Neurons and the Resting Potential
Neurons- parts and diease
Diffusion and Electrical Forces
- Most synapses end on dendrites
- Special receptor protein on cell membrane bind a NT Don't forget about the age old question of What is the meaning of the iron curtain in history?
- Shape + density of spines determines strength of interaction - Spines change with brain development and learning
- Extent of spine abnormality correlates with intellectual impairment o Ex. 1 General intellectual impairment (dendrites are long, spindly and sparse)Don't forget about the age old question of What are the characteristics of the watson and crick dna structure?
o Ex. 2 Fragile X syndrome (long, dense spines)
If you want to learn more check out What did james chadwick do to discover the neutron?
Key Functions of Organelles in Soma
2 Key Functions
1. Protein Synthesis
DNA (in nucleus within soma) -- (transcription)----> mRNA – (translation)---> protein
- Ribosomes (protein factories) If you want to learn more check out What are the four major symptoms that can help identify psychological disorders?
- Rough ER and Golgi
- Currency= ATP
- Krebs cycle in mitochondria
triphosphate (ATP)- 3
phosphate groups, when you
have a chemical reaction
where you lose one, you
release energy (conversion to
ADP releases energy)
- Scaffolding proteins affect neuron shape and function - microfilaments We also discuss several other topics like What are the two types of balance, and explain what they are?
- Microtubule Associated Proteins (MAPs)
- regulate assembly and function of microtubules
- e.g. tau proteins- links microtubules (like pearls on a string) Alzheimer’s DiseaseIf you want to learn more check out Define marketing myopia.
- cognitive loss- memory loss. Confusion, cognitive decline - macro brain – cells die, sulci expand, gyri shrink
Amyloid Protein is normal in many cells.
Error leads to beta-amyloid or BA. Which is abnormal
- Amyloid plaques
- Neurofibrillary tangles
Alzheimer’s Disease Progression- B amyloid hypothesis
- BA clumping because- beta amyloids are sticky, make others stick to them, toxic to neurons
- BA clump into plaques
- BA triggers formation of tangles
- Something about Tau interaction with BA changes the shape of the Tau protein (hyper-phosphorylation)
- Changes shape + changes function -> can’t hold microtubules together, pearls fall apart -> neurons dies
- Leftover Tau = tangle = neuron gravestone
- Distorted Tau affects other neurons
- Mad Cow disease
- No ribosomes
- No protein synthesis
- most protein synthesizes in soma and is shipped to axon Anterograde- toward terminal – controlled by kinesin
Retrograde- away from terminal- controlled by dynein proteins
Disease and axoplasmic transport
Cold sores- HSV-1 (herpes simplex virus 1)
1. virus enters nerve terminal
2. retrograde to soma
4. STRESS= anterograde back to axon terminal
Disease -> rabies
- Animal bite- saliva infection
1. Retrograde to Soma
3. Cell Death
4. Virus infects other cells
5. Death- days to weeks
Glia- 50-100 Billion
- not just glue
- electrically insulate cells
- nourish cells metabolically
- perhaps involved in brain computations (signaling information)
Astrocytes- most common glia
- Fills spaces between neurons, “glue” function
- Regulates ion concentration around neurons
- Guide neurons in development (make sure they end up in the right place)
- Protect by taking up toxins
Oligodendroglia and Schwann Cells
- electrically insulate cell with myelin
- increase speed of electrical conduction down axons
- Oligo (CNS)- one cell body myelinates multiple axons - Schwann (PNS)- myelinates one axon
- Most not neuron tumor, glial tumor
(Glial cells multiply throughout life)
Resting Potential and Action Potential
The Neuronal Membrane at Rest
- no AP
- Potential difference- energy to push electrons through wire (voltage= potential difference)
* Potential difference- energy to drive ions (an ion is a molecule that has an electrical charge) across cell membrane
Inside of a typical neuron is 65 mV more negative than outside
Vm= membrane voltage or membrane potential
At rest Vm= -65 mV
Vm is determined by distribution of ions (inside vs. outside of cell)
100 (a lot inside)
- Action potential (AP) conveys info over distances in the nervous system.
- AP- for an instant, inside cell positively charged compared to outside. - AP code frequency and pattern
- AT rest, neuronal membrane steady potential difference of about -65mV
AT REST: cytosol in neuron NEGATIVELY charge with respect to extracellular fluid (potential difference of about -65mV)
ACTION POTENTIAL: cytosol in neuron POSTIVELY charged with respect to extracellular fluid
Frequency and pattern of AP= neuron’s code to transfer information
2. Depolarization beyond threshold, RISING PHASE (Na+ channels open, Na+ in, depolarize)
3. Overshoot- Vm reaches peak of around 40 mV- inside of neuron + charged with respect to outside
4. Falling phase- K+ out (delayed rectifier- potassium gates open 1 msec after), Na+ no longer coming in, hyperpolarize
6. Absolute Refractory Period
7. Relative Refractory Period
Firing Frequency of AP reflects magnitude of depolarization current. Max frequency is about 1000 Hz
When membrane = depolarized to threshold, the molecules twists into a configuration that allows the passage of Na+ through the pore.
- Does not open immediately =, delayed rectifier
- When the memebrane is depolarized, the subunits are believed to twist into a shaoe that allows K+ to pass through
- TTX- clogs Na+ permeable pore by binding tightly to a specific site on the outside of the channel (blocks all sodium dependent APs)
AP propagate in one direction, because the membrane just behind it is refractory due to inactivation of the sodium channels.
AP can be generated by depolarization at either end of the axon, can propagate in either direction.
1. Down axon
2. Across axon diameter
∙ The greater the axon diameter, the greater the velocity (Here’s why: https://www.khanacademy.org/science/health-and-medicine/nervous system-and-sensory-infor/neuron-membrane-potentials-2014-03- 27T17:58:17.207Z/v/effects-of-axon-diameter-and-myelination)
∙ An axon with a larger diameter offers less resistance to the movement of ions down the axon, causing them to move faster through axon. - Smaller axons require greater depolarization to reach AP threshold and are more sensitive to being blocked by local anesthetics.
Why? With smaller axons, more of the voltage sodium channels must function to ensure AP doesn’t fizzle out.
Myelin + Saltatory Conduction
- APs jump from node to node= saltatory conduction
Nodes of Ranvier- voltage gated Na+ channels concentrated in membrane of nodes
Electrical- two cells come very close together, connexons come together, become gap junctions (used by glial cells)
Electrical and Chemical Communication
Types of Synapses
a Between axon and dendrites- AXODENDRITIC
b Between axon and cell body- AXOSOMATIC
c Between axon and axon- AXOAXONIC
d Between motor neuron and muscle cell- NMJ Neuromuscular junction
What happens at the synapse?
Electrical signal (AP) Chemical Signal (NT) Electrical Signal (de/hyperpolarization)
1. Synthesis and Packaging
2. Release of NT
3. Action in postsynaptic cell
4. Termination of signal
Terminal bouton materials - into vesicles
Amino Acids Transmitters
- Norepinephrine (NE)
- Epinephrine (Adrenaline)
Requirements to be considered a NT…
- Serotonin (5-HT) - Acetylcholine
- Substance P
- Neuropeptide Y
1) NT is synthesized by a biochemical process and stored in vesicles 2) Electron Stimulation causes release
3) Elicits effect
4) Method of termination
Amino Acids are basis for all NT
NT are either…
1. Amino Acids themselves
2. Amino Acid derivatives
3. Peptides- strings of Amino Acids
Examples (from Simplest to more
1. Glutamate ------(glutamic acid
decarboxylase enzyme) --
a. 1 ezyme converts 1
substance into another
b. 1 precursor, 1 product
9. Acetyl CoA + Choline --- ( choline (ChAT)
acetyltranferase) - Ach +CoA
a. 1 enzyme converts 2 substances into
13. Tryptophan ---- (Tryptophan hydroxylase) - 5-HTP --- (5 HTP
decarboxylase) - 5-HT Serotonin
b. More than 1 enzyme involved
43. Tyrosine ---(Tyrosine Hydroxylase) - DOPA ---
(Dopa decarboxylase) -
Dopamine ----(Dopamine B hydroxylase) --
44. (4 Enzymes involved, 3 NT made along the way)
45. 46. 47. 48.
49. In the above cases, everything needed for synthesis is found in terminal bouton BUT Peptide ( string of amino acids) NT synthesis different
51. Where are proteins made? Nucleus of cell
52. DNA(coded in genome) –(transcribed into mRNA) RNA – (translated into a protein by ribosomes) protein
53. Peptide bonds attach amino acids together
55. How are NT packaged
56. Energy needed to push NT into vesicles against concentration gradient.
58. Proton Gradient- NT transporter uses protein gradient to drive concentration of GABA into vesicle
61. Dale’s Principle
62. 1 neuron = 1 NT
63. any given neuron will only make 1 NT
64. But what about catecholamines?
65. Along pathway of neurosynthesis there are 3 (dopamine, NE, Epinephrine)
66. If cell is genetically programmed to be dopaminergic, it won’t make NE and Epinephrine. Pathway stops at dopamine.
68. So Dale’s principal holds to an extent based on genetic programming
70. Tight Regulation
71. Norepinephrine Terminal Bouton
72. End Product Inhibition (Feedback Inhibition)
73. Think of Catecholamine synthesis/pathway as assembly line. 74. Rate of production is dependent on slowest person in the lin. 75. Slowest person = rate-limiting
76. You can control how much and how fast you make your product by controlling the action of the rate-limiting enzyme, usually the first enzyme.
78. Excess NT (Norepinephrine in this case) leaks out and feeds back and inhibits the enzyme telling system not to make any more NT, there is NE production stops
80. How are peptides packaged?
1. DNA in nucleus mRNA is sent out into cytoplasm
2. mRNA grabbed onto by ribosome
3. Precursor peptide (large protein, not yet NT) is synthesized in rough ER (ribosome makes the protein)
4. Protein moves to loomin of ER, buds off into Golgi apparatus 5. In Golgi Apparatus peptide NT can be chopped up into smaller active pieces
6. Packaged into secretory granules
7. Transported down axon by axoplasmic flow
8. Once it ends up in terminal bouton it matures in synaptic vesicles 9. Synaptic vesicles stored in terminal bouton
84. Peptide NT have much higher molecular weight dense core vesicles
86. Release of NT
87. Otto Loewi
88. 2 Frog Hearts
89. Vagus nerve goes into heart- If stimulated, beating slows down 90. Vaggusstoff Acetylcholine
91. Accelerancestoff Epinephrine
92. (balance between acetylcholine and epinephrine controls heart rate)
94. When AP arrives at Terminal Bouton, vesicles close to membrane FUSE with itand release contents into synaptic cleft
96. There are proteins involved in this process
97. SNARE proteins- trap and hold the vesicle
a. V-snares- found on the vesicle
b. T-snares (target snares) found on inner leaflet
100. Synaptotagmin- calcium sensing protein
1. When AP arrives at Terminal Bouon, there are voltage gated Ca++ channels that pop open
2. Calcium rushes into the cell, binds to synaptotagmin
3. Vesicle slams down onto the membrane of the terminal buton and fuses with iy
4. NT released into terminal bouton
102. Release of Peptides
103. Voltage- gated calcium channels and vesicles
104. In case of peptide NT, calcium channels are farther away from where vesicles are anchored
105. More electrical stimulation required.
107. Action on Post-Synaptic Cell
108. Receptor molecules on Post-synaptic cell recognize very specifically their individual NT (lock and key)
109. Chemical Signal interaction with post-synaptic cell ultimately alters post0synaptic ell to change membrane potential
111. How rapidly membrane potential changes in post synaptic cell… 112. Fast-milliseconds
113. Intermediate- seconds
114. Slow- seconds to minutes
115. *depends on mechanisms of receptive signaling 116.
117. Which direction?
119. Depends on the ion whose permeability hs changed (Na+- depolarize, K+ hyperpolarize, l- hyperpolarize, Ca++ depolarize) 120.
121. Fastest- Ligand (NT) gated ion channel
122. - NT binds in synaptic cleft, changes confirmation (shape) so hole in the middle opens
123. Depending on ion selectivity of hole it will let ion flow 124.
125. Acetylcholine will usually gate Na+
126. Glutamate will usually gate Na+ or Ca++ 127. GABA will usually gate Cl-
128. Glycine will usually gate Cl
130. Many Ligand-Gated Receptors have subtypes
131. Glutamate (has 3 different subtypes)
1. AMPA receptor
2. NMDA receptor
3. Kainate receptor
132. G-protein coupled receptors (GPCRs)
- Single polypeptide chain
- Go through membrane 7 times
- NT related substances- Major NT that will activate / act through GPCR
o Acetylcholin e
o Glutamate o GABA
o Serotonin o Dopamine o Norepinephr ine
o Enkephalin o Cannabinoid
- Guanine-Nucleotides 134.
137. *GDP attached to Alpha
1. NT released into cleft, bind to receptor
2. Changes shape of receptor, gains affinity
3. GTP _> GDP exchange reaction
4. GDP pops off and is replaced by GTP
5. Beta and Gamma always stay together
6. Activated GTP- bound G-protein splits
7. GTP-ase converts GTP GDP by removing
one of the phosphate groups
8. GDP then inactivates alpha subunit
9. Re-associates beta gamma
147. 10. Turns of activation
155. Two things can happen that will alter the activity of the post synaptic cell
- Direct effect
- G-protein alpha subunits acts through enzyme enzyme makes other chemical messengers in the cell
158. Direct G-protein signaling
159. Muscarinic/ Acetylcholine Receptor
1. Beta-Gamma floats of and interacts with potassium channel, 2. opens it,
3. potassium flows out of cell,
4. membrane potential hyperpolarizes
5. (Acetylcholine chemical signal converted into electrical signal) 161. Takes seconds vs. milliseconds of ligand-gated receptors 162.
169. Second Messenger Cascade
1. NT binds to receptor
2. GTp- GDP exchange
3. Alpha-subunit buds off
4. Alpha subunit interacts with enzyme
5. Enzyme produces intermediate chemical second messengers 173.
174. EX. Adenylyl cyclase system
179. Protein Kinases
- Protein kinase takes ATP, removes terminal phosphate from ATP (A-P-P P A-P-P)
- Places terminal phosphate on the protein, changing its activity (activate it, inhibit it, activate it, close it, etc)
- Process is called phosphorylation
- Phosphatase reverses this process
181. Cyclic AMP Signaling System
184. Receptor- G- protein - coupled receptor (GPCR) 1. G-protein
o Gs (or Gi) alpha I inhibits adenylyl cyclase 2. Effector Enzyme
o Adenylyl Cyclase (AC)
3. Substrate of effector enzyme
o Adenosine triphosphate (ATP)
4. Second Messenger
o Cyclic AMP (cAMP)
o Protein Kinase
o cAMP- dependent protein kinase (PKA)
189. Phosphoinositide Signaling Team
190. Receptor- GPCR
191. G- protein- Gq
192. Effector Enzyme: Phospholipase C (PLC)
193. Substrate o Effector Enzyme: (PIP)
194. Second Messengers: DAG, IP3, Ca2++
195. Intermediaries: IP3 receptor, ER (endoplasmic reticulum) Calmodulin (CaM)
196. Protein Kinases: PKC, PKA (calcium/calmodulin- dependent protein kinase)
198. Opening a sodium channel or calcium channel results in a small depolarization of the cell. These small depolarizations are… 199.
200. EPSP’s (excitatory post-synaptic potentials)
- Opening a channel for chloride or potassium results in a small hyperpolarization
201. IPSP’s (inhibitory post-synaptic potentials)
203. Synaptic Integration
204. Cell has to collect all of its input in its dendritic tree and send that message to the spike initiation zone.
206. Integrate all input and make a determination
208. Synaptic NTransmission Quantal
209. Each packet of NT released from a vesicle is able to depolarize the post-synapses membrane by some fixed amount – Mini’s add up! 210.
216. Types of Integration
219. Length Constant- a measure of how far depolarization will spread 220.
221. Increasing the Length Constant
225. Passive vs. Excitable
226. With an excitable membrane, voltage gated sodium channels spread depolarization further
229. An inhibitory synapse can cancel out excitatory synapse, the AP never reaches hillock because negated.
231. Terminaton of Singaling
232. NT removal from synapse
233. 1. Diffusion (not very efficient)- used by peptides
2. Degradation- chemically degrade the NT so no longer active 3. Reuptake- take NT back up to terminal bouton, NT repackaged, very little is wasted
235. Calcium- How to Get Rid of It
236. ATP-ase in ER membrane hydrolyzes ATP to drive it back into the ER (storage depot for calcium)
237. There are also ATP-ases in plasma membrane where calcium can be pumped out of the cell
- Also requires ATP hydrolysis
239. Phosphorylated Proteins
- Protein phosphatases come in and remove a phosphate group from proteins
243. Brain Anatomy
245. Spinal Cord- grey matter- mostly neuron cell bodies 246. White matter- mostly axons, outside in the spinal cord 247.
- Structural support and protection of brain
- Brain is floating in a bag of fluid
- Cerebrospinal fluid- fluid that inflates the bag
- Ventricles- generate cerebrospinal fluid
252. 253. Development of Nervous System
- We all start from single cell, a fertilized egg
- Cell multiply in numbers
- Subdivide labor- Differentiation
255. Neural Plate
- Primary Layers
o Mesoderm- on inside
o Endoderm- inside wall
o Ectoderm- on outside- skin and nervous system develop from this 256.
259. * Ectoderm pinched off in (d) is the neural tube that will form spinal cord and brain
260. Neural crest will form peripheral system that’s outside of bone. 261.
- If neural tube is not zipped up/fused properly in caudal direction it can lead to spina bifida, some or more of spinal cord exposed in back - If brain doesn’t zip up in rostral direction- brain will not develop anencephaly (no brain) FATAL
269. Diencephalon (Thalamus,
270. Telencephalon (cortex,
273. Tectum- dorsal- roof
(contains colliculi, hills)
274. Tegmentum- ventral- floor
277. Rostral- cerebellum
278. Caudal- Medulla
283. Cell proliferation and Migration
285. Where are these cells coming from?
286. Neurons are born from stem cells.
287. Stem cells are localized around ventricles.
288. The original ventricle was in the neural tube.
289. The tube pinched off from ectoderm and there was a fluid filled space down the middle of the tube.
290. At that zone, more and more neurons are added. 291. They develop, differentiate and crawl away to their final location (migrate)
292. Most cells born between 5th weeks and 5th month of gestation and aggressively pruned away.
293. Apoptosis- Programmed Cell Death
294. Are new neurons born in adults?
295. Mew research says, YES.
297. Experiment to show elderly constantly generate new neurons throughout life.
1. Dividing cells need to be labeled
2. DNA in nucleus has to be copied to divide
3. In animal studies, a compound (BrdU) (a version of uridine that is incorporated in DNA that is being replicated.
4. Any daughter cell will forever have this compound in DNA 298. *Glial cells- this compound was expected in glial cells because they are always dividing. Most cancers in brain are gliomas or glial cells that divide out of control but they also found neurons!
299. 5. Subjects were people who were terminally ill. 300.
301. There were a few hotspots in the brain where neuron generation was happening
- Part of olfactory system
302. (Both brain areas adjacent to ventricles)
304. There is programmed cell death (Apoptosis) in these areas to keep brain volume within tolerable range.
306. How do you increase neurogenesis?
- Physical exercise (shown with rats on a treadmill)
- Learning (rats given novel stimulus)
- Death of existing neurons (MS, Alzheimer’s, Huntington’s, Stroke)
o Not nearly enough to keep up with the amount of cell loss - Human study: Neurons positive for cell proliferation marker Beta III tubulin seen in brain area surrounding stroke.
309. Locating Major Structures in Simplified Version of NS 310.
311. ALL IN ONE!
320. Fluid in 3rd ventricle funnels into cerebral aqueduct and empties out into 4th ventricle.
325. Vision: In a nutshell
326. Reception of light by retina in each eye.
327. Processing of information by retina.
328. Optic nerve transmits information to a relay station called the thalamus
329. Thalamus inputs sorted.
330. Thalamus inputs begin to be processed
331. Information flows to visual cortex
332. Visual cortex extracts features from scene: shape, color, distance, motion
334. Information flow in cortex is both sequential and parallel 335.
338. Electromagnetic radiation
339. Light lies on spectrum
342. You can characterize different points along the spectrum by the length of the waves at the point.
344. Light- longer than x-ray but shorter than microwaves
345. Infrared- can't be detected by eyes (used by TV remotes to send signals)
346. Ultraviolet- UV, eyes not sensitive to this
347. Visible light- part of spectrum our eye can actually see 348.
349. Photons- particles, minimum unit of light
351. The Eye
352. Light collected by lens, changes its shape to focus the light by the action of ciliary muscles
353. Light recorded on retina by photoreceptors
354. Photoreceptors convert light energy into neuronal activity 355. Transmits image signal down optic nerve
356. Eyeball pivots by action of oculomotor muscles
357. Eye adjusts to differences in illumination by controlling pupil diameter 358.
Tightly packed at the center- fovea (higher resolution at center) 360.
362. Retinal Layers
365. Three Main Functional Stages, Two Synaptic Layers 1 Photoreception (deeper layer, farthest from where the light enters) 2 Internal Transmission
367. Light detection occurs in photoreceptors
368. Light signal transmitted synaptically and processed by a series of interneurons
∙ Bipolar cells
∙ Retinal Ganglion Cells
370. At each stage there are laterally connecting cells
∙ Horizontal and amacrine cells (allow synchronization and integration of input)
372. Axons of retinal ganglion cells bundled into optic nerve which distributes visual information in the form of parallel action potentials that code for each visual feature detected
374. Sent on to deep brain regions.
380. Rods and Cones
382. Both have inner segment, synaptic terminal, outer segment 383.
384. Rods- low light levels
386. Cones- higher light levels and detection of color
388. Photo- Transduction
389. Conversion of Electromagnetic energy --> To Chemical --> To Electrical
390. 1 Photons enter the eye
2 Fall onto retina
3 Photons absorbed by photoreceptor cells in the outer segment 4 Photons transduced into chemical energy
5 Chemical signal to an electrical signal through change in membrane potential in the outer segment
6 Electrical to chemical at synaptic terminal
392. Rods outnumber cones in retina by about 20 to 1
394. Photo-transduction converts light energy into changes in membrane potential in the photoreceptor cells
396. Photoreceptors, rather than reacting to a chemical ligand, react to electromagnetic energy in the form of photons
398. Certain molecules can absorb photons at particular at particular wavelengths and this causes the molecule to change shape.
400. Rods- conversion of light to chemical signal- protein called rhodopsin 401. Rhodopsin= G-protein coupled receptor = opsin, ligand = retinal 1 Binding of a ligand to a receptor
2 activates G-proteins in the membrane,
3 stimulates generation of cytoplasmic second messenger molecules 4 Second messenger molecules change the conductance of ion channels, 1 changing neuronal membrane potential
1 Rhodopsin- unlike other GPCR's, its ligand retinal is already tightly bound to the GPCR protein backbone, opsin
2 When photon is absorbed by retinal, the shape of retinal changes, 1 change in opsin backbone
1 Causes activation of G-protein transducin,
2 changes in cytoplasmic concentration of second messenger molecules cyclic GMP by action of enzyme cGMP phosphodiesterase 3 Leads to modulation of cGMP- gated ion channels and changes in membrane potential
403. In the dark, cGMP opens sodium and calcium ion channels in outer segment- depolarizing cell after sodium influx
404. Release NT in dark
406. In light, cGMP depleted, closing ion channels, hyperpolarizing the cell
407. Stop releasing NT in light
410. Amplification- each activated rhodopsin can activate hundreds of G proteins, can activate many phosphodiesterase's, generate thousands of cGMP molecules
411. This means visual system can detect as little as a single photon 412.
414. Color Vision
415. Cones- can perceive finer detail and more rapid changes 416.
417. Each type of cone has a different visual pigment able to sense different wavelengths of the light spectrum
A S- cones (short wave cones)- detect blue light
B M-cones (middle- wave cones)- detect green light
C L- cones (long wave cones)- detect red light
420. Spectral sensitivity and difference in the signals received from the three cone types allows the brain to perceive a continuous range of colors 421.
422. Cone receptors- all contain a GPCR protein called photopsin/ cone opsin
423. Photopsin- able to transduce light
425. Photopsin portein differs by a few amino acids for each cone type color sensitivity
427. Representing a range of colors- spectral sensitivity curves overlap 428. Different wavelengths of light elicit different levels of responses 429.
430. Tri-chromat- three color vision
432. The color we perceive depends on the overlap of the spectum of the light with the absorption of the cones across all three cone types 433. Metamers- different patterns that elicit the same percept 434.
437. Deuteranopia: red- green color blindness, individuals lack M-type cones and and green are perceived the same way because they excite thr remaining cones identically
439. Night vision= scotopic vision- rods far more active than cones 440. Day vision- photopic vision
443. How does retina generate a visual image
446. Three main specialized cellular layers:
448. Outer nuclear layer- contains rods and cones- Photoreception 449. Inner- nuclear layer- contains interneurons (bipolar, horizontal, amarcine cells)- Internal Transmission
450. Ganglion layer- contains ganglion cells- Output neurons that generate action potentials, transmitted via optic nerve to the brain
452. Ganglion cells- only cells in the retina capable of generating action potentials
453. All other cells (except amacrine cell types)- respond to stimulation with graded changes in their membrane potential
454. Detection of graded changes in membrane potential harder to record and study.
456. Kuffler experiements- used cats, able to map region of the screen that affected the activity of the neurons he was recording from- neuron receptive field
458. Receptive field- the region of visual space that when stimulated, evokes a response in the cell
459. For retinal ganglion cells, Kuffler was able to show that the receptive field was organized in a center surround organization
461. In some cells- response recorded when center of the receptive field was illuminated
462. Response stopped when part or all of the surround was illuminated as well
464. Work in the reciprocate- off center-surround organization 465.
468. ON Center
469. Cells -
470. OFF Center
472. Ganglion cell responses are built from the interactions of the upstream bipolar and horizontal cells.
474. Each photoreceptor and interneuron can be part of the center and surround of a receptive field of different retinal ganglion cells
476. Most retinal ganglion cells respond better to small spot of light than to diffused light because center surround flied enhances sensitivity to edges and contrast
479. Retinal Circuit
480. Direct pathway of information- input photoreceptor cell through a bipolar cell to an output retinal ganglion cell,
481. Lateral pathway- in each synaptic connection btwn cell layers, the neuronal responses are modulated by the lateral connections of horizontal and amacrine cells.
483. Information flow from photoreceptors to bipolar cells 1 Photoreceptors release NT when depolarized (main NT is amino acid glutamate)
2 Photoreceptors are depolarized in the dark and hyperpolarized in the light 3 Direct Pathway
a Based on responses to glutamate released by photoreceptors, bipolar classified as ON or OFF cells
i In OFF bipolar cells- glutamate- gated cation channels mediate a depolarizing EPSP aafter sodium influx
ii In ON bipolar cells- G-protein coupled receptors respond to glutamate released by photoreceptors via hyperpolarization
∙ (ON or OFF for bipolar cells means cells depolarize in response to light off (more glutamate) or light on (less
iii Each bipolar cell receives direct synaptic input from a cluster of photoreceptors
iv Each bipolar cell also connected via horizontal cells to a ring of photoreceptors that surround the central direct cluster
v The receptive field to which these cells respond consists of two parts ∙ Circular central area of retina providing direct input from the photorecptorsm and a surrounding area of retina providing
indirect input via horizontal cells
484. Retinal ganglion cell output to optic nerve
486. Things to Know
488. LGN- passes information about color, contrast, shape, and movement on to the visual cortices
489. Superior colliculus- controlling the movement and orientation of the eyeball itself , an example of retinotopy because the arrangement of cells in the colliculus is identical to that of the corresponding cells in the retina 490. Pretectum- controlling the size of the pupil
492. Two major visual pathways
1 Retina to optic nerve to brainstem
2 Retina to optic nerve to lateral geniculate nucleus of thalamus to primary visual cortex (area 17) to temporal and parietal cortices
494. Decussation- some axons from optic nerves cross over to the other side of the brain: half of each retina's visual field is represented on each side of the brain
497. ipRGCs- contain melanopsin (photosensitive), send information to suprachiasmatic nucleus of hypothalamus, detect overalllight sensitivity, regulate circadium rhythms
499. Lateral geniculate nucleus organization- keeps visual info separate based on which eye it is from
500. Magnocellular layers in the lateral geniculate nucleus are in the bottom two layers and receive input from the M-type ganglion cells.
502. Parvocellular layers of the lateral geniculate nucleus are the top four layers and receive input from the P-type ganglion cells
504. Koniocellular cells in the lateral geniculate nucleus are in between layers and receive input from the non-M/non-P ganglion cells.
506. Corticofugal pathway- from the primary visual cortex to the LGN 507.
508. Primary visual cortex is in the occipital lobe.
510. Spiny stellate cells of the visual cortex- in layer IV
512. Pyramidal cells of the primary visual cortex- are in all layers, connecting to other brain regions
515. What are sounds?
516. We live surrounded by air, atmosphere is pressing on you, 100,000 newtons for square meter, keeping you from exploding
519. Pressure: force per unit area, pascal
520. Molecules in the air moving around with energies associated with temperature of the room
522. When an object moves in the air, it pushes on the molecules of air and creates a wave of molecules that move away from the pushing, when it retreats, the molecules are sucked back, near field- actual flow of the molecules
524. If you get much further away, the air molecules are no longer moving in a flow, movement makes a transition to become pressure changes, no net flow of molecules, molecules are instead condensing and expanding, far field compressions and rarefactions
526. Compression- air pressure higher from average pressure in room 527. Rarefied- a short distance away or short time away- atmospheric pressure lower than average
528. Space-time distribution of changes in density of air molecules
530. Aneroid barometer- reference pressure inside of it, measures atmospheric pressure
531. Weather fronts and temperature influence pressure.
532. Also measures pressure in relation to altitude
533. Aneroid altimeter- for airplane, on basis of air pressure, tells you how far you are from ground, as you go up, decrease in air pressure
536. Birds have lagena, organ in inner ear, sealed pressure chamber with a membrane over it and hair cells for measuring air pressure changes as manifested in movement of membrane. The lagena is an aneroid altimeter and barometer for the bird. Bird know its altitude as reflected by excitation of the nerve fibers that come fro the lagena.
538. Homing pigeon, not only aware of air pressure in terms of height above the ground, but also air pressure of relatively low frequency propagated pressure changes that can come from long distances. Thunder is a very strong, low frequency signal, a homing pigeon can determine a thunderstorm is approaching. Uses the lagena for navigation. We can't hear such low frequency sounds, we do not have a lagena.
540. We hear faster fluctuations.
542. A microphone is an air pressure measuring device which measures high frequency fluctuations of air pressure. It has a small hole in it to prevent low frequency pressure changes from moving to the microphone diaphragm. Adjusting the size of hole changes the frequency of sounds you hear. Principle of Mammalian Inner ear too.
544. Hertz pressure changes over time,
545. We normally hear sounds between 20 hertz, 20,000 hertz 546.
547. As sound pressure fluctuations move the diaphragm, voltage changes come out in the microphone and into a recorder. SUMMARY: Similarly, when sound pressure pushes ear drum in, a linkage of bones causes fluid to flow inside the inner ear and you get an electrical response, triggering the occurance of nerve spikes. Below average air pressure pushes ear drum out and pulls the bone linkages the other way, alters the flow of fluid inside the cochlea and the voltage that causes nerve spikes goes down and nerve spikes stop.
549. Sound Pressure
550. Sound Pressure Changes have two dimensions to them. 551. Intensity- amplitude of the sound pressure waves
552. Amplitude changes in pascals.
555. For higher frequency sounds, you are changing the number of cycles per second, number of events per second
556. Period- time interval between successive cycles
557. Amplitude- sound pressure change
559. No air= no sound waves
561. Recap: Atmospheric Pressure
562. Air Molecules are compressed and rarefied at source 563. Waves travel from source to ear drum
564. Ear drum moves back ad forth in synch
566. Sound is dissipated as it travels through the air by a molecular process described as friction. As the sound moves through the air, it warms the air because some of the energy in the sound is being transferred through the air thermally.
568. Under auditory system, we identify different speakers from the combination of frwequencies present in the sound, pitch of the sound carries most of the information about vowels,
571. 20 micropascals- 0.00002- lowest you can hear
572. 10-20 pascals- highest you want to hear
574. In going from pascal scale to dB scale you simplify the representation of the numbers
578. The Pinna
579. When the sound reaches the external ear, now we are talking about physiological, biological effects
581. The external ear begins with a horn-shaped pinna, which funnels down into the ear canal, internal auditory meatus, primary function: having a large receiving surface, focuses down on a much smaller diameter ear drum, aperture of the horn, or mouth of horn
582. External ear, the antennae for receiving patterns
584. Relative risk in being able to figure out what's going on in one direction vs not knowing there's a cat coming up behind you in the other direction, a solution to this illustrated in rabbit or deer, ears are large and can move, we have smaller external ears and are fixed, but we move our entire head to look at source of sound, automatic reflex steers head
586. Ear drum, tympanic membrane is the end of the external ear, the inside of the tympanic membrane belongs to the inner ear system. It has a function related to the movement of sound (vibrations from the air to the fluids inside the cochlea.
587. When the sound gets to the bottom of the ear canal it vibrates the tympanic membranes and that engages the middle ear ossicles (little bones) 588. Ossicles
589. Malleus or hammer, rotates around a center of gravity 590. Incus, anvil, has a curved shape, is attached to malleus, when malleus moves, so does the incus, the end of the incus is attached to a joint 591. Stapes, stirrup, has a circular footplate, inserts into fluids of inner ear, fluid travels along spinal cochlea until it finds a place where the freq of the movement of footplate and stapes matches the properties of basilar membrane
592. Basilar membrane varies in stiffness from very stiff at the base of the cochlea and very unstiff or compliant at spiral tip of cochlea
599. A very stiff structure won't vibrate except at very high frequencies 600.
601. Round window, thin, translucent memebrane, very compliant, when footplate of the stapes goes in, the round window goes out to releive the pressure, reciprocal movement by footplate of stapes and round window to relieve pressure
606. Black arrows above give a sense of the movement of things: the movement of the tympanic memebrane pushes on the handle of the hammer, or, the manubrium of the malleus, causing it to rotate
608. 3 things happening in system to increase sensitivity to hearing 1 Relatively large diameter or the aperture of your external ear compared to the small diameter at the base of the external ear system (diameter of tympanic membrane) amplification by 10
2 Tympanic memebrane much larger than the diameter at the footplate of the stapes, amplification process by gathering energy over the whole tympanic memebrane and concentrating it (pistum effect, delivering energy to small surface)
3 Length of handle of hammer and length of incus (a bit shorter) an improvement in force caused by the lever effect of the bones
611. Very dense, inelastic bones, high frequency sounds make it all the way into inner ear
613. Attached to the stapes is a muscle called the stapedius muscle, attached to the hammer handle is another muscle, the tensor tympani muscle
∙ When these muscles contract, they stiffen the bony structures of the middle ear system, reducing the sound going into ithe cochlea from the ear drum, (protective) when you hear a very loud sound, these muscles contract and
reduce the strength of the sound going into the inner ear, also, when you vocalize, the sound you are generating is not only going from larynx to the bone of the cochlea, but from the mouth to the ear,your voice is louder than you experience it to be because middle ear muscles (stapedius and tensor tympani muscle) contract (synchronous middle ear muscle contraction)
∙ Middle ear muscle reflex- you hear a loud sound and muscles immediately contract to impose the protective effect
∙ When footplate of stapes moves in and out, it introduces fluid flow in the fluid inside the vestibular system
615. Spiral Structure of the Cochlea
616. Human cochlea has about three and a half turns to it 617.
618. Stria Vascularis- privdes ions to operate the inner ear system (battery to the hir cells)
619. Scala (tube, spiral) vestibuli (up, closer to vestibular organ)- one of two big tubes, the one on top
620. Scala tympani- closer to tympanic memebrane
621. Organ of Corti- assembly of cells, organ for hearing, roughly similar to eyeball
622. Scala media- middle tube, only place on the body where you can find a strong electrical voltage
623. Perilymph- fills both scalas (vestibuli and tympani) surrounds the organ of corti
624. Reissner's membrane- separates fluid from both scalas 625. Endolymph- fills scala media
626. Tectorial membrane- network roof that reaches over the top of organ of corti, doesn't contain cells
628. Somatic Sensory System
629. Tuesday, October 25, 2016
630. 12:59 PM
1 Exteroception- something from outside world impacting the individual, using somatesensory system to analyze what is going on
a Mechanoreception (touch)
b Thermoreception (temperature)
c Nociception (pain)
631. *Intimate sensation
1 Proprioception (position)- Where am I in space? Important for planning movements
2 Enteroception (visceral sensory) (is my stomach full or empty, is my blood pressure rising?) Focused on what's going on within body)
Outline for SS system
633. Several sub modalities within somatic sensation
634. Those sub-modalities can be divided into:
a Protopathic (pain and temperature and itch) and
b Epicritic (touch and vibration)
636. Transduction Pathway- In order to be sensitive to something you have to transduce physical stimulus out in the periphery first and convert in into a change of membrane potential. (In visual system, more or less light going into the eye caused more or less depolarization of those photoreceptors)(In
auditory system, sound waves moves hair cells, opening and closing potassium channels)
638. Again… THE BASICS
1 Transduce physical stimulus out in the periphery
2 Send info into the CNS
3 Works way up into the thalamus
4 Relayed up into the cortex
5 Perception happens
640. Receptor subtypes (and receptive fields)
641. Receptor density and acuity- relationship between the two ∙ In visual system we saw the fovea has greater density of photoreceptors, larger number of ganglion cells, better acuity
∙ Auditory system- not as big a difference
∙ Lips or fingertips magnified in central maps, more acuity
o Sensory density and acuity
o Sensory fiber types and central projections
o Topographic mapping in the CNS
o Damage and disease of the SS system
o Nociception vs. Pain
∙ In visual system you have a 2D sensory surface looking out at the world, if you just map the machinery in retina, to areas in the brain and keep the register, you'll keep that 2D representation in the map
∙ In auditory system, map for tone, but no 2D surface sensing auditory stimulus, it was computed
∙ Somatosensory system, back to 2D surface, surface of the skin, axons from finger go to one area of brain, axons from wrist go to neighboring area of brain, good topographic mapping
645. Receptor Density and Cortical Magnification
∙ Does density determine cortical magnification (how exaggerated the representation of that body part is demonstrated in the brain) and acuity (i.e. central vision highly exaggerated in visual cortex compared to peripheral visual space)?
∙ What other factors may play a role?
647. Are Cortical Maps "Hardwired"
∙ Evidence from training
∙ Evidence from amputation
∙ Phantom limb sensations
649. Is Sensory Processing always bottom up?
650. Bottom Up is basically- From periphery, to central, to cortex, ultimately you are conscious of it
652. Some stimulus is applied to the surface of the skin, causes a change in membrane potential of sensory fibers in my finger, a change in the frequency of action potentials going into my spinal cord up to my brain stem, that gets relayed to neurons in the thalamus, then primary sensory cortex (S1) , then consciousness
653. If you inactivate that relay in thalamus, something could be pressing on finger and you could be unaware
654. Skin--- brain stem--- thalamus ---S1--- consciousness 655.
656. Top-Down would be anything that comes from the brain and influences the information as it attempts to go from the bottom up to your cortex (in visual system thalamic relay neurons, projections backwards from visual cortex)
658. Two types of skin
∙ Hairy skin
∙ Glaborous skin- lack of hair (lips, fingertips)
660. Hair cells very sensitive- Axon, hair follicle receptor wrapped around hairs follicles, stimulus stretches axons and causes action potentials 661.
∙ Some of the axon terminals are really close to the surface of the skin, like Meissner Corpuscles and Merkel's Disks
∙ Some are buried deep underneath like Ruffini's end-organs and the Pacinian Corpuscles
663. Meissner Corpuscles and Merkel's Disks- right underneath glabrous skin, playing important role in fine discrimination and two point resolution (differentiating coins in your pockets)
665. Somatosensory system- first system where receptive field described (multimodal- these cells sensitive to touch/temperature), easier to access and record a nerve extracellularly
667. Vallbo & Johansson
∙ Easy access to somatic sensory system, did many of these experiments on themselves
∙ Put needles through arm, mapped receptive fields
∙ System where following concept were described first
o Receptive fields
o Parallel processing
∙ Different receptors
∙ Different conduction velocities
o Topographic mapping
o Cortical Magnification Structures
689. Classes of Mechanoreceptors
690. Mnemonic devices:
691. Small and superficial- German- Meissner and Merkel 692. Pacinian, Ruffini- Italian- Large and deep
694. Property of Adaptation- change in presence of physical stimulus that is activating the cell the most
695. Pacinian corpuscle, for example, have fast adaptation- Response when pressure is applied, no response when pressure is constant, response when pressure is removed- fast adaptation
696. Merkel's and Ruffini's ending- respond all the way through 697. (in visual system phasic responses (turn light on, get big response initially and then it fades away) vs tonic responses (you turn the light on, it fires fast and then it keeps firing while light is on) 698. Meissner and Pacinian- Respond more when stimulus is changing 699.
700. Adaptations can develop in a number of ways:
∙ Circuits- a network of cells that excite and inhibit each other ∙ Could be built into membrane itself, depolarize the membrane, gets really excited but then some other current comes in, some molecular process inside the cell gets turned on, it shuts that down, fires a lot at very beginning and the slows down a bit.
∙ Mechanical properties of receptors out in the skin- look at Pacisnian corpuscles, axon contains stretch activated sodium channels o Surface of skin and axons
o Axon has voltage gated sodium channels in it, ready to go o If membrane potential depolarizes beyond threshold, its going to start generating action potentials
o There are also mechanically gated sodium channels (like with hair cells)
o If channel is stretched, sodium channels opening
o Action potential
o Little pressure gives little depolarization
o Pressing harder, fire AP at higher frequency
o Frequency of action potentials carries info of amount of pressure
o More pressure, more stretch, more action potentials because more sodium channels opening
o What can slow down the firing? Another mechanical process
o Pacinian corpuscles wrapped with layers and layers of gelatinous stuff on the outside
o If you get rid of the encapsulation, and you poke onto the cell, you'll see the membrane potential depolarize
o If you maintain pressure, gelatinous layers slide off to the side and relieve the pressure on the side of the axons
o When you pull it away you get a suction effect that draws the membrane in the other direction and you get another potential as a consequence.
702. Why do we have adaptation?
∙ Physical signal first present, you activate mechanoreceptors, aware, but a few hours later, no longer aware of watch on wrist
704. Why is vibration important?
705. Pacinian corpuscles
∙ have a characteristic frequency where most sensitive to stimuli ∙ On Y axis, looking at micrometers
∙ If stimulus frequency is less than 10 hertz, even a one mm poke is not enough to activate Pascinian corpuscles
∙ But if you are poking the skin in and out 300 times/ second, then one micrometer is enough
706. Meissner's corpuscles
∙ Different characteristic frequency
∙ 50 hertz
∙ Vibration- gives clues about texture
711. Acuity: two-point discrimination
712. Do you feel one point or two points
713. Acuity on finger 20X better than back
714. Maybe density of receptors 20X higher on finger than back 715. Maybe receptive field size 20X smaller
716. Cortical Magnifier 20X greater
718. If lower density receptors, tend to have larger receptive field 719. If higher density receptors, tend to have smaller receptive fields 720.
721. Primary Afferents
722. Afferent information going into the central nervous system, carried through a number of
723. different types of fibers
747. What are the differences?
748. Large diameter, high degree of myelination, fastest conducting 749. C- fibers- slow
750. Different kinds of info travel through different axons, some can afford fast, some slow
751. Why not make everything fast?
752. There's a cost associated with making everything fast, that doesn't make it worthwhile.
∙ Too many resources to make a big fat axons, wouldn't have enough space, cell bodies of axons that are really big are bigger, peripheral nerves would be huge
∙ Reflexes have to be really fast, but sometimes you can get away with a slower signal
784. Segmental Organization of the Spinal Cord and Dermatomes 785. Cervical - 8 segments
786. Thoracic- 12 segments
787. Lumbar- 5 segments
788. Sacral- 5 segments
790. Arms- cervical and thoracic
791. Legs- lumbar and sacral
792. There is significant overlap so you would have to cut several spinal nerves in a row before you'd end up with a dead patch of skin, where you can't feel anything.
793. A reinfection- affects one of these domains like in chicken pox --> shingles
795. First pathway
796. Dorsal Column- Medial lemniscal Pathway, carries epicritic information (touch and vibration)
∙ Comes in from the skin through dorsal root of the spinal cord ∙ Travels up the Dorsal column on the same side that it came in (ipsilateral) ∙ Dorsal column nuclei of medulla, first synapse, on the same side(ipsilateral) ∙ Axons coming out of dorsal column nuclei cross the nervous system (Decussate) in medulla (contralateral)
∙ Ventral Posterior nucleus (VP) of thalamus (contralateral)
∙ S1 of cortex (contralateral)
798. DCML Pathway- Epicritic, touch vibration
799. Spinal cord coming in, splits into dorsal and ventral (ventral is motor out, dorsal is sensory in)
800. Cell body sitting in dorsal root ganglion
801. All of primary somatosensory fibers are unipolar neurons, (cell body with one neurite coming out, the neurite splits, one end is out in periphery (fingertip) and one in medulla))
803. In spinal cord, information is ipsilateral
823. 824. 825. 826. 827. 828. 829. 830. 831. 832. 833. 834. 835. 836. 837.