte Cerebellum To spinal Medulla cord Wmmmnumwemw C Epinephrine Cerebral Cerebellum H ypothalam us Medullary Medulla To Spinal epinephrine cor neu rum mmm wmmn mam 613 Synthesis of histamine and serotonin 612 A Distribution ofneurons and their projections containing histamine A ml B A Histamine Hisljdine Tryptophan 100 l Corpus caliosum 39 39lL Cll Vll m h WWW VIM Cerebral 39 V 3939 V cortex Nialldiliu dcmrhuxyias c m 02 Tr pmplmni Histamine H hydmxylaw IZFcIi cniNn lt I IN N 5Hydmxytryptophan W V Ho 1 I man ml Nm N 3 Alum it iaminu acid dccnrlmxylnsv 33 Serotonin 5HT no Cerebellum H I rm wt N mmmnnauynuu umi V To spinal co rd Wamrwum u u awn Medulla 612 Distribution ofneurons and their projections containing serotonin B Serotonin n Corpus callosum Cerebellum To spinal Medulla cord MWMmrwHHMH m mm c MCDB 47775777 Mo ecu ar Neurobwo ogy Lecture 15 Sensory mechamsmsr me somatosensory system 1mm antpmtphdne m 7 k 7 u T quot mt Nwmh hmmhu 7 MW mum mumquot 7 L w cum mm L V swmmarmmmex 139ch he mi c m Nm K Wl 397339553113L 55 Metabolism of smallmolecule and peptide transmitters Part 4 CB1 cannabinoid receptor expression 79 Mechanism of activation ofprotein kinases Part 2 79 Mechanism of activation ofprotein kinases Part 3 C I KC Bl CaMKll I39lmsplwry substrates a ms Active Regulatory Catalytic domain dumam phosphmylalg subslrates Catalytic Regulatory domain domain 710 Steps involved in transcription of DNA into RNA 711 Transcriptional regulation by CREB A Chromosome B Beadefmyaak ngdtmma n UAS quotMann ona l l activator pmh ein U Coach vat nr compl x 39 I 1 smAponmm gt and associatedfa tors U As yahrtsaceormix Coma chromatm mmmnumww mmmmnm 712 Mechanism of action of NGF 713 Signaling at cerebellar parallel ber synapses Iquot 39 h i mmnmm Wmmm1uemhm gt1 Box 7B1 Dendn39tic Spines Part 1 NEUROSCIENCE Fourth Edlh39on Box 73 1 Par 1 Box 7B2 D VII LK mum NEUROSCIENCE Fourth Edl nn Box 13 2 Box 7B1 Dendn39tic Spines Part 2 B C Dendrile 39 i resvnapiic i im 1 lerm 1 l nsLsynaptic Spin density neck Spine Spine head 1 pm NEUROSCIENCE Fourth Edition Box 78 1 Pan 2 83 The skin harbors a variety ofmorphologically distinct mechanoreceptors lipidernm Dennis Path 1 1H Ruf ni x Mrrkel s des corpuwlv muscles Fm nurvc endi I1glt Stimulus Slowly adapting Rapidly adapting 0 1 2 3 4 Time s wnmzmmu em mm a LE 51 m MaMOa siotSonmk nwgy animus Phall mama WI War AlumW Wm walnut R1140 Wald mm mm 731105116 Dalian W Malian afadh iau mm What A Quad km 5m 15 mm H mm 7 M Hum gt my Hum lllhdjl39 quotId We mm um was What I39m stiltFM Frans5 vialmu immi m lb Tllll l i Mm aw um aga mand mu analputs Isa my m lampsmm m tum my W w m um nu um um w 4 mum new mm huhmum Amtha m M rutAmquot ulna mm mm quotmm m mm In x n MJC A mm uquot mm launuunnfilw walk HM Ilene Mn mem Mm uu mm m A liar aw I min huhu mm mxinur mp W n m aluml m r m lxml u m IIIhm mm mm monk mmu mvl n m z y y apnun m w mm ou Imp l uh mum n quotL m w Ilw kh qlrnllh bumup assignml m mm maul1h mmmunm mn rA LE all 1h Ma dgssasoismlk Sensory Manors Pauli Modi ed Mind mmhf39 w Knowquot Mimlq39 mamain 31quot MW type dammitquot dim was mum Emlyn mlaErunv uE uMm m Hum mamu chi mm sum 9 sum m m gearHad 7 renewal Mind mm muralm An Nayu M m39 m wild luwmx sum rs1 l l Mum M in quot1quot 1 1quot will Main Main Emaunfet M VII13 m w lurk H Lk 17 1 mm M in mm m m my Mum M1 mm mm quotarmhm m m mm mm mm nihl A n 4 c i m m m w m M c m mum in u WWW m mu ml mn Wm A n iw W W m mquot Wm m mm 1 in A w l m mm WWWkn m m mm Wuhan m m mull mum ml in mum NH m mi u L mi w 4in m l Wm WM m Mm quotmum Wmmmumilnmwnwn Variation in sensItIVIty of tactile discrimination as a funct body surface g g USIUIS 253035404550 Two palm discrimination threshold mm meluemy A n un MCDB 47775777 Mo ecu ar Neurobwo ogy Lecture 20 Senso y mewamgmg39 cewa V Sua proceSSW Reunumpv mmewsua waemandme cunsequencesu esmns R39wewwsua mucessngmusm RGC was mme mam and memnmun mmese pvumctmns LGN and cumua veceMNe new pvupemes Pmcessmu m dmevem ca Egunes mvwsua mmvmauun Gunman when ma NamImmnf aquot rum41 mu m a 1019 Circuitry for generating receptive eld surround of an oncenter retinal ganglion cell Part 1 A avquot Surround Center iSunound Red arrows GABA release Surmund sign conserving synapse CUM39 sign inverting synapse amp Center cone o H zonla Relative Intensity of cell illumination is determined P at the rst synapse l Onvccnter f ganglion cell hm sz w Aqueous humor in anterior chamber ostcriur chamber Optic disk Oplic nerve and relinal vessels KWIMMM lbwIii m an a 1017 Responses ofoncenter ganglion cells distributed across a lightdark edge Dark Edge V Light Response rate Pusi lion KWlnwu Iwnnu 1 112 Central projections of retinal ganglion cells Optic Oplic tract nerve Optic Hypothalamns chiasm Lateral geniculale Preteclum nucleus Optic radiation Superior colliculus Striate cortex Inwame MM nquot ma 5 113 The circuitry responsible for the pupillary light re ex Part 1 114 Projection of the visual elds onto the lelt and right retinas Part 1 A um um 7 an ganglle I tl39gnnginlnlt wme 39c rplml uuclt ua l3 Binocular visual field Pvtwant Supenm mmmm Monocular portion Monocular portion of visual field of visual field W Left visual Right visual field field Wu mmquot o n u no r V 114 Projection of the visual elds onto the lelt and right retinas Part 2 115 Projection of the binocular eld of view onto the two retinas Left monocular visual field Right monocular visual field Binoctllar Visui l l i ld Superior S 5 Right visual field Temporal Nasal T T N Fixation inferior l Pmnt l Left retina Ri t retina S 5 sh mume n IIMM mung undome Mr 5 m woicr 116 Visuotopic organization ofthe striate cortex in the right occipital lobe Part 1 117 Course ofthe optic radiation to the striate cortex A 1 oral Fibers representing palgem0ccipna ventricles superior retina quicus quadrants Binocular Mamla Calcarine portion 39 sulcus Monocular em Fibers representing ortion geniculage inferior retinal Left visual field nucleus Q dems Meyer 5 loop Right occipital lobe lmmw39vunw u an 5 Kuwame MM nquot m hm 118 Visual eld de cits resulting 39om damage at points along the primary visual pathway 1110 Mixing ofthe pathways from the two eyes rst occurs in the striate cortex Part 1 f eyc Right Le t 39 eye A Latch geniculalc nucleus Srrimc cortex visual field visual field A B 9 5 9 C Latem I i geniculatu D nucleus 39 39 Optic E radiation i r Striatc cortex Winum w Iu nu wnna um mwwwunu m u m 2 1110 Mixing ofthe pathways from the two eyes rst occurs in the striate cortex Part 2 119 Neurons in the primary visual cortex respond selectively to oriented edges A Experimental setup B Stimulus Stimulus orientalion presented H Light bar stimulus projectud un screen Recording from visual cortex ll lllllll N ll 139 I E I ll Parieto Calcarine Posterior occ1p1tal sulcus poleo n 1 2 3 sulcus 0cc1p1tal lobe mm 5 MCDB 47775777 Mo ecu ar Neurobwo ogy Lecture 21 Sensory mechamsme Rocks w your head 02mm aummw pvucessmu Lucauzauun m suund Vemmav Mam me senilry ceHs and mewmncnune mum Umans and semmwcmav cana s 02mm curmemuns and mums ve a edmme ves1mmaVSs12m a jaqumgm 2 9 Mechanoelectrical transduction mediated by vestibular hair cells Part 1 129 Mechanoelectrlcal transduction mediated by vestibular hair cells Part 3 A Displacement putantials mV Receptor Time u m 70 U ltl 20 30 40 5 Time ms mmmmr mm H m ham H 121 Response properties ofauditory nerve bers Part 3 1211 Response properties ofauditory nerve bers Part I A A20 Spikessecond 01 10 100 leuluency mm munu munm nu mu m n it umumu mmu n i n no out V 1211 Response properties ofauditory nerve bers Part 2 B Frequency kHz 01 10 100 membrane Box 0 Sensorineural Hearing Loss and Cochlear Implants Part2 Auditory ummrmunu m cm cymbal Box 0 Sensorineural Hearing Loss and Cochlear Implants Part 1 Microphone Implantable cod ilear stimulator Headpiece Cable to speech processor lmmml ncn m cpm u ma Am 1212 Diagram ofthe major auditory pathways Cerebrum Primary cortex Medial geniculatt complex of the thalamus 39 1 interior collimlus Caudal midbrain 39 Ponsmidhmin junction 39 I Rostral midbrain Mid39Pm S Superior olive Cochlear nuclei Rosrral medulla Posteroventral Antcroventral Wymammuuum k c 2 1 Response prouerties ofauditory nerve bers Part 3 1213 How the M80 computes the location of a sound by interaulal time differences g Loudspeaker C 39u E 0 U 0 ll m m x vrI a m leading neuron Right ear Shorter path gt Cochlea and cochlear nucleus memvmwmmw nammbmpm u mum Figure 13 14 L50 neurons encode sound location through Interaural Intensity di erences Wm 17 Figure 125 14 L30 neurons encode sound location through intelaural intensity differences Part 2 E A Speaker Net excitation to highercenters Net inhibition v 39 MNTB Output of LSD 70 4O 20 0 20 4O 70 Left gt right Right gt left Relative loudness NEUROSCIENCE Fourth Edition Flynn 1314 Pan 1 exam m x NEUROSCIENCE Four Eamon Finnquot 1amp14 Part 21 Figure 1315 The human auditory cortex Box A A Primer on Vestibular Navigation L unnpnmb m L39 nunmu m up or him tmw or him Yaw Rotation around 2 axis 2 4quot uudllury mrlm mm mm l m quml Mun Wm 1 Ram lwmuptwlv hum mlmn m Pitch Rotation around y axis brunch mu S quot quot an Audll tlzv avian mamw man v Vunuzwum Lawmmw NEUROSCIENCE Four Edlh on Flyuro 1315 mmMI umnuulun amendquot 124 The cochlea viewed faceon and in cross section Part 1 131 The labyrinth and its innervation COChIea Endolymphatic Ampullae 5c pa s Vestibular part duct ganglion of cranial nerve Vlll Auditor 39 y b 39 Facial nerve nerve Auditory part of cranial nerve I l Can muniens mmxcmisahrvn mm H an MA Wmmmrlamun u 132 Polarization maps ofvestibular organs Part 2 134 Morphological polarization ofhair cells in the utricular and saccular maculae Part 2 Ampulla of superior canal 39 mamla Ulriculnr macula Saccular macula Superior Anterior Striola Medial Ulrrcular Inacula Saccular macula Lateral l Posterior Srnola ntunor Ampulla Sacculus Utricle W mu Kymmava mum Immith Min lwnl nlr m Mam 132 Morphological polarization ofvestibular hair cells Part 1 134 Morphological polarization ofhair cells in the utricular and saccular maculae Part1 A Striola A Crosssectional View B Top View Olmoma I V Otnlithic membrane DII ECUOIquot of depolarlzmg de ection gelatinous layer Relicular membrane Kinncrlium Stcreodlia Supporting cells Haircells 5L 4 z zl B Static till 7 LJYIL KL bers KW mun ryevulvaquot mum m 135 Forces acting on the head and the displacement ofthe otolithic membrane 133 SEM ofcalcium carbonate crystals otoconia in the utncular macula of the cat Head tilt sustained Upright Backward Forward No head tilt transient Forward acceleration Dcceleration W Minmm mh 136 Response ofa vestibular nerve axon from an otolith organ Part 1 138 Functional organization of the semicircular canals Part 2 Right Left anterior anterior canal AC canal AC mmmnmrwmmn m yumquot Illsclmrgv rah kpikrsm n w an ill mm M 137 The ampulla ofthe posterior semicircular canal 138 Functional organization of the semicircular canals Part 1 B Cupula displacement Angular acceleration I Semicircular Hair cclls canal Mcmbranous duct Nerve bers Imusurqu ma h r Wmmurymmu m Box 0 Throwing Cold Water on the Vestibular System Part 1 139 Response ofa vestibular nerve axon from the semicircular canal to acceleration A Lch horizontal Right horizontal canal nal Head toms Ampullac Axis of hair cells Body Fluid molion in hnn znnlal ducts Afferent bers Aferent fibers of nerve VIII of nerve Vlll Discharge rate spikes s Increase n Decrease in A 40 80 firing ring Time s ummmmmuucmuzmn awnmugquot nu44mm 1310 Connections underlying the vestibuloocular re ex tum head to le eyes move right 1311 Projections 39om medial amp lateral vestibular nuclei to spinal cord underlie VCR amp VSR Right eye Left a e M d al Y I I c I 42 1 pg t Laleral rectus rectu A Lateral vestibular nuc eus VSR vestibulo spinal re ex Oculnmotor otolith info to spinal cord nucleus k W 7 Cembellum Midbrain MidJ ons Medial vestibular Fons Medial longitudinal quotUdcus laSCimluquot 1105quot medulla VCR vestibulocervical re ex 39 semicircular canal info to Abducer s quotUdeus Medial longitudinal ulpperc e icalspinalcord fasciculus l Lam V95quot W Sca a39s an lion 739 5 im tract m g g Medial vestibulo P spinal tract Rostral 39 r S l d Edull39 Medial vestibular 1quot mquot nucleus 3t Ventral horn WWII VIquot 10 rlux nu Wmlmrgnnll Kym AM 1312 Thalamocortical pathways carrying vestibular information Posterior parietal Vestibular max cortex Region near face representation of Si Cerebrum Lateral and superior vestibular nuclei Pans I L Mmmvuuwuu an N MCDB 47775777 Mo ecu ar Neurobwo ogy Lecture 25 Lower motor COHUO muum mum mm Muluvpumsand mmmums Gamma 7mm neuvuns and Spmme ve zxes Gumuendun umans and mama mums Hana bevs and mm ve zxes Panequot genevaluvs Law mmm neumn msease Figure 162 Spatial distribution oflower motor neurons in the ventral horn of the spinal cord B C Medial gastmcnemius in ctinn Ventral horn Lower motor neurons ammuux quotsumac Fourth Edition Figure 132 Figure 165 The motor unit A Muscle bers innervated by a single motor neuron noun m Figure 163 Somatotopic organization of lower motor neurons NEUROSCIENCE Fourth Ednim Flgun 163 Figure 166 The force and fatigabilit39y of the three different types ofmotor units A Calm 01 mar NEUROSCIENCE Foamy Eamon name 135 awn K mg Figuie 16 7 Motorneuron recruitment In a cat muscle under di erent behavioral conditions Figure 16 4 Location of local circuit neurons that supplythe medial region ofthe ventral hoin Cummissural axons 30 Longdistance a local circuit g neurons Fast E 50 fa gable E x m E E 40 E 1 Shortdistance 20 39 Fast local circuit V 39 fatigue neurons resistant 0 SIOW Motor nuclei 25 50 75 00 to limb muscles Percent of motor neuron pool recruited Motor nuclei lo axial muscles NEUROSNENCE Foam Edmon Flwn 157 anluu x NEUROSCIENCE Four Edmon Finn i Bme x 15 I Overall organization of neural structures involved in the control of movement Figure 16 8 The effect of stimulation rate on muscle tension SPINAL CORD AND BRAINSTEM CIRCUITS NEUROSCIENCE Follth EdI OII Flgun 168 Maw K me ynul umva Figure 1610 Stretch re ex circuitry Figure 1610 Stretch re ex circuitry Part 1 my A Muscle spindle NEUROSCIENIE Foam Edition Flgun 16 mun K NEUROSCIENCE Fourth Ednim Figur 1s1o Pan 1 mquot Figure 1610 Stretch re ex circuitry Part 2 Figure 1610 Stretch re ex circuitry Part 3 5 1 Motor C neur Muscle spindle Homonymous muscle Increase spindle afferent discharge NEUROSWENCE Fourth Edithquot Flynn IGJO FIR 2 NEUROSCIENCE Four Eamon Flgun 1610 Part 3 emum x Figure 1611 1 motor neuron activity regulates muscle spindle responses Figure 1612 The function ofmuscle spindles and Golgi tendon organs Part 1 mi 41 Mottr mum dchvaIun mumn y m a Murat mumn acln allun mm 7 A Extmlml usdt lntmlwA muscle ll m ftch fibers Capsule Sumuan 11 main mama Stimulate u mutm mum V Spindlv lb afferent Allt39nml neurun Stimulant I mom quotMIRquot V n GT0 Ian on llcdin quotl39 Collagen Muscle Musclt l brils lmn hm v j Tendon L mtmnm Contraction quotll i i p NEUROSCIENCE Fourth Edition Figure 1811 m m K NEUROSCIENCE Fourth Edition Figure 1312 Part 1 mung Figure 1612 The function ofmuscle spindles and Golgi tendon organs Part 2 Figure 1612 The function ofmuscle spindles and Golgi tendon organs Part 3 B MUSCLE PASSIVELY STRETCHED MUSCLE ACTIVELY CONTRACTED 1 Muscle spindles Z Golgi tendon organs 1 Muscle spindles 2 Golgi tendon organs MuSdE famed Muxle summed Muscle contracted Muscle contracted 39 Extrafusal muaf lsal El m 19 muscle fibers fibers Stimulate a motor neuron Spindle Golgi Spindle Golgi afferent tendon afferent Golg tendon organ tendon organ afferent 33 afferent Afferent activity Afferent Afferent activity an activity 1 Stretch M 1 length lengd NEUROSCIENCE Fourth Edln39on Flynn 1612 Part 2 NEUROSCIENCE Fourth Edition Figure 1612 Part 3 Figure 1613 Negative feedback regulation of muscle tension by Golgi tendon organs Figure 1614 Spinal cord circuitry responsible forthe exioncrossed extension re ex riding Ib afferent lb inhibitory Cutaneous afferent fiber intcmoumn quot v iur A5 esce pathways i39rom uncut l Mutnr neuron 3 39 neii ron Flcxur muscle Extensor musclu rri Exiensnr xtensor muscle muscle Stimulated lug Opiwsik 10 flexes to withdraw L Kk nds m 39 support Cutanumis roccplur NEUROSCIENCE Fnu h Edition Figum 1813 NEUROSCIENCE Fourth Edl nn Figure 1814 Figure 1 15 Gen pattern generators in terrestrial mammals ower motor neur n 5y M 537 a e Ef iQ ii MthMl quot Amyotrophic Lateral Sclerosis a F Ei I3 I I 7 J i M quot 005in USA mm W I I MW Fatal Within 35yrs usually mm quotmayquot respiratory failure mi it mm liq mull Degeneration of or motor neurons Paralysis and paresis Loss of muscle tone atrophy 10 familial 20 of these are mutations in superoxide dismutase Molecular cause uncertain axonal transport m NEUROSCIENCE Fourth Edlh39on Flgum 1815 A km MCDB 77 1 ectoderm gt neural 47775 7 Moiecuiar Neurobioiogy Lecture 33 2 generation migration ofneurons and giia Neurai Deveiopment tropnic interactions criticai periods a speci cation orparticuiar ceii rates 4 axonal and dendritic path nding 5 rormati on of synaptic connections 6 activity dependent competitive reorganization of connections 7 ongoing synaptic piasticitytnrougnout life Anatomy of a neuron ovai of a hmb bud causes the death or rescues neurons motor and sensory normaHy rated to die neurons 1222 n mmmmm Neumns umpete rura men supp y ur sunwax facturs Wmners We and users we 2213 The in uence of neurotrophins Part 1 2213 The in uence of neurotrophins Part 2 ii Dorsal mut gangliun S I 1 muscle 39 Pilld mm 5 ndle mums11w Mer W y mm H Box D The Discovery ofBDNF and the Neurotophin Famin maneuver vmulmlwunuuyui 2214 Evidence that NGF can in uence neunte growth by local action Ix aurl supdrdling mmpartnwmi A B and C Nuuritu rc x Kcup NGF m 39mnpnrlImni cmm cd v AandB Q B Well ii mmwm mm n1 39Lll A Well C No NGF Nu NGF NGF mumquotW mum e u 2215 Neurotrophin receptors and their speci city for the neurotrophins 2216 Signaling through the neurotrophins and their receptors mnhhmuntmwu mh mMm mnInmmm w Box A BuiltIn Behaviors A Gangiion cells B Muscle cells Initially multiple axons synapse with each postsynaptic cell At birth Subsequently these exuberant connections 39are refined In maturity WummmauumAu a Box B Birdsong Part1 Box B Birdsong Part 2 A Cl Bl Sta n ZU 3i ulll Sll 6 70 Si lll lLlU l 1U Iimu days 15 1mm gtl MMm nwl mum 2m m mm unmvscimrr mm a u m mm H i 232 Learning language 231 Manual quotbabblingquot in deaf and hearing i fants 00 O Deaf A l 391 Focal l3 ants activated differences 5quot 0 Link run agu 7 l 40 Lg j Native 3 710 llilh 1773 speaker Agc of arrival yeah 20 Adu I I5 Manual babbling quot0 manual activity 9 10 11 12 13 i4 157 Agemonths mmunnmmmwum i quotmumyw 233 Ocular dominance columns in layer IV ofthe primary visual cortex ofa macaque Part1 Cortical layers l llI OPUC radiation Lateral geniculate Optic 0pm nucleus nerve tract quotWm mum r1 mum it 233 Ocular dominance columns in layer IV ofthe primary visual cortex ofa macaque Part 2 quotmarlx1 1711mm Fwn mm t Box 0 Transneuronal Labeling with Radioactive Amino Acids Retina Thalamus Cortex Labeled Terminal Terminal amino acids labeling labeling Antumgmdu Antomgmdt axnnal dXthl transpurt Transnemonal transport transport 5 Q gm 5 aquot 1 into proteins mm mummy1 am Effect of monocular deprivation on ocular dominance in kittens v adult cats iii Mumu nlurdvrnuutm mum Figure 244 my ximmmnm my Minunultu tlt39pnt39uliun mklllmt g Q azaleas a Ipvrluwm 39 I mumm I mmm nmm mm mm mm mum mm pmumw tatmmquot i E mmrm u Htrtmttm u m 3s 0 l y cmumn Wm umtmt quotmum autumn Munm hlnII gt lt tqtu gt lt trm u 97 114lt Utuhr v dunnnnnu l I l I rv Ii1lu1 E g NEUROSCIENCE Fourth Edition Figuquot 2amp4 7 R I I I E nlu mm Figure 245 Effect of short period of monocular deprivation at height of critical period in cat Part 2 236 Effect ofmonocular deprivation on ocular dominance columns in the macaque monkey Bl Birth Experiment S 0 l 2 months h days monocular deprivation A 8 5 Number of cells E J 2 J 4 5 h 7 Cnntrnlateml lpsilaleml lt Equal gt Ocular dominance grou Monoc depnv open eye injected w quot Q radiolabeled aa s NEUROSCIENCE Fnurlh Edition Figun 245 Fan 21 WA u wmtlmuvmmnwuul u m 237 Terminal arborizations of LGN axons in the visual cortex can change rapidly Figure 249 Testing Hebb39s Postulate by inducing strabismus A Normal B Strabismic A Shorticrm monoculardeprivation B lungterm nnmoculardeprivation Q a Open eye m Open eye 60 if 39 quot 39 HIV 7 E 40 z 5 20 gmquot l234567 1234567 UHHHJHCE group Cuntralatuml lpsilalcml Contralnteml lpsdatcral 4 Equnl gt 4 Equal gt NEUROSCIENCE Fourth Edition Figum 249 e 4 Mmmwtmvwiun Mm n T 24 1 Critital Periods and Molecular Ragulators for Some Neural Systems tidal Med Sysmn Spudes39 postnatal Neummusa nr umion Manse Pam tn day 12 S renglhming Cmbellum m 091515 NMm IuGlan cf PLCB PKQ 0139s quot3 595 laxignl ulmm Mm mnm Prbrlodiy m AOIAMP MAOA N0MHCLCREB 939 quot91quot Wardnmimnce Cal m m Sweeme GAMWM PKA mumm I m out rarer BDNF nu moldquot aynlhcsu Nam PENN Cabmm Mono 2 NR NRMJ SDES Sommmnsmy may Mouse rat Prlor to day 7 15 Ngapr mon 5H1 cAMBmGlIRi PLCBl Right anpicmap lmn39ex Ki Days 1550 m we AhSOlIyL pitch Human Baton 7 mm Unknown I 1am olfac nn Maui Nuns GABl mclukz Mo Weds lmpn xid g Bud 1441 luxns Catecholmh vs Slim mxiety Rat ms Prlnrm day 21 Homes SH39I39M SlowWe amp 41 mm Day 40 60 NMDA Layer IV cell Sound lualm m Bamawl Pdnrlndnyzm NMDA Maw Zahaan Friar Indny 100 GABA Manama Mumgends Language Human 0 12 years Unknown l nmmv my 1mm m dunme u mulu ulquot Mumm n l m qu um ll Im NEUROSCIENCE Fourth Edition 139th 241 Figure 2 10 Trans of elec cal ac NEUROSCIENCE Fourth Edition Flgure 3410 MCDB 77 1 ectoderm gt neural 47775 7 Molecular Neurobiology Lecture 31 2 generation migration ofneurons and glia Neural Development Wiring it upi a speci cation orparticular cell rates 4 axonal and dendritic path nding 5 rormati on of synaptic connections 6 activity dependent competitive reorganization of connections 7 ongoing synaptic plasticitytnrougnout life msalizing molecules BMPs in emnderm and rnnlplzle DnrsalinActivin in dnlszl NT 12 12 Nailanan ma mm newquot Box 22F Neurogenesis and Neuronal Birthdating Hinhdale unimm mapping NEUROSCIENCE Fourth Edition Box 22F Figure 2212 Radial migration in the developing cortex Part 1 B Pin surface Radial glial process Cortical 11m Rddm Radially glin migrating cu Vuntrlclc Nunradially ntermedi tE 10m migrating cell Ventricular 39 zone Radial glial cell body NEUROSCIENCE Fourth Edition Figum 2212 Pan 1 w Figure 228 Generation ofcortical neurons during the gestation ofa rhesus monkey Curtlml mes l lEQEDL T 39T quotl llF ll Lquot i ll ll l l q r V w i l W11 itc m ll 10 4n 9 llll 120 30 L Day at 1 1 II hymnlnu Injcclmn 1 lmmml nuumg wsb HU 150 lanmh p oi mum NEUROSCIENCE Fourth Edl 39on Figum 228 Figure 2212 Radial migration in the developing cortex Part 2 C Ruelin RLN Glinl onnll39mxt Leadng prucess at mm 7 Endnih bmnectin Nccmk L1 Migrating nuurun CDKSI39SS neumgulin Lisl DCX astroiaclin 2 receptor NMDARL q 5 integrin Trailing process NEUROSCIENCE Fourth Edition Flgure 2212 Pan 2 Box 22G Mixing It Up LongDistance Neuronal Migration Figure 2213 Mutations in genes that in uence neuronal migration cause malformations of the human cerebral cortex C Lisscncephaly DCX B Rn liu mulation A Nurmdl NEUROSCIENCE Fou h Edl nn Box 210 L 1 m a NEUROSCIENOE Founh Edilinn Figure 2213 Figure 22 11 Gene expression and cell cell signaling during neural crest development Part 2 Neural crest progenitor Figure 2211 Gene expression and cell cell signaling during neural crest development Part 1 Trigcminal ganglion Amustic an 7linn v r g b neurnn39 Sympathem Chromaffrn progenitor CL progenitor Aortic arches hmquot can My 1 e0 neuraa mphi L mm 2 factor Glucocnrticoids DRGS Neural lube Ad rcnorgic neu TUquot NEUROSCIENCE Fourth Edition Figurl 2211 Pan 2 NEUROSCIENCE Fourth Edition Figure 22quot Part 1 1A Needle with DNA sequenceita retroviruses that express Sgal ui liun 4nd unuly39lc think tnb llcmu l39ignmil upilllwlimn 2 possible outcomes to the viral lineage tracing experiment 1 daughter cells containing a given DNA sequence tag Will be part of groups having a particular set of fates indicating the presence of a committed precursor cell e g could see a cluster of photoreceptor cells only indicating the presence of a photoreceptor precursor a set of bipolar and amacn39nes indicating a bipolaramacn39ne precursor etc 2 no consistent grouping of cell fates den39ved from a precursor ie having the same DNA sequence tag Indicates that cell fates are entirely the result of signals on uncommitted precursors 1218 Create library of Iquot 39 A F n39 retroviruses having many different Variable seq PM kpho DNA sequence tags as well as enzyme for histochemical visualization of cells Injectvirus library during development Some progenitor cells infected Their daughters differentiate Result no clear evidence for speci c lineal relationships between precursors and speci c daughter cell types Thus cell cell interactions are critical Recall retroviruses only infect dividing cells Visualize cells using histochernical stain l Sequence DNA tags to identify members of a clone daughters of a progenitor Chrishiphzr a mum Subil r Tamuizz a cim39mpm A wand Develnpmentlu zmruiu 1997 Inthe emean rmng mdely Axan and aenume gumsnuer wrmg up he WWW am mmhn or Hum In Adu nrmu uh mm Anatomy of a neuron Mechanisms of Axon Pathfinding 1222 221 Basic structure ofthe growth cone Part 2 Figure 231 Growth cones guide axons in the developing nervous system Part 2 u 15 C Fawn Tyrosinated Acetylated merge microtubules microtubules NEUROSCIENCE Fourth Edition Figum 231 Part 2 Mm4quotMI yawn rum 221 Basic structure ofthe growth cone Part 3 Figure 232 The structure and action ofgrowth cones Part 3 Lamullpodia 285 D Filopodia Leading High 0 ms 125 ms ED ms edge A A A Factin 7 7 y assembly Law movement Fac n dcpulymcrizatinn NEUROSCIENCE Founh Edln39on Figum 232 Part 3 L 1 e wwwlvmulnawr1nuvmn 222 Major classes of axon guidance molecules Part 1 222 Major classes of axon guidance molecules Part 2 A Extracellular matrix molecules B Cll15 C Cadhurins D Nclrinslit family Cadherins Tyrosine KinaseslDther NCAM Kinam gtliex l signaling signaling quot molecules iimleq uleg v l lntegrin 1 r rs u cahanm recqators Furthersignal 39 Actin transduction lemwmn mnumn anmmmmrwmmm l t 22 Nlalm classes of axon guidance molecules VFquot 339th Lone interactions mm the enwmmnenl F an 2 E Semaphorins WMWMImwnannwwuu me Wmmnemuwn a n MCDB 47775777 Mo ecu ar Neurobwo ogy Lecture 21 Sensory mechamsme hearmg eh Hgawmm MW oumcax vecEmwe eM pmpemes Pmcessmu m m evem ca Egunes mvwsua mmvmauun Audnurv anamrw Huwme cucmea cumens messt MVES mm emuquot pu erma s 02mm aummw pvucessmu Lucauzauun m suund w M mmepmn m we mlhpcnmcnuls up T Smrulus 5mm mmm y sine w m mum Prmxxd on mm mm mwwmu k d anmm mm mm 7 1n Figure 1210 Organization ofprimary visual striate cortex Figure 1211 The basis offunctional maps in primary visual cortex Part ll Vertical electrode penetration Orientation tuning curves Receptive eld posiunn Spike rale E g 7 V a a 5 3 16511an innmmlm Oulpuh Annual131ml a 1 mlmmim mmgqpnnhluei 2 8 2 1 5 x 3 39 C B E 3 i i i 4 l c 339 Distance along elect ac NEUROSCIENCE roam Edition Flynn 1210 mm K Memoscuavca Fourth Edition Flgun 1211 Pan 1 kDislance along electrode trackX gun u Figure 1 11 The basis offun nal maps in p ary visual cortex Part 2 1 13 Columnar ga focular dominanc B Oblique electrode penetration A belt Right B Ocular dominance FWPS 3 Cortical cell Receptive Orientation eld position tuning curves x i i 71 i 7 r x1 39 E e i E g a 3 7 i 1 K Distance along electrode track gt1 Distance along electrode track NEUROSCIENCE Fourth Edition Figur 1211 Part 2 mwuux Wnuzamuucmmh 1111 Binocular disparities are generally th ght to be the basis of stereopsis Fixation paint lmngcs of fixation puinl Near disparities WWWambitan 1114 Magno and parvocellular streams Part 1 A P ganglion M gangliun cell cell Box B Random Dot Stereograms and Related Amusements Part 1 Binocular fusion pmducus sonsal mn that the shifted square 1 in hunt uf llw background plane 1114 Magno and parvocellular streams Part 2 B oniocellular yers K la Pa rvo cellular layers Magno cellular layers mmmmuw u my m MM 1117 The visual areas beyond the striate cortex are broadly organized into two pathways Figure 1217 Localization ofmultiple visual areas in the human brain using fMRl Parietal Dorsal Spatial analysis lobe pathway motion positional relationships m lenul in mm 11 Temporal Ventral Object recognition Iobe Pathway Shape color texture quotWMM rmng n u u an 5 me NEUROSCIENCE Fourth Edlh39nn Figu39o 1217 VVK vnnkAsl t 121 Periodic condensation and rarefaction ofair molecules produced by a tuning fork 122 A sine wave and its projection as circular motion TIfjniEg Concex c N 5 t S l t 3 t2 t 1 Sinusoidal wave Air pressure Normal atmospheric pressure 7 Distance gt ulmmlMunmlmnunru2 1mm Mm w 123 The human ear Part 1 123 The human ear Part 2 Semicircular canals Concha Vestibular nerve Cochlear nerve Eustachian tube Base of stapes in oval window membrane Pinna Tympan quotc membrane External a uditory meatus Whamman va m MW Kmu mumwm m mu 124 The cochlea viewed faceon and in cross section lPart 1 124 The cochlea viewed faceon and in cross section Part 2 Cross section of cochlea COChIea Vestibular 1 er 8 media mem ran Auditory A udi my nerve ipani Inner W hair cells flcr Basilar hair cells membrane Win Me r u inn 1 m mum n mmumlathu mm H m hm r 124 The cochlea iewed faceon andi oss sectio Part 3 125 Traveling waves along the cochlea Part 1 thlm 1 all g wummm 5 v ufinner Smpalun 2 hair cells quot quotquot quotquotquot 7 7 1 Km c i wimlw mudn 5quot mm Afl39k W lympan mmmnr 1mg Basilar B asHar r 1 haircells Tunnel Efferent embrane b d Afferent Basilar ofCorti axons narrowerys ffer mem ran W39 erv axons membrane more eXIbIe shapes mm Basilar membrane properties lead to tonotopy topographic mapping of different frequencies to different positions along length of cochlea mmmmmm own m a 126 Movement ofthe basilar membrane bends the stereocilia ofthe hair cells Part 1 126 Movement ofthe basilar membrane bends the stereocilia ofthe hair cells Part 2 A Resting position E Sound induced vibration Tectorial membrane Basilar lnmr hair cell membrane amtvulvqu wa a mmmrIpIIumlnn uu 126 Movement ofthe basilar membrane bends the stereocilia ofthe hair cells Part 3 127 The structure and function ofthe hair bundle in vestibular and cochlear hair cells D Q Shem39 torce Downward phase Wm mwuwu W umuw Mrs n u 128 Mechanoelectrical transduction mediated by hair cells 1210 The stereocilia ofthe hair cells protrude into the endolymph A Hypemola h n h B ligpoiaiizalion Tunnel of Cnrti n Spinl membrane ganglion 53 1 a vestibuli trin asrularis Bdsilar membrane MmmmlmlmrrwI7Inm 12 9 Mechanoelectrical transduction mediated by vestibular hair cells Par11r 129 Mechanoelectrrcal transduction mediated by vestibular hair cells Part 2 B A 15 25 E w E 10 IL a s 5 5 9 F E c k E 0 2 o q E a 90 2 ATime o 5 g 10 2 1 0 1 Hair bundle displacement um KmmmrwInwn x h u Wmmrmmimn may K 12 9 Mechanoelectrical transduction mediated by vestibular hair cells Part 3 1211 Response properties ofauditory nerve bers Part 3 Spikessecond d ct component 30 40 50 Time ms awn114503quot uth1 m on mmmmwpuru pur annual 1211 Response properties ofauditory nerve bers Part 1 1211 Response properties ofauditory nerve bers Part 2 A A20 B Frequency kHz 01 10 101 2 80 j 410 r E a a 15 7 4 0 2 13 quot8quot so 539 5 20 5 4m E 39E a a E 80 f f 7 2o quot 39 15 W Cochlea Basilar 3930 membrane 0 10 100 Cranial Frequency kHz nerve Vlll memuumuzxumru me yull lmarmmb n Box 0 Sensorineural Hearing Loss and Cochlear Implants Part 1 Box 0 Sensorineural Hearing Loss and Cochlear Implants Part 2 Microphone Implantable codrlear stimulator Headpiece Auditory WmmmuhWIizmmA n mmwo umcmmmm 212 Dlagram ofthe major auditory pathways 1 I Response properties ofauditory nerve bers Part 3 Cerebrum Primary auditory cortex Medial geniculate complcx of the Rostral midbrain thalamus Caudal midbrain C 39o 1 0 U m ll m a x quota at m iunclm Ponsmidbrain n MidPom Superior olive r Cochlear nuclei Rnstral medulla 39 nrsal p R l ostoroventral Antcruvontral MIWYInu a u u y 4 m u maummnwmu pun mt hum 213 How the M50 computes the location ofa sound by interaural time diff leading neuron Shorter path to neuron E Cochlea and cochlear nucleus lmmuurwlxu nun m MCDB 47775777 Molecular Neurobiology Lecture 11 Synapse mechanisms neurotransmitter receptors permeability and excitation vs inhibition Goals for today Understand what endplate currents look like Understand what reversal potential means Understand how permeability to different ions relates to reversal potential Understand how reversal potential relates to excitatory vs inhibitory conductances Understand spatial and temporal summation 514 Molecular mechanisms of neurotransmitter release Part 2 B 1 Vesicle docks 3 Entering Ca2 binds to synaptotagrnin quot 5 16 70 cc 993 60 o O Synaptobi evin Vesicle Syntaxin 5N A1125 2 SNARE Complexes form to pun 4 Ca2 bound synaptotagmin catalyzes membranes together membrane fusion 522 A neurotransmitter can affect a postsynaptic cell via two types of receptor proteins Part 1 A Ligand gated ion channels Ions Neurotransmitter 522 A neurotransmitter can affect a postsynaptic cell via two types of receptor proteins Part 2 B G protein coupled receptors N eurotr mitter G protein r aquot s 39 V IntraceW f w 515 Activation ofACh receptors at neuromuscular synapses Part 1 membrane patch ACh receptor Activation of ACh receptors at neuromuscular synapses Part 2 B Currents produced by Number of open channels Number 0 open channels yd manna ammqmaw Number Maul n 516 The in uence ofthe postsynaptic membrane potential on end plate currents Part 1 A Scheme for voltage clamping postsynaptic muscle fiber Axon of presynaptic motor neuron Voltage clamp amplifier Currentpassing electrode Postsynaptic I 3 muscle fiber quot39 Voltagemeasuring 7 electrode 516 The in uence ofthe postsynaptic membrane potential on end plate currents Part 2 B Effect of membrane voltage on postsynaptic end plate currents 4 4 6 0 2 4 6 Time ms 300 Time ms 518 Na and K movements during EPCs and EPPs Part 1 A NET ION FLUXES gt EPCs gt EPPs Postsynaptic membrane potential 100 mV EK B 90 mV 518 Na and K movements during EPCs and EPPs Part 2 c NET ION FLUXES gt EPCs gt EPPs mi A Only Kquot selective channel open 300 39 g 200 L 100 i O Q 7100 U Ea 200 W i a K influx 300 150 100 50 0 50 Membrane potential Na in ux EPC amplitude DA 0 150 100 50 O 50 Membrane potential NEUROSCIENCE Fourth Edition Figure 518 Only Na39l selective channel open 100 100 C EPC amplitude nA E EPC amplitude ILA The effect of ion channel selectivity on the reversal potential 300 200 100 0 7100 v 7 200 7300 C17 emuquot 7150 7100 750 0 50 Membrane potential 100 Cation nonselective channel open 150 100 50 0 50 Membrane potential 2005 Slnauer Assoolales Incl 520 Summation of postsynaptic potentials Part 1 A 31 2 r Excitatory E1 A Record Postsynaptic membrane potential Inhibitory I W 1 Excitatory E2 519 Reversal and threshold potentials determine postsynaptlc exaltation and inhibition Part 1 ENa 50 0 V m Threshold 40 50 Vrest 6O 70 Time ms 519 Reversal and threshold potentials determine postsynaptic excitation and inhibition Part 2 C D ENa 50 mV Threshold 4O Vrest 60 Time ms 520 Summation of postsynaptic potentials Part 1 A 31 2 r Excitatory E1 A Record Postsynaptic membrane potential Inhibitory I W 1 Excitatory E2 520 Summation of postsynaptic potentials Part 2 B Postsynap c membrane poten al mV Time ms gt MCDB 47775777 Molecular Neurobiology Lecture 1 Course Overview Neurons and Glia Cranial nerves Spinal nerves non bumdamrre NEUROSCIENCE Third Edilion Figun Lecture 0vm1ew 1 112 M InuudncLiDu m Lhecmlrse neurunsand g a Purvas at a1 P525 1713 2 114 W Extemal aumumy and basic subdi ms of me nerveus sysmmPImes et a ng 8157833 3 115 F Internal analomy ofmenexvoussystemlloodrbminbanier vaespgssssrm 4 121 W Resu39ng porentia ionic gmm39ems electrochemical equilime 1311111552131ng25759 5 123 F Vultagerdependam membrane pemleahiliry and acrimxpmemial Pm39ves er a1 Pgs 41760 6 125 M ActionparentialscomimxedJunchauualsandpumps Purves era Pgs 61783 7 123 W s 130 F 9 2 M Synapuc Lransmissiou Purves et a1 ngssim Werluesday Fm 4 2009 ham 1 Lectures 13 26 F 1 29 M Nelu ulmnsn nersandlheixrecepmrs Punes at a 1251197151 211 w 13 213 F Nemotransmmersand signal IIansduction Purves e1 a1 1251537176 14 ms M 15 ms W The Somatic Sensory System Fmes et 1 1352077228 16 220 F 17 223 M Pain Punes er 211 1251317st Werlnesday Feb 2009 Exam 21mms 916 111 227 F Visinurdevelupmeutjnammy ofiheeyaandphmuuansducdon Purvesel 31 1352537276 19 3 M Visuonrmfurmauonpmcessiug Pmesempgsmusa 20 31 W Vim mfmmauonpmcessingmm Purvas ml 135239310 21 56 F ThcAudiImy System Punes er a1 1253137342 2 39 M Th Ves1ibulaISystem Purves e a Pgs 3437362 13 311 W Che 39cal SensesrTaste and Smell Puwes er a1 Pgs3657393 24 313 F T11 Chemical Sensesr Small 2 315 M M0101 conu39ol Punes er a1 Pgs396421 Wednesday Mar 18 2009 Exam 3 Lenlures 1724 26 320 1 39 we wmhmm M P 1 3471 Spring Break NInr 307 Na Classes Relax and Refresh 27 330 M Ea y developmemufmenervoussys rem Puwes at al P55447565 8 41 w Generation cfnemalm39varsity dmmgdevelopmem PurvesetalPg 6757 28 4439 W Generation of neural diversity during development Purves at 31 123566574 29 443 F Axon outgrowth and pmhfinding Purvcs cl 3 P59577596 30 4M M Trophic factors in neural development Purvcs ct al Pg5596608 31 448 W Experienwdcpendcm modificau on of circuits Purves et a Pgs61 I 633 32 4410 F Synaptic plasticity Purvcs el 11 1135177203 3 443913 M 34 4 15 W Repair and Regencmtion in the NS Purvcs ct al Pgs635659 Fridny Apr 17 2008 Exam 4 Lectures 2533 35 420 M Cognition Purvcs el al Pgsb lb 36 443922 W Memory Purvcs cl 3 Pgs 791810 37 424 F Alzheimer39s disease Purves ct a Pgs 8 I 812 38 4127 M Parkimon s disease 39 4429 W Huntington s disease 40 51 F BSE and CJD Tuesday May 5 2009 730 10 pm Final Exam Cumulative 11309v 12 Examples ofthe variety of nerve cell morphologies found in humans Part 1 A Neurons in mesencephalic B Kenna nucleus of cranial nerve V bipolar cell C Retinal ganglion cell Dendrites Dondriles A Cell C b d Relinalamacrinn cell bodies 8 O Y rH Axon Axons Cell body E Cortical pyramidal cell o Dendrites Dendriles 15 Varieties of neuroglial cells Part 1 A Astrocyte B Oligodendrocyte body pI39OCESSES C Microglial cell 13 The major light and electron microscopical features of neurons Part 1 A N t ochondrion F39 n 13Panl 3 THEE 1mm gm gm Im m agrng gmmg fr Imammm g r r i 2 A C Synaptic endings r n Lawan 2 m m m am cam minis E Dendrites 39 F II 13Parl3 Mgr am 1113 mm s msg agni c reticulum 39 u 111 an Inn m gu m mam EF K3 963an 531 A G Myelinated axon and node 39 39 39 of Ranvier Mitochonch39ion 1139 n r 13Pan 5 we H it quoti i quot l izil b tubuhn tuban ac n 11 Estimates of numbers of genes in the humans mice ies and worms W 0 10000 20000 30000 40000 50000 Number of genes NEUROSCIENCE Third Edition Flgme 11 e 2004 Sinauer Associ es inc Cranial nerves Spinal nerves retinas 7 39 ganglia Dorsal root parasympathetic Sympathetic NEUROSCIENCE Third Edlliun Figun 1 1O Maior components ofthe nervous system and their functional relationships Part 2 B mass snozueu 9141193 MOTOR x CQWQNENIS k 7 7 V 5 SOMATIC 3 w MO OR a SYSTEM 3 quotI lt 2 U 5 1 3 Autonomic Ma th nerves 3 17 A simple re ex circuit the kneejerk response Part 1 Muscle sensory Sensory afferent axon Extensor muscle muscle Motor 2C lnterneuron axons efferent I A Sensory neuron synapses 39 and excites motor neuron in spinal cord V B sensory neumn 39aISO excites spinal intemei on C Interneuron synapse inhibits motor neuron to exor muscles rn I Pam


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