Psychobiology notes Exam 1
Psychobiology notes Exam 1 PSY 425
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This 29 page Study Guide was uploaded by Katherine Saed on Thursday February 5, 2015. The Study Guide belongs to PSY 425 at University of Miami taught by Dr. McCabe in Fall. Since its upload, it has received 218 views. For similar materials see Psychobiology in Psychlogy at University of Miami.
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Date Created: 02/05/15
82614 Psychobiology is a behavioral science goal is to understand behavior Neuroscience interdisciplinary eld to explain how brain works and how behavior comes about These 2 elds have merged 1 History of psychobiology 1800s scienti c investigation of brain and behavior began Localization of function speci c locations with certain functions Gall had the idea that functions in the brain could be segregated into individual regions 0 Phrenology Noticed bumps on outside of scalp and he hypothesized that the bumps were formed when a certain part of the brain was utilized Scienti c community didn t like the pseudoscience Flourens performed scienti c experiment with cats looking at portion of the brain the Gall said was the romantic section it was the cerebellum gt observed cats after removing this portion and they were still capable of producing babies 0 Determined something as speci c as romance cant have its own region in the brain Broca in 1860 this neurologist had patients with aphasia lack ofspeech o Waited until patient quotTaquot died and examined brain which had damage in inferior frontal lobe in the left hemisphere 0 Looking at other brains with damage on the right hemisphere these people had no language impairment Wernicke discovered region farther back in the left hemisphere that was related to comprehension of language Late 1800s methods of studying workings in brains o Galvany developed galvanomitor so you could amplify nerve cells to see what each was doing 0 Santiago Ramon y Cajal anatomist looked at dead tissue nerves and determined function by how they were connected Neuron Doctrine The neuron is the basic unit of the nervous system All brain activity and behavior can be explained by the activity and interaction of these nerve cells Darwin same time period he was studying evolution l led to scientists studying animal brains because they now realized they were related to humans Early 1900s Walter Cannon and Ivan Pavlov won nobel prizes for work in basic physiological processes 0 Both understood that physiology and behavior are closely linked and must study them together Lashley studied neuromechinisms of learning and memory eld is 8090yrs old 2 Methodology in Psychology A Paradigms Physiological intervention manipulate physiology and observe how this changes behavior invasive Behavioral intervention manipulate organism s behavior and observe changes in the physiology noninvasive often performed on humans AKA psychophysiology Correlational approach 2 dependent measures physiology and behavior and you correlate them see how they covary overtime l can t infer causality Paradigms are not very sophisticated B Techniques Stereotaxic surgery instrument xes organism s head in a particular orientation and it allows you to move an electrode in certain ways Measured exact coordinates of different portions of brain so you can know that the electrode is being moved to the right place good to manipulate parts of brain Ablation destroy tissue Scientists have lowered an electrode into the brain sending DC current which burnsdestroys tissue create lesions in brain Want to know what happens when a part is destroyed REALLY want to know how the brain compensates when that region is destroyed Possible destruction of neuron l may wrongly interpret what the portion of the brain does due to destroyed connection pathway Stimulation exciteactivate neurons l stimulate tissue current can spread though and you may be stimulating more than one region Recording can put electrodes into or on the brain and look at electro activity of a single nerve cell or as a group multipleunit recordings EEG can put electrodes on scalp and observed millions of nerve cells Intracellular recording insert pipet into a single nerve cell Biochemical techniques Microdialysis probe inject uid through a canula and put suction on the second cannula to suck up uid can perfuse tiny areas of the brain 0 Perform biochemical analyses on tiny quantities Nissl Stain ribosomes are what are really being stimulated in the cell this stain is really staining a cell body 0 Nucleus cluster of nerve cell bodies can identify brain nuclei Golgi Stain stain that lls entire nerve cell only taken up in 1 of neurons Intracellular stains can be used to insert into single cell Imaging Electron microscopy looks at cellular and molecular level activity Tracing techniques Anterograde tracers substances are transported down the length of the axon through microtubules determine where nerve cell projects to Retrograde tracer project tracer into axon terminal and tracer travels backwards to the cell body 0 With tracers a roadmap of the brain is created lmmunocytochemistry An antibody with a uorescent tracer show positions of molecules use different tracer for different molecules Brain Imaging BIG revolution 0 Angiogram inject die into blood circulation of brain and the die highlights vascular tree of brain see aneurisms and clots 0 CT Scan xray picture of brain through different levels 0 MRI imaging magnetic properties of magnetic regions in brain much clearer resolution than CT 0 Functional imaging Neuroscience wants to know activities in brain I Attach radioactive label to sugar that would be taken up by cell most active cells take up most radioactive labels because they take up most glucoseenergy 0 PET Scan give substances that are taken up by cells that have a radioactive label and PET imager looks for radioactivity in cells I Spacial and temporal resolution are not good person must engage in task for 2030min to get response 0 fMRI functional looking at blood ow and oxygen utilization most active areas of brain get most blood ow and take up most oxygen get special imaging of MRI and temporal imaging is great within seconds I Look at brain activity while people are engaged in tasks Tissue Culture cells in culture remove nerve cells and watch them grow and make connections In Vitro brain slices can take slices and keep them alive to study them for days in vitro Transgenic animals can alter genome of an organism mice are often used target speci c gene and knock it out of the genome and see what changes occur knockout animal OR insert a gene into genome and see in uence knockin animal 82814 Neuroscience deals with connections in the brain and pathwayssystems 1 General issues A Planes 1 Saggital sections slicing brain down midline and continue down one hemispher and turn sideways 1 hemisphere at a time Midsaggital slice right down the middle 2 Coronalfrontal sections slice through front portion and then cut backwards 3 Horizontal sections slice across the top and move down B Directions 1 Medial vs Lateral medial means towards the midline and lateral means away from the midline de ne medial vs lateral in terms of relationship to other parts of brain 2 Doral superior vs Ventral inferior Dorsal is top of brain amp back of body and ventral is bottom amp front of body 3 Anterior rostra towards nose front of skull vs Posterior caudal towards tail bottom of skull anterior is front and posterior is in back ln Spinal cord posterior and dorsal meet up and anterior and ventral meet up C Organization of Nervous System Nervous system aCNS b PNS l a somatic nervous system b Autonomic I a Parasympathetic b Sympathetic 2 Peripheral Nervous system A Somatic nervous system skin joints muscles provides sensory information from your bodyface ie touch pain temperature and provide motor commands to muscles of your body Peripheral nervous system made up of nerves that come off of ours spinal cord from your neck all the way to the lower back nerves come out of cord in pairs 31 pairs in total each nerve innervates a particular region of skin and muscle l Dermatome the portion of skin innervated by single nerve Myotome area of muscle innervated by single nerve Ex One nerve out of the spinal cord at base of neck is a cervical segment 8th the nerve projects to a speci c region outer portion of hand Grey matter is made up of nerve cell bodies unmyilenated axons and dendrites White matter is made up of myelinated axons Sensory information system is sensed by sensory neurons these neurons project though spinal nerve branches one branch goes to the dorsal part of curve and one goes to ventral part sensory information travels through the dorsal route of the spinal nerve completely sensory if damaged you lose sensation but not motor control buge in dorsal Dorsal root ganglion cluster of nerve cell bodies found out in the body nucleus ganglion Travel from ganglion to the dorsal horn receives sensory information from the body From dorsal horn neuron can dive right into white matter and go straight to brain or synapse right by the dorsal horn between sensory and motor neurons interneurons and from there go into the grey matter aka Ventral horn within ventral horn are cell bodies of motor neurons Ventral horn sends neurons through ventral root and axons join up with common spinal nerve and travel out to muscle of the body Re ex arc sensory motor loops controlling activities in the body Ex Knee jerk re ex All about SENSORY MOTOR INTEGRATION B Autonomic Nervous system visceral organs guts Considered an output system only only efferents Efferents Neurons that project away from the body Afferents ie Sensory neurons start out in body and project into the central nervous system Made up of 2 neuron chains 1St neuron preganlionic cell myelinated originates in spinal cord or brain system and projects into the body where there are ganglia and the rst neuron synapses with the second neuron postganglionic cell unmyelinated within the ganglion and the second projects from the ganglion to a target organ 1 Sympathetic system ght or ight activates parts of your body in emergency situations heart speeds up more forceful breath faster pupils dilate adrenaline is released innervates salivary glands and trachea intestines shut down constrictdilate blood vessels Originates in the spinal cord Thoracic and lumbar segments portions of spinal cord from base of neck to lower back IML intermediolateral nucleus long skinny nucleus within thoracic and lumbar segments containing preganglionic neurons of the central nervous system 1 neuron from IML to ganglion and 2nOI is from ganglion to target organ Paravertebral chain sympathetic chain lies right next to the vertebrae on either side of spinal cord where the sympathetic preganglionic neurons synapse and then go to target organ Adrenal gland receives direct projection adrenaline is release so body works overtime Time for system to kick in initially is fast from spine to ganglionmylenated neurons but the chain to the target organs can be long because the neurons are UNmyelanated which makes the conduction slow Adrenergic system what Sympathetic system is considered Acetyl Choline ACH Neurotransmitter between pre and post ganglionic neurons Norepinephrine NE or noradrenaline Drugs exist to target these synapses affect adrenaline levels 2 Parasympathetic system originates in CNS in the cranial brain stem and sacral originate in tail part of spinal cord regions System slows down Vagus nerve most important parasympathetic system aka 10th cranial nerve this nerve exits from brain stem and goes into the body and branches l innervates just about every organ in your body On or near the target organ there is a ganglion and the pre and post ganglions then innervate the organ Considered to be faster because long stretch with myelinated axons and short portion with unmyelinated axons Cholinergic system neurotransmitter at the ganglion is acetyl choline ACH ACH is also found in between synapses Ex Atropine put in eyes to dilate pupils by blocking action of ACH in the iris l drugs can affect the parasympathetic system as well 3 Spinal Cord lowest level of the CNS about 12 in big lncased within vertebrae which is made up of 31 separate bones in between vertebrae are spongey disks allowing spinal cord to move twist bend Grey matter is surrounded by white matter spinal nerve comes off Spinal nerves exit between dorsal and ventral parts of vertebrae l pinching spinal nerve can cause body pain if you pinch dorsal l sensory problems ventral root l motor problems Meninges membranes l in amed meninges leads to meningitis compromise brain and spinal cord Dura Mater Cerebral spinal uid baths the spinal cord Spinal cord ends somewhere in the middle of the back even though vertebrae reach lower back nerves on spinal cord may be higher up than its paired vertebrae nerves 31 segments of spinal cord 8 are cervical segments top of cord 12 thoracic segments 5 lumbar segments middle to lower back 5 sacral segments bottom of back 1 coccygeal segment near tailbone Easy for cord to become compromised traumatic injury can lead to paralysis Thoracic cord and below no sensory and movement in lower limbs Cervical segments control your upper limbs more grey matter Lumbar control the lower limbs more grey matter Ascending tracks send tracks into brain Descending tracks from brain into spinal cord Nervous system is organized anatomically according to the function 9214 4 Brain about 100 billion cells in the brain Job of the brain is to bring in sensory information and integrate it then produce motor out ow behavior l sensory motor integration Organized hierarchically primitive parts are shared with other animals re exive actions and over years successive layers of tissues developed over the other lower parts of the brain these higher brain regions take control through inhibition A Myelencephalon lowest part of the brain cephalon in the head 1 Medulla extension of the cord gets a little larger Vegetative functions functions designed to keep organism alive ie breathing heart rate blood pressure swallowing Damage to medulla is generally fata Major pathways with sensory information and cables taking motor information from brain into the cord throughout the medulla Reticular Formation a bunch of nuclei and bers that form a web of neurons that run through the medulla through brain stem to diencephalon l RF Sleep dreaming arousal attention Medulla nerve to know X tenth cranial nerve the vagus nerve B Metencephalon 1 Pons quotbulbar regionquot adjacent to the medulla Primary functions are vegetation sleep dreaming breathing Ascendingdescending motor tracks to and from spinal cord V nerve acousticvestibular nerve sound and balance sensory nerve that comes from the inner ear V nerve Facial nerve a motor nerve that controls the muscles of the face projects from pons to the facial muscles V cranial nerve largest cranial nerve trigeminal nerve provides sensory information from your face tingles pimple pain tooth aches Has motor bers that go from neurons to the jaw l controls muscles of mastication aka chewing Face is heavily innervated and it is so sensitive because of this V cranial nerve 2 Cerebellum main function is motor control balance posture motor guidance providing predictions and timing to make motions uidcontinuous and accurate Critical for motor learning Same wiring in human brain as it is in any other animal Myelencephalon and Metencephalon are referred to as the quothind brainquot C Mesencephalon 1 quotMidbrainquot has ascendingdescending tracks tofrom spinal cord Contains sensory relay nuclei l sensory information comes into the brain and synapses in these structures before it gets sent elsewhere Superior colliculus sensory realy nucleus for vision lnferior Colliculus sensory relay nucleus for hearing known together as the tectum Motor nuclei Red nucleus cell bodies project down into brain stem and spinal cord and are involved with controlling muscles of our limbs Substantia nigra if you cut through the brain these cells look black neurons project upward through the telencephalon towards the basal ganglia contain neurotransmitter dopamine these neurons diedeteriorate in Parkinson s lll Nerve oculomotor nerve controls eye movements D Diencephalon 1 Thalamus the gatekeeper to the cerebral cortex lies along midline of the brain important structure a Many sensory relay nuclei major sensory way station in the brain many terminate in the thalamus Lateral geniculate sensory relay nucleus for vision gets input from the eye and synapses there and sends information up to the cortex Medial geniculate sensory relay nucleus for audition information from inner ear makes its way here and information gets sent to temporal lobe to the auditory region of the cortex Ventral posterior lateral nucleus VPL sensory relay nucleus for somatosensory pain touch temperature sense with skinmuscle signal from spinal cord to here all sensations from neck amp below go here Ventral posterior medial nucleus VPM gets all input from face and head regions the trigeminal nerve sends the information to the VPM which then relays it to the somatosensory cortex b Intrinsic nuclei don t project to speci c part of cortex but project to the cortex and fan out to make contact with millions of cells l receive their input from the reticular formation and the intrinsic nuclei send info to cortex Brain s arousal system needs to be aroused to process information ef ciently ie problem solving 2 Hypothalamus lies beneath the thalamus hence hypo small structure that sits right through roof of the mouth Made up of subnuclei a Motivated behaviors Involved in a cluster of activity known as motivated behaviors regulation of eatingdrinking temperature regulation sexual behavior and reproduction certain emotional behaviors like aggression rage and violence Has nuclei that control the autonomic nervous system b Hormonal function pituitary gland Controls the pituitary gland Ideal location to control body Controls hormonal secretions controls ANS organs in the body involved in simple emotional behaviors and regulates important processes that keep us alive l does so through interaction Myelencephalon Metencephalon Mesencephalon and diencephalon are known together as the brain stem E Telencephalon 1 Limbic system a Hippocampus seahorsequot amygdala almondquot fornix septal nuclei hypothalamus thalamus olfactory system b Regulates emotion heavily involved in learning amp memory 2 Basil Ganglia clusters of nerve cells found in the brain a Caudate nucleus putamen globus pallidus Caudate and patemen referred to as striatum Pallidus is referred to as the pallidum b Important in motor control damage to the 86 get a whole series of motor dysfunctions postural problems dif cult initiating movements develop tremors Controls through interaction with the cerebral cortex Diencephalon and telencephalon are known together as the forebrain 3 Cerebral cortex large sheet of tissue that is stuffed into the cortex Cerebral groove sulcus a long deep groove ssure Ridgeraised portion gyrus a Paleocortex more primitive cortex with 4 or 5 cell layers Af liated with limbic system b Neocortex vast majority of the cortex that has 6 cell layers c Regionslobes Occipital lobecortex primary feature is the visual cortex one of the highest levels of the visual system Parietal lobe above occipital lobe primary feature is the somatosensory cortex l Posterior parietal lobe involved with coding for space where things are in space auditorially visually Temporal lobe major features are the auditory cortex and parts of the olfactory cortex smell on the medial surface is a part of the cortex that is very important in certain types of memory Frontal lobe primary function is the primary movements and in higher order executive functions F Major Pathways 1 Corticospinal tract aka pyramidal initiates in cerebral cortex and ends in spinal cord Neurons send axons down and bundles descend to the medullalower brain stem and about 95 cross over to other side of brain crossing is known as pyramidal decussation Neurons will leave the tract at some point in the cord and synapse with motor neurons in that region G Commissures sideways connections between two hemispheres 1 Corpus callosum H Ventricles 1 Lateral ventricles connected to the III third ventricle and then to the IV ventricle Cerebrospinal uid found between these ventricles cushions the brain and helps carry chemicals throughout brain I Blood Supply 1 Two carotid arteries and two vertebral arteries 2 Circle of Willis all 4 arteries feed into this network of arteries at the base of the brain helps protect brain from things like clots 3 Blood brain barrier cells that line blood vessels of the brain and help to screen out certain types of molecules 9414 Neurochemistry Our actions are the result of activity of nerve cells 1 Neurons A Soma nerve cells all have cell bodies aka Soma or Perikaryon Cell body has all the machinery keeping the cell alive mitochondria energy organelles waste DNA reproduction B Dendrite receptive portion of the neuron that receives information from other cells single nerve cell can have many dendr es 0 At the tip of the dendrites is swelling that is a dendritic spine where synapses happen C Axon transmissive portion of the nerve cell away from soma and towards the next cell usually only 1 axon per cell 0 Axon hiock conical shape protrusion from the axon spike initiation zone 0 Axon can branch into collaterals split and synapse with other cells 0 Axon is a hallow tube in which there are smaller tubules microtubules capable of transporting chemicals to and from soma o Axonal transport is the transport through the microtubules o Boutons little swellings at the tip of axon axon terminals synapse with the next cell s dendritic spines Can classify nerve cells by number of branches that come off the soma o Monopolar one branch lots in invertebrates humans have some 0 Bipolar one dendrite and one axon 2 branches 0 Multipolar cells many dendrites and a single axon most common Most common categorization is through the diameter of the soma o Mammals tiny nerve cells 10 microns 10quot6 meter I Large neurons 5075 microns o Invertebrates giant nerve cells 300 microns can see with eye Neuropil dendrites and axons other cells in open space between nerve cells Extracellular matrix protein scaffold between the nerve cells that help provide structure Cells all oat around in uid quotsoupquot 3 Glia glial cells are nonmoronal cells Produce molecules and aid neurons in the course of development as well as in the adult brain A Astrocytes activated in response to injury in the brain may have role in healing process mostly found on or near bordersboundaries in the brain such as lining ventricles and on blood vessels may play critical role in blood brain barrier Help form a barrier that isolates brain from rest of body B Microglia tiny glial cells that are produced and then migrate to site of injury in the brain aka phagocytes Phagocytosis engulf debris and take it away Glial cells can multiply rapidly for this reasons brain tumors are often made of glial cells that multiple out of control C Oligodendrocyte often called satellite cells nd them near nerve cells 1 Myelin sheath myelinate axons by wrapping membrane lipid layer around the axon creates fatty later around the axon 2 Nodes of Ranvier segments of bare axons in between the oligodendrocytes that are wrapped around insulation prevents electrical impulse so it looks for the next point of low resistance which would be these segments so the impulse jumps from node to node 3 Saltatory conduction leaping of the conduction by the electrical impulse much faster than the process in an unmyilenated axon D Schwann cells also wrap around nerves and body and myelinate them 4 Electrical Activity of Nerve Cells Neurons are electrically excitable tissues receive produce and transmit electricity A Potentials electricity is characterized by movement of charged particles greater the difference in charges between particles the greater the potential for movement inside of cell relative to outside of cell inside is about 70 mV more negative Potential voltage B lons Sodium cation potassium cation Chloride anion molecules that carry charge and are responsible for activity in the nerve cells C Cell membrane barrier between inside and outside of the cell lon channels huge proteins throughout the membrane that allow ions to move in or out permeability IF permeable they try to move toward equilibrium and cell becomes depolarized LESS polar D Resting potential inside of the cell is negatively charged compared to the outside of the cell 70 millivolts of a volt resting potential measuring potential always refer to inside of cell relative to outside of the cell State of cell when nothing is happening Cell is polarized in this state E Depolarization if cell membrane becomes permeable than ions can move and the cell would be depolarized Depolarization is exciting the cell squid has giant axon great for studying electrical properties of nerve cells F Electrical and chemical gradients Potassium high concentrations inside cell and low outside the cell chemical gradient pushes it to move out of cell Sodium high concentration outside cell and low inside chemical gradient pushes it to move out of cell Chloride found in high concentrations outside cell low inside cell chemical gradient pushes it to move into the cell These ions that have a tendency to even out their concentration create the chemical gradient When cell is at rest the potassium and chloride channels are open and ions are free to move but they don t move when cell is at rest due to electrical gradient Potassium and chloride are more or less at equilibrium because of the electrical gradients and the distribution of charge Sodium wants to move inside positive ion and wants to move to negative so this and the electrical gradient WANTS it to get into cell BUT at rest sodium channels are closed G NaK pump forces any sodium that sneaks in when cell is at rest out of the cell 5 Action Potential occurs because cell loses its ability to keep sodium out of the cell Something drives cell to reach 50millivolts and the Na channels will ing open because they are voltage dependent Na ions pour into cell when channel opens and drive membrane potential straight up to about 50millivolts this is the action potential ALL action potentials are the same size all go to Na equillibrium A Na ions at 50millivolts Na is at equilibrium B All or none action potential is all or none because when ood gates open the Na will all come owing in and when you hit critical potential you get the full action potential if you don t hit threshold you get no action potential C Na equilibrium at 50millivolts where action potential is reached 6 Stages of recovery NaK pump Potassium ef ux Potassium is no longer happy so it starts to leave the cell inside goes more negative so membrane potential starts to fall A Absolute refractory period no way cell can re again because potassium is leaving and ions are in such terrible positions it is just not possible 1 millisecond period this period determines speed at which nerve cell can re fastest are a few hundred times a second B Relative refractory period molecular pump pumps sodium out of cell and exchanges it for potassium 1Na per 2K pumps out more ions so membrane potential continues to fall a Enough ions on positive and negative sides that it is possible for cell to re re C Supernormal period brief instant the cell is hyperexcitable because it is right at the threshold where an action potential is triggered D Subnormal period pump drives membrane potential below resting potential E Resting potential cell is now ready to re again 7 Neural Conduction A Cable properties nerve cells are like cables and when electricity is generated at a point the current will travel to next portion of membrane driving it to threshold and sodium comes in and action potential occurs this ripples down the whole membrane Action potential is conducted at a xed altitude because a full potential is conducted at each point B Unidirectional conduction only travels one direction because of refractory period membrane behind the action potential is refractory so the potential can t travel backwards only forwards Only different where the 1St action potential is produced it can go in both directions This is for unmyelinated axons For myelinated axons cell membrane is insulated which doesn t allow a potential to be generated so it instead jumps to the nodes which is the next chunk of tissue that it can spread current to I only produces action potentials at nodes Faster in myelinated axons 8 Graded potentials A Dendrites and somas where graded potentials occur B Graded strength varies smaller the stimulus smaller the potential C Decremental as the signal travels away from membrane it gets smaller Different from action potential which is all or nothing at a xed altitude vs the graded potentials that vary in size and decrease in strength Action potentials occur in axons vs graded potentials on dendritessoma Axon hillock where the graded potentials turn into action potentials spike initiation zone lf depolarization is great enough hit the threshold and action potential occurs It is unlikely that a single graded potential will produce an action potential D Integration of information cell membrane integrates information from different cells 1 Summation multiple graded potentials can summate and a larger graded potential will be produced possibly large enough to cause action potential 2 Spatial summation more than one graded potential arrive at the axon hillock together and they summate into larger graded potential 3 Temporal summation a graded potential reaches hillock right after another and they will build up with the previous graded potentials E Excitatory postsynaptic potentials EPSP pluses Depolarization drives potential towards threshold F Inhibitory postsynaptic potentials IPSP minuses Hyperpolarizaton Some graded potentials can actually drive the membrane potential away from the threshold l inhibition Hillock monitors how much excitatory and inhibitory polarization is made l if pluses outweigh minuses at any moment the axon hillock will re 9914 Neurochemistry Chemical synapses rather than electrical synapses hardwired easier to regulate more types of actions malleable changeadapt Elasticity 1 Synaptic transmission A Synapse connection between 2 nerve cells B Presynaptic cell 1St step in transmission synthesizes neurotransmitter chemical and it gets transported through the axon in microtubules stores in vesicles in the axon terminal C Postsynaptic ce across synaptic cleft from the presynaptic ce Synaptic cleft small space between presynaptic and postsynaptic cells D Synaptic mechanisms 1 Transmitter synthesized in presynaptic cell and it gets transported through the axon in microtubules stores in vesicles in the axon terminal 2 Transmitter stores in vesicles vesicles protect neurotransmitter from being degraded by the enzymes neurotransmitter is sitting in axon terminal of presynaptic cell Presynaptic cell res potential 3 Ca in ux vesicle movement Need this for synaptic transmission Action potential opens calcium channels Vesicles fuse with cell membrane and neurotransmitter moves out into the synaptic cleft 4 Transmitter diffuses across cleft millisecond delay during diffusion l time limiting step in transmission a Autoreceptorsfeedback mechanism transmitters bind to these feedback system for the presynaptic cell to tell it how much transmitter has been released Neurotransmitters move to receptors on the postsynaptic cells whichever transmitters diffuse in the direction of the cell others had diffused to receptors on presynaptic cell 5 Transmitterreceptor binding neurotransmitters bind on postsynaptic cell s receptors a Transmittergated ion channels 1St type of receptor if neurotransmitter binds can open channel ie sodium channel when opened cell is depolarized l EPSP VERY fast transmission through gated channeb b EPSPs and lPSPs depends on type of channel EPSP If gated ion channel was a sodium channel when opened cell is depolarized IPSP If it was a chloride channel negative ion inhibition IPSP Potassium channel opened l hyperpolarizes cell c Gproteincoupled receptors 2nOI type of receptor neurotransmitter binds to a receptor molecule which then activates a chemical inside the cell known as a Gprotein Activated Gprotein can open up an ion channel or more often it can activate an enzyme inside the cell 2nOI messenger system Enzymes trigger chemical reactions Cheml l chem2 changes biochemistry of the cell Ex Cyclic AMP Metabotropic effect affects metabolism of the cell the system of gprotein activating enzyme causing chemical changes Receptor population is always changing l can have more or less and be more or less excitable depending on how much stimulation is occurring 6 Transmitter breaks off receptor drifts back into synaptic cleft 7 Transmitter inactivation a Diffusion away neurotransmitters diffuse away into space b Enzyme degradation enzymes are sitting in the cleft and they can cleave the transmitter or inactivate it by changing structure essentially they will just inactivate the neurotransmitter c Reuptake by presynaptic cell protein molecules called transporters sit in the cleft and they take the transmitter from it and transport it back to presynaptic cell here portion of membrane breaks into vesicle and gets pulled back into cell l recycling transmitter 2 Characteristics of receptors determine the response A single neurotransmitter can have multiple reactions excitatory or inhibitory Depends on characteristics of receptors not the neurotransmitter 3 One neurotransmitter per neuron lDale s lawl Neurons also release peptides amino acid chain and are often co released with neurotransmitters Peptides still change the way the neurotransmitters work but not a true neurotransmitter 4 Drugs most work at the level of the synapse Exogenous substance and produces effect somewhere in body Does it cross blood brain barrier Huge determinant in its effect A Agonists drug that acts to enhance or mimic the action of a neurotransmitter 1 Drug can get into synapse and facilitate more release of transmitter 2 Drug can bind to the receptor and activate it only happens if drug has a similar structure to the neurotransmitter 3 Inhibit reuptake of the neurotransmitter 4 Inhibit the enzyme that metabolizes the neurotransmitter so more neurotransmitter is left in the synapse enzyme wont destroy B Antagonist oppose or block the action of a neurotransmitter 1 Drug blocks release of neurotransmitter 2 Binds to the receptor and blocks it 3 Interferes with the synthesis or storage of neurotransmitter 5 Neurotransmitters communication in the nervous system Point to point communication localdiscrete communication between neurotransmitters ie movement Broadcast communication sent through bloodstream Diffuse modulatory system Neurons also have broadcast communication through the branches synapsing with hundredsthousands of cells ie emotion arousal learning Most neurotransmitters are either amino acids derived from amino acids or are peptides of amino acids a Amino acid transmitters 1 and 2 GABA Glycine work mainly through pointto point communication mediate between discrete localized cells Open up channels that allow ions to move in Fast transmission and discrete localized information transfer Inhibitory neurotransmitters because of hyperpolarization due to binding to the ion channels allowing ions inout Has to do with the receptors these transmitters bind to Higher brain regions often inhibit lower brain regions Types of drugs that act on these transmitters Barbituates used as anesthetics they bind to receptors and enhance GABA Benzodiazepines zanax or valium reducing anxiety drugs GABA agonists enhance the activity of GABA Valproic acid depakote can treat epilepsy reduces excitability of the brain 3 Glutamate works through transmitter gated ion channels and pointtopoint communication The major excitatory transmitter in the brain unlike GABA and Glycine that are inhibitory because it depolarizes the cell to make it excitable Glutamate toxicity when brain is injured these cells release glutamate in large quantities and it becomes toxic because it kills neurons Brain overproduces cells and synapses so this is a pruning mechanism that kills cells in a natural way but during injury it isn t good NMDA activity dependent receptors glutamate binds to them the NMDA channel is blocked by a Mg ion When it reaches a critical level of depolarization the Mg gets kicked out and then sodium and calcium can enter Activity dependent because its only functional when the cell is suf ciently activated more cell is used the more activated it becomes nonNMDA receptors when activated Na moves into cell Normally at rest glutamate is released and binds to both receptors and nonNMDA opens and cell is depolarized by sodium Once cell is suf ciently polarized by nonNMDA channels the Mg gets kicked out and this is a mechanism to get calcium in which triggers biochemical pathways B Acetylcholine derived from molecule in your diet called choline neurotransmitter at the neuromuscular junction Important transmitter in the brain can regulate activity of the thalamus send neurons into limbic system and hippocampus learningmemory cells in nucleus basalis and these neurons project up into cortex all diffuse modulatory projections branch into millions of cells in these systems These are the rst cells that begin to die in alzheimer s disease Some work in pointtopoint communication and some in diffuse modulatory system in the brain Diffuse modulatory system work through Gprotein coupled receptors Multiple receptors Nicotinic receptors nicotine transmitter gated ion channeb In between muscles of body Muscularinic receptors muscarine Gcoupled protein receptors Found in autonomic nervous system and in the brain Acetylcholine esterase ECHE enzyme metabolizesbreaks down acetylcholine Drugs working on these synapses Curare comes from plant gets into acetylcholine synapses and binds to their receptors and blocks them antagonist cause temporary paralysis because intermuscular synapses are blocked many snake venoms work in the same way Botulinum toxin gets into synapses and blocks release of acetylcholine antagonist can be used as botox by paralyzing muscle a lot of nerve gases work on acetylcholine synapses Black widow venom causes continuous release of acetylcholine agonist causes synapses to re out of control leading to spasms and eventually you run out of acetylcholine and you can run out of air Many insecticides inhibit the acetylcholine esterase agonists in doing so it kills the insect blocks destruction of acetylcholine C Bioamines monoamines amino acids are converted into these transmitters 1 Catecholamines all derived from tyrosine amino acid know substances and the enzymes they come from on slide in ppt Pathway Dopa by dopadecarboxylase l dopamine l noradrenaline l adrenaline A Dopamine found in the brain in discrete pathways cell bodies originate in the brainstem two important clusters 1 Nigralstriatal bundle substancianigra whose neurons project up to basal ganglia where they form this bundle neurons important for motor control malfunction and cause akinesia dif culty moving postural rigidity hold posture forever and tremors 2 Ventral tegmental area project neurons to limbic system mesolimbic system and another goes from ventral tegmental to the frontal lobe mesocortical system All these neurons are diffuse modulatory neurons and work through Gprotein coupled receptors Multiple dopamine receptors known as D1 D2 D6 Two enzymes metabolize dopamine monoamine oxidase MAO and COMT Many drugs working on dopamine synapses 1 Amphetamine stimulates release of dopamine agonist and it inhibits the reuptake of dopamine agonist leaves more in cleft 2 Pargyline MAO inhibitor angonist inhibiting the enzyme that metabolizes dopamine 3 Chlorpromazine thorazine given to acutely psychotic patients it terminated the hallucinations and delusions rst in the class of drugs known as neuroleptics Haldol acts like chlorpromazine these drugs bind to and block dopamine receptors mainly D2 Developed sideeffects known as tardive dyskinesias because drug also blocked synapses in the nigralstriatal bundle 4 Cocaine inhibits reuptake of dopamine agonist strong stimulant because it stimulates the mesocortical and mesolimbic systems which work in reinforcing behaviors that are adavae Appetitive motivational system how the mesocortical and mesolimbic systems are referred to brain s pleasure pathway James Olds lowered electrode into brain of rats and allowed animal to press a bar that activates stimulating electrode the animal pressed it 10000 times in a row discovered the pleasure sensor animal would rather stimulate brain than do anything else Designer drugs restructure addictive drugs so they wouldn t be illegal many younger people started showing up to hospitals with Parkinsons systems all took a drug made by a chemist called MPTP highly toxic substance that kills neurons in brain MPTP shares similarities to herbicides and pesticides B Norepinephrine adrenergic synapses Locus coeruleus major cluster found in the pons send neurons through brain through diffuse modulatory system Make neurons more responsive to enhance information processing Metabolized by MAO and COMT like dopamine is Alpha and Beta receptors Drugs Amphetamine makes brain more active and alert Adderall works on attention MAO inhibitors like Pargyline will also increase amount of norepinephrine Tricyclics Elavi tofranil inhibit reuptake of norepinephrine and of serotonin agonist and it improves mood C Epinephrine adrenaline norepinephrine converts to this is cell is there not playing a big role as a neurotransmitter Produced by adrenal gland and circulates body as adrenaline 2 lndoleamines A Serotonin derived from amino acid tryptophan comes from diet Tryptophan l 5HTP l 5HT serotonin MAO inhibitors are nonspeci c cause side effects work on serotonergic systems Serotonin is metabolized by HIOMT an enzyme Diffuse modulatory system neurons that project into brain and make connections with thousands of other cells modulate all these at once Studied intensively in terms of sleepdreaming RAPHE nuclei cluster of nuclei along brain stem Constrains activity in circuits that deal with impulsivity aggression hostility Trycyclics prevent reuptake of norepinephrine and serotonin may have something to do with mood disorders tricyclics used to treat depression 1960s LSD worked on serotonin receptors produce hallucinations and psychosistype symptoms Binds to autoreceptors and stimulates them which then automatically shuts down receptors 1985 Prozac rst of SSRls selective serotonin reuptake inhibitor since then paxil zoloft celexa have been created l agonists because it leaves more serotonin in the synapse Drugs work because these people have low serotonergic control and SSRls can treat these depressive symptoms When SSRls were rst distributed many committed suicide many became manic D Retrograde messengers sends a message from postsynaptic cell to the presynaptic terminal tells when it has been polarized depolarized NO nitric oxide a gaseous molecule cell in brain produces this it diffuses through the membrane of postsynaptic cell to that of the presynaptic cell sending a message to produce more neurotransmitter molecule metabolized fast CO carbon monoxide can get in easily and it can be fatal E Neuropeptidesneuromodulators the peptides work on synapses but don t work as true neurotransmitters neuropeptides are released into synapses and affect how they work hundreds in the brain Endorphins endogenous morphine produced inside body morphine is an opiate opiates were used for pain relief analgesia opiates are addictive Morphine produce dreamy state and analgesia became used extensively in medical care ln civil war many treated with morphine and it led to huge addiction problem within men of the US Bayer company came up with a nonaddictive analgesic l heroin clearly this became disused 1940s Demerol created also addictive Now there are vicodin percocet codeine Must be opiate receptors in our body radioactively labeled morphine to see where it went l gut uterus vas deferens speci c places in spinal cord and brain these areas are responsible for pain perception Bound to place in limbic system emotional components of pain are feelings like fear and anxiety Body must be producing molecules similar to morphine this is what endorphins are 1975 Scotsmen discovered some short peptides which they referred to as enkephalins have profound opiatelike effects Peptides that were a bit longer with discovered endorphins Collectively ALL morphinelike peptides are referred to as the ENDORPHINS ln pituitary gland a long peptide Blipotropin and endorphins are released into bloodstream as hormones l endorphins are a natural way of relieving pain analgesia Endorphins work in the immune system psychopathology A Mechanism Enkephalin peptides neuromodulators modulates the amount of neurotransmitter that gets released by the cell Presynaptic inhibition 91614 Hormones 1 Hormones A Hypothalamus produces neuropeptides that control pituitary gland master gland critical in control B Pituitary gland hangs of brain and controls lots of hormones 1 lnfundibulum connects hypothalamus to pituitary 2 Anterior lobe adenohypophysis neurons at base of hypothalamus produce peptides that get secreted into network of capillaries found at base of hypothalamus and travel though infundibulum to pituitary through closed loop system neuropeptides activate cells in anterior pituitary and tells it to secrete pituitary hormones and they go into bloodstream travelling downstream to stimulate cells in glands to release their hormones 3 Posterior lobe neurohypophysis magnocellular neurons huge neurons in hypothalamus produce hormones nal product and hormone is transported through axons of these neurons and these axons go through infundibulum all the way to posterior pituitary when neurons are appropriately stimulated they release the hormone that goes through bloodstream and seeks its target 4 Feedback loops Hypothalamus controls pituitary l releases pituitary hormones into body travel to glands into body glands release hormones into body these feed back to pituitary and hypothalamus can subsequentially produce more hormone Most of the feedback is negative feedback too much hormone in body feedback to shutdown production Can use drugs to use this feedback to a desired effect if not under supervision can screw it up C Hormonal systems anterior ON PAPER D Hormonal systems posterior ON PAPER E Mechanisms of hormone action Peptides and amines 1 Second messenger system hormone receptor on cell is coupled to a Gprotein which then activates an enzyme often adenalate cyclase which causes conversion of a chemical into a second chemical often ATP l cyclic AMP Quick mechanism to regulate the cell Hormone is 1St messenger cAMP is 2nOI messenger 2 Steroids estrogen progesterone testosterone cortisol Lipid soluble can cross the membrane which is made of lipids and steroids get into cell where it binds to a receptor and this steroidreceptor complex works on the nucleus to affect protein synthesis Slow mechanism hours days weeks F Comparison between hormonal and neural communication Hormonal done through bloodstream broadcast communication slow communication graded in strength more hormones mean stronger message communication involuntary communication Neural carry neural information through neurons precise and localized communication fast communication allornone communication voluntary communication can choose to move a limb BUT both systems work together hormones feedback to in uence nervous system and nervous system feeds back to hormones 91814 Writing the Brain Developmental Neurobiology 1 Development of Gross structures A Embryonic blastula hollow ball forms during development after conception divides in three layers I 1 Endoderm become internal visceral organs 2 Mesoderm becomes skeletal muscle and bones 3 Ectoderm becomes skin and nervous system B Neural plate neural groove neural crest Neural plate forms from attening out of ectoderm Neural groove due to infolding in plate Neural tube infolding comes together to form a tube all cells in brain and spinal cord come from this Primary vesicles Front forebrain ie cortex and diencephalon Middle midbrain Most caudal hindbrain Rest of tube in the spinal cord Neural Crest extra bit of ectoderm that gets pinched off all cells from peripheral nervous system come from this C Differentiation in the beginning cells are undifferentiated They proliferate then migrate and lastly differentiate 1 Prosencephalon 2 Mesencephalon 3 Rhombencephalon 2 Genesis of neurons cellular development Ventricular zone of brain is closest to the ventricals at the base of the brain Marginalpia zone is on the outer portion A Proliferation an undifferentiated cell in ventricular zone reach an arm up to the surface pia zone and nucleus of the stem cell climbs up the arm to the pia surface This movement triggers the cell to duplicate its DNA Nucleus moves back down to ventricular zone and stem cell retracts its arm This is the signal for the cell to divide 1 Stem cells undifferentiated cells stays at ventricular surface 2 Daughter cells cell with same DNA as stem cell that divided B Migration after division daughter cell migrates away to new location Daughter cells migrate by wrapping themselves around a scaffold that are laid down by radial glial cells these extend arms up through the brain that provides a scaffold for a daughter cell to wrap around Glial cell retracts after daughter cell reaches its destination and it starts all over C Cell differentiation daughter cell differentiates when it arrives at destination A neuroblast grows processes called neurites One of these neurites becomes the axon and all others become dendrites Neuroblast would differentiate regardless of where it is so it is not dependent on signals in environment It was programed shortly after birth Cell s fate is speci ed by the environment around it shortly after it s born This programs the cell and determines fate Fate is dependent on the time that the cell is born because chemical environment is always changing Radioactive labeled thymidine can use to see what happens to a daughter cell after it is born Cortex builds itself from the bottom up In humans all cortical neurons are born this way between 5th week and 5th month of gestation once born neurons do not reproduce very well Some neurogenesis new production of neurons occurs but not much 3 Genesis of connections pathway development A Pathway selection target selection address selection all these pathways are critically dependent on cell communication cell to cell contact cell secretions contact from diffusable molecules from a distance away Pathway selection as neuron is growing it needs to choose a pathway Target selection needs to choose a general region to aim for Address selection chooses an exact location in the region to reach B Axonal growth great model for understanding this process 1 Growth cone at the tip of the apparatus that is critical for growth specialized structure that s designed to help neuron elongate itself and selec proper pathway to grow 2 Lamellipodia sheet of membranes at the end of the growth cone that oscillate 3 Filopodia spikes that stick out from lamellipodia and probe the environment allows growth cone to pull itself forward 4 Extracellular matrix a scaffold of proteins in between cells produced by glial cells This is what the growth cone grabs onto to grow Sometimes ECM is really thick that makes it hard for growth cone to grow Growth cone produces proteases and these eat through the ECM allowing the cone to grow through it C Pathway formation 1 Laminin sticking out of ECM are these guide postsquot growth cones only grow where there are laminins cell adhesion molecules Not all are attractive some are repellent molecules in ECM will repel growing axons this is how the cone knows which direction to go 2 lntegrins proteins that stick out of lopodia are sticky grab onto laminin cell adhesion molecules 3 Cell adhesion molecules CAMs the laminins and integrins can stick to one another 4 Chemoaffinity hypothesis concept that there are molecules that control where the cone should grow and connect Roger Sperry did some studies looking at development of nervous system using amphibians bc they can regenerate neurons and tissues Severed neurons connected to eyes and rotated eyes 180 degrees and let frog regenerate the neuron connections The frog jumped the opposite direction of where his prize was Neuron formed to the exact same place as before even though eye was upside down Neural connection seeks out same target regardless of where target is experiment where frog s belly skin put on back and back skin put on belly when back is tickles frog scratched its belly 5 Netrins diffusible molecules that attract growing neurons attractant diffusible molecules Another way in which neurons can be sent in one direction or another D Synapse formation growth cone has reached its target address and it now forms a synapse 1 Agrin Growth cone arrives at nal destination It secretes agrin and it crosses synaptic space and binds to agrin receptor on postsynaptic cell Gprotein coupled receptors When activated it signals to cell to produce neurotransmitter receptors Receptors insert into membrane of post synaptic cell This cell sends message to growth cone and opens calcium channels where calcium ows in causing cone to collapse This cone becomes axon terminal Signal sends for cell to start producing neurotransmitters These ow to the terminal and you now have a functional neural cell 4 Elimination of extra cells and synapses A Naturally occurring cell death we overproduce cells and neurons and we need to reduce the amount that are created through this method This is due to competition for lifesustaining molecules ie growth factors 1 Trophic factors neurotrophins growth proteins ie nerve growth factor reason why naturally occurring death must occur only so many resources Target cells secrete only limited amounts of these lifesustaining molecules The more active cells take up more of these molecules Cells that aren t used don t take them up and these cells die 2 Apoptosis method of death for the cells that do not receive the growth factors This is a genetic programming for cell death 5 Activitydependent synaptic rearrangement brain has a capacity to rewire itself and change synaptic connections as a function of early experience There are windows of time when the brain is very plastic and based on experience the brain can rewire itself A Critical periods of development the windows of time in which brain can rewire itself Hubel and Weisel discovered that in cerebral cortex cells are organized into columns based on their functions One of these columns is referred to as ocular dominance columns cells that get input switching off from right eye and left eye Took newborn kittens and shortly after birth they put an opaque contact in one eye Due to this change the ocular dominance columns changed dramatically columns corresponding to good eye expanded and ones corresponding to bad eye shrunk A rapid dramatic rewiring of the visual cortex occurred based on early experience to compensate for change in sight If you do this over 6 weeks after birth the ocular columns will not change meaning there is a critical period B Why do critical periods end When puberty ends the brain has become an adult brain and the critical periods end Critical periods need to end because some things need to persist in order to survive ie storing and retrieving information If brain continues to rewire lose important functions C Rewriting the brain after injury attempting to regenerate brain tissue in medicine to x problems in the brain If you stick stem cells in a brain they are not surrounded by the same environment so signals are different and they wont necessarily differentiate into the right type ofceH
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