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Neurobio I > Exam 2: Lectures 6-9 > Flashcards

Exam 2: Lectures 6-9 Flashcards

1
Q

neurons use both _____ and _____ signals to communicate w/ each other

A

electrical, chemical

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2
Q

electrical synapses

A
  • can think of it as one interconnected cell (still some space, but only 4 nm)
  • cytoplasm between cells is shared
  • gap-junction channels
  • agent of transmission is an ion current
  • almost no synaptic delay
  • bidirectional transmission (usually)
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3
Q

chemical synapses

A
  • 20-40 nm of space
  • cytoplasm is not shared
  • presynaptic vesicles and active zones + postsynaptic receptors
  • chemical transmitters
  • significant synaptic delay
  • unidirectional
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4
Q

electrical synaptic transmission is …

A

… rapid, w/ no time delay between neurons

  • current flows unimpeded between the neurons (neurons can be thought of as identical)
  • signals between the two cells virtually indistinguishable
  • typically, current can flow in both directions (non-rectifying)
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5
Q

gap junction hemichannels provide a …

A

… bridge, allowing direct communication between the two neurons

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6
Q

What molecules can go through gap junctions?

A

all ions and small metabolic and signaling molecules

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7
Q

ions that can go through gap junctions

A

all ions, Ca2+, Mg2+, Na+, K+, Cl-, bicarbonate, phosphate

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8
Q

small metabolic and signaling molecules that can go through gap junctions

A

amino acids, glucose, ATP and 2nd messengers (i.e. cAMP, cGMP, IP3, etc.), up to 2000 Da

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9
Q

how to distinguish electrical synapse vs. a chemical synapse

A
  • block Ca2+, if transmission isn’t blocked it is electrical
  • look for vesicles, block vesicle formation and see
  • dye coupling experiment (can see if dye can travel from one neuron to another)
  • gene expression (mRNA for gap junction gene expressed in the cell bodies of sensory neurons, can see gene on tissue surface w/ medicinal leech)
  • pharmacologic blockage or gene knockout (knock the gene out, and you no longer see the coupling)
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10
Q

Electrical synapses mediate _____ between various neuronal compartments

A

electrical coupling

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11
Q

properties and functions of electrical synapses

A
  • Rapid signaling
  • Reliable
  • Synchronous activity of many cells
  • Direct transfer of key small molecules
  • More prevalent during development
  • More prevalent in invertebrates
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12
Q

coordinate a rapid defense behavior in sea slugs

A
  • invertebrates are small animals (typically prey), need to be able to mount rapid defenses (escape)
  • sensory neuron connected to various motor neurons, these motor neurons connected w/ gap junctions (record at same time, neurons become indistinguishable)
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13
Q

chemical synaptic transmission

A
  • more abundant (usually a neuron has >10,000 to 150,000 synapses)
  • more versatile (fast/direct, slow/indirect; excitatory, inhibitory; short-term and long-term regulation, etc.)
  • no direct flow of current in between the cells
  • no direct physical connection between the cells
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14
Q

harnessing the parasympathetic nervous system

A
  • Sympathetic system prepares the body for energy expenditure, emergency for stressful situations (e.g. fight or flight)
  • Parasympathetic system is most active under restful conditions; counteracts sympathetic system after a stressful event and restores the body to a restful state
  • Vagus nerve stimulation slows heartbeat
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15
Q

discovery of chemical synaptic transmission (Otto Loewi)

A
  • Loewi had a famous dream the night before Easter Sunday of 1920 of how to discover chemical synaptic transmission
  • used a frog heart w/ the vagus nerve still attached (we know that if the vagus nerve is stimulated, the heartbeat will slow down)
  • added fluid secreted from heart #1 and added it to heart #2 (no stimulation), and got the same effect (vagus nerve was stimulated)
  • assumed that whatever was excreted from heart could be used to activate other heart (can stimulate nerve just by whatever was released)
  • this was the discovery of chemical transmission (the “vagus substance” was ACh)
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16
Q

GCAMP

A
  • Green fluorescent protein (GFP) + calcium binding protein calmodulin
  • calcium indicator for detecting neural activity, calcium binding causes a conformational change that excites GFP
  • Can look at many neurons simultaneously (as compared to patch-clamp)
  • Allows for in-vivo studying of neural circuits (can look at it live, as animal is doing the tasks)
  • But, is still just a proxy for neural activity
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17
Q

Synaptic transmission viewed at extremely high resolution

A
  • if you can look @ pics and see vesicles in presynaptic terminal, this is synaptic transmission
  • after TTX is added, vesicles don’t disappear, they are still there (there before stimulation, so ready to be released when stimulation does happen)
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18
Q

neuromuscular junction (NMJ)

A
  • an ideal model system to study synaptic transmission b/c of its simplicity (only dealing w/ a simple axon, w/ two or three terminals that innervate a muscle)
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19
Q

motor end plate

A
  • the rounded disk-shaped region of the muscle cell (the point of the NMJ)
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20
Q

schematic structure of the NMJ

A
  • acetylcholine-receptors on the muscle
  • junctional folds add surface area at muscle to pack in more nicotinic ACh receptors
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21
Q

8 steps of synaptic transmission at the NMJ

A
  1. APs propagate to the nerve terminals
  2. Voltage-gated Ca2+ channels open, increasing [Ca2+] in the terminals
  3. Exocytosis of synaptic vesicles, releasing ACh
  4. Ach diffuses across synaptic cleft
  5. ACh binds to postsynaptic nicotinic ACh receptors (nAChrs) and opens the receptors
  6. Na+ and K+ ions flow through nAChR channels, generating an inward end-plate current (EPC) into the postsynaptic cell and producing an end-plate potential (EPP)
  7. If the EPP is above the action potential threshold, one or more action potentials will be fired in the muscle fibers
  8. Acetylcholinesterase degrades the ACh and terminates signaling
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22
Q

curare

A

blocks ACh binding to ACh receptor (blocks muscle contraction, how paralysis happens)

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23
Q

α-bungarotoxin

A

blocks ACh binding to ACh receptor (the poison in snakes)

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24
Q

myasthenia gravis

A

autoimmune disease, immediate to mount strong muscle contraction, telltale sign is droopy eyelid

  • attacks body’s own ACh receptor (ACh receptors are still present, but at a much lower density, which prevents strong motor response from being mounted)
  • example of how deficits at the NMJ can cause disease
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25
Q

Postsynaptic responses at the NMJ

A

Bernard Katz, used frog muscle system and discovered spontaneous “minis” (mini EPPs): evoked spontaneous “mini” potentials and an evoked EPP, found that EPP was suprathreshold and elicit an AP in the postsynaptic muscle fiber

  • Found they were independent of nerve stimulation
  • Shape of minis were very analogous to EPP, hypothesized that putting these minis together might be what you’re seeing in EPP (we now know that each mini is a synaptic event)
  • We now know that we really need nerve stimulation, a lot at the same time, to lead to EPP
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26
Q

Muscle end plate potentials can lead to …

A

… muscle APs

  • EPPs can be isolated pharmacologically; if you sum a bunch of EPPs, you can reach AP threshold and get a spike in the muscle
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27
Q

End-plate potential (EPP) @ NMJ

A
  • Fast rise to peak in ~2-3 ms
  • Amplitude is largest near the endplates and decreased w/ distance - it’s a graded potential and propagates passively
  • EPP is produced by a brief surge of current at the endplate
  • EPP triggers APs when it’s large enough to reach the firing threshold
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28
Q

Postsynaptic responses @ NMJ

A

EPPs mimicked by direction application of ACh

  • Adding to TTX when stimulating the motor axon, no EPP
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29
Q

Directly pipetting ACh overcomes addition of TTX, revealing EPPs. Why?

A

b/c you can get to the result w/o having to go through the process (AP is meant to eventually release ACh into synaptic cleft through synaptic transmission)

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30
Q

End-plate current (EPC) @ NMJ

A

EPC produces the EPP

  • after performing experimental set-up, find that EPC elicited by single motor axon stimulation (induces ACh release) at Vm indicated
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31
Q

ACh causes inward current at negative membrane potentials, outward current at positive membrane potentials. Why?

A
  • Na+ goes inward, K+ goes outward
  • Turns out there’s a single channel, ACh receptor
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32
Q

ACh receptor

A

has reversal potential: potential at which sign of current changes, no longer net ionic driving force through channel

  • if ACh receptor was only permeable to one ion, its reversal potential would equal to equilibrium potential of that ion
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33
Q

EPP is produced by flow of _____ through the same ion channel

A

Na+ and K+

  • Na+ is inward, K+ is outward
  • Drives are equal and opposite, splits when we get very positive
  • @ very positive voltages, Na+ flows out of the cell b/c it is more positive than Na+’s equilibrium potential, so no drive to come into cell
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34
Q

Properties of the nAChR channel

A
  • Two extracellular binding sites for ACh on each receptor: ACh must bind to both sites to trigger channel opening
  • Non-selective cation channel; large pore does not discriminate between Na+ and K+ (reversal potential is ~0 mV)
  • Conducting both Na+ and K+ under physiological conditions, conduct mainly inward Na+ current
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35
Q

Calculating the end-plate current (Iepsp) through nAChR channel depends on four factors:

A

Iepsp = N x p open x 𝜸 x (Vm - Eepsp)

  • total number of end plate channels (N)
  • probability that a channel is open (p open)
  • conductance of each open channel (𝜸)
  • driving force on the ions (Vm - Eepsp)
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36
Q

AP generation at the NMJ

A
  • ACh released from presynaptic terminal, binds to receptor
  • Channel opens, Na+ inflow, K+ outflow
  • Depolarization (end-plate potential)
  • [Opening of voltage-gated Na+ channels
  • Na+ inflow
  • Depolarization (EPP) (return to opening of voltage-gated Na+ channels if AP doesn’t happen)
  • AP]
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37
Q

why is synaptic transmission in the brain and spinal cord more complex and harder to study than at the NMJ?

A
  • Hundreds of thousands of inputs even on single dendritic spine
  • Excitatory and inhibitory inputs
  • Many dif. types of neurotransmitters
  • Dif. types of receptors – ionotropic vs. metabotropic
  • Extensive spatial and temporal integration
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38
Q

synaptic potentials

A

post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs)

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39
Q

EPSPs _____ the likelihood of a postsynaptic AP

A

increase

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40
Q

IPSPs _____ the likelihood of a postsynaptic AP

A

decrease

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41
Q

In contrast to APs, EPSPs and IPSPs are …

A

… graded potentials that can summate

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42
Q

synaptic integration (summation)

A

Neurons sums inputs up

  • e.g. normally E1 and E2 enough to generate spike, but addition of I (an IPSP) can lower it so spike can’t be generated
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43
Q

How do you trigger EPSPs or IPSPs in most neurons?

A
  • Excitatory synapse: glutamate
  • Inhibitory synapse: GABA
  • In brain, glutamate is primary excitatory neurotransmitter and GABA is primary inhibitory neurotransmitter, but it’s more about receptors than about neurotransmitters
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44
Q

How is inhibition achieved?

A
  • Mechanism #1: membrane hyperpolarization
  • w/ inhibitory input (arrows), some APs are inhibited, resulting in a distinctive pattern of impulses
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45
Q

Inhibitory synapses are mediated by …

A

… ionotropic GABA and glycine receptor channels that are permeable to Cl-

  • blocking chloride ions blocks IPSPs
46
Q

Presynaptic inhibition occurs …

A

… throughout nervous system

  • e.g. chandelier inhibitory neurons wrapping around cortical excitatory neurons
47
Q

Steps of chemical synaptic transmission: transmitter release

A
  1. transmitter is synthesized and then stored in vesicles
  2. AP invades presynaptic terminal
  3. depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
  4. influx of Ca2+ through channels
  5. Ca2+ causes vesicles to fuse w/ presynaptic membrane
  6. transmitter is released into synaptic cleft via exocytosis
  7. transmitter binds to receptor molecules in postsynaptic membrane
  8. opening or closing of postsynaptic channels
  9. postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
  10. removal of neurotransmitter by glial uptake or enzymatic degradation
  11. retrieval of vesicular membrane from plasma membrane
48
Q

Calcium release (entry) is localized to …

A

… active zones @ presynaptic terminals, where there is the highest concentration of voltage-gated Ca2+ channels

49
Q

Calcium influx observed locally at …

A

… synapse; not much free calcium in the cell (bound by calcium buffers)

50
Q

Toxins that plug voltage sensitive calcium channels

A

snail conotoxin

  • drug name “Prialt”; used to treat chronic pain
51
Q

Synaptotagmin

A
  • a calcium sensor in synaptic transmission
  • entire gene knocked out, get dramatic response (response totally lost)
  • if you get rid of some single DNA sites for Ca2+ sensing, this reduced genes by 50%
  • other proteins @ synapse localize Ca2+ channels to make sure synaptotagmin is close enough to sense them
52
Q

Formation and dissociation of the SNARE complex drives fusion of the synaptic vesicles and plasma membranes

A
  • Vesicle released
  • Neurotransmitter needs to exocytose to fuse with membranes
  • Zippering, zipping up the vesicle
  • These proteins mediate the fusion, so that it becomes one continuous membrane and then the neurotransmitters are released
53
Q

Toxins that block vesicle release

A

Bacterial toxins (tetanus and botulinum) cleave SNARE proteins, preventing vesicle fusion at pre-synaptic terminals

54
Q

ionotropic: fast synaptic transmission

A
  • fast on (ms) and off (10s of ms)
  • mediated by ionotropic receptors
  • direct opening of ion channels (molecule binds and opens very fast)
  • EPSP or IPSP
  • can trigger APs
55
Q

metabotropic: slow synaptic transmission

A
  • slow synaptic transmission: seconds to minutes
  • mediated by metabotropic receptors
  • biochemical cascades; amplification
  • indirect opening or closing of ion channels (there’s binding to receptor that sets up series of cascade until you get the response)
  • EPSP or IPSP
  • usually no APs are triggered
  • modulation of neuronal excitability
56
Q

Many types of ionotropic receptors

A

For each receptor, there are genes that contribute to receptor

  • mix/match the subunits that come together
  • various of combination of genes
57
Q

what determines fast vs. slow synaptic transmission?

A

the RECEPTOR, not the transmitter

58
Q

Ionotropic glutamate receptor

A
  • AMPA Ligand gated channel: glutamate binds the receptor, opens it, ion influx
  • NMDA: multiple binding sites
59
Q

Metabotropic glutamate receptor

A

Has slow transmission, in cascade manner

60
Q

Properties of AMPA receptors

A
  • Non-selective cation channel
  • Permeable to Na+ and K+
  • Conduct inward Na+ current at the resting membrane potential
  • Fast opening and desensitization
  • Block by CNQX
  • Adding glutamate and increasing concentration has more inward sodium current
61
Q

Properties of NMDA receptors

A
  • like AMPA, is also non-selective (permeable to both Na+ and K+)

special properties:

  • Permeable to Ca2+
  • Voltage-dependent block by extracellular Mg2+ (cells at resting membrane potential, there’s extracellular Mg2+ present, this Mg2+ blocks the pore so that it blocks transduction; need depolarization to remove Mg2+ to get transduction; need Glutamate, ligand binding, and depolarization to remove Mg2+)
  • Requires glycine as a cofactor
  • Block by AP5
62
Q

If NMDA receptors can’t be opened until sufficient depolarization, how does Na+ enter in the first place upon glutamate release from presynaptic terminals?

A

Coexpressed alongside AMPA receptor

  • always find AMPA receptor alongside NMDA receptor
  • AMPA is the principal glutamate receptor, NMDA is like a backup.
63
Q

Synaptic responses of AMPA and NMDA receptors

A
  • Weakly active synapse (some depolarization, some sodium influx, but weakly activated, not enough to activate NMDA receptor; current is mainly driven by AMPA)
  • Strongly active synapse (enough coming through AMPA, enough sodium to depolarize the neuron that removes the Mg2+ on NMDA receptor and you get an influx through NMDA receptor)
64
Q

What’s the purpose of NMDA receptors anyways when you have AMPA receptors?

A

To amplify it further

  • Ca2+; NMDA receptor allows Ca2+, which the AMPA doesn’t
  • Ca2+ is very important signaling molecule that sets off cascade
65
Q

I/V relationship of AMPA and NMDA receptors

A
  • AMPA - this looks similar to nAChR: no voltage dependence, completely ligand dependence (linear relationship between I/V)
  • NMDA - it has voltage dependence; will open when depolarized; if we don’t have Mg, then it looks just like AMPA (non-linear relationship between I/V at negative voltages)
66
Q

GPCRs - a type of metabotropic receptor

A
  • Longer-lasting effects: minutes, hours, days or longer
  • At least 800 genes in humans, 1300 in mice, 700 in zebrafish
  • Almost 1% of the entire genome!
  • About 50% of all drugs target GPCRs
  • Important part of sensory systems like olfaction, taste, and vision (opsin is a GPCR)
  • Found in all animals, fungi, and some protists, but not plants
  • have 7 membrane-spanning domains (receptor binds to complex of G-proteins)
67
Q

Activation of G protein coupled receptors

A

Binding of ligand causes GDP to be replaced by GTP on the inactive G protein trimer, which then dissociates into active α and β𝜸 subunits

  • Receptor, associate with trimeric complex called G proteins; GDP binds to this; when agonist binds and activates, GTP is transferred in, and you lose GDP; in this state, alpha beta gamma subunit dissociate to act of different target proteins
68
Q

Are synapses static or fluid during important behavioral states?

A

studied the circuit in the hypothalamus using a female mice model

  • there are certain windows when female mice are sexually active b/c of AVPV and PVL neurons

Two sets of experiments:

  • synaptic terminals in fluorescent proteins: basal unprimed and primed state (state of estrus)
  • dif. expression pattern: female mice ONLY mate in state of estrus
  • used Syp:mCherry as a fluorescent marker b/c Syp:mCherry protein that localizes to synapse; inject fluorescent marker into neuron and it will only label the synaptic terminal
  • there are more synapses during estrus state, changes activity of AVPV neurons –> getting more inputs
  • during estrus state, there’s more synapses going to AVPV neurons; when they are not in this state, synapses go back (depending on the state that animal is in, they can be modified) (estrus get to the brain (neurons have estrus receptor) –> they sense high estrus state and grow more synapses. When not in that states, the synapses go back)
  • you can grow or release synapses: synapses are dynamic even after development
69
Q

Examples of slow synaptic transmission

A
  • Sympathetic nerve stimulation speeds up heart beat (activating sympathetic nerve speeds up the pacemaker potential)
  • Parasympathetic (vagus) nerve stimulation slows down heart beat (heart has its own AP called pacemaker potential; when you stimulate vagus nerve, these potentials slow down)
70
Q

Acetylcholine hyperpolarizes heart cells (rabbits)

A

When you add ACh to a myocyte (heart cell), you see slow voltage in the heart; but if you look at current, adding ACh, and current in heart cell, we see robust outward current (looks like outward potassium current, potassium leaves and hyperpolarizes neuron)

71
Q

Metabotropic acetylcholine receptors

A

slows down heart rate

  • ACh binds muscarinic ACh receptor, activates G-proteins
  • G(beta gamma) when liberated, go to directly activate K+ channel, leading towards K+ efflux from heart cell, leading to hyperpolarization, that leads to slow down heart rate
72
Q

Intracellular application of Gβ𝜸 mimics ACh action at the extracellular surface

A
  • Current by adding ACh
  • Get the same thing when you add gamma beta, as well
  • These are still outward currents but inverted in the graph because the way they measured it
73
Q

Metabotropic beta-adrenergic receptors

A

speed up heart rate

  • Norepinephrine binds, basal complex, and activated complex
  • Adenylyl cyclase converts ATP to cAMP
  • cAMP activates kinase (pKA)
  • pKA is activated and activates the voltage-gated calcium channel
  • once calcium channel is activated, you further depolarize the heart, speeding up the heart rate
73
Q

fast EPSP is produced by activation of …

A

… ionotropic nicotinic ACh receptors

74
Q

slow EPSP is produced by activation of …

A

… metabotropic muscarinic ACh receptors

  • this receptor stimulates PLC to hydrolyze PIP2, yielding IP3 and DAG
  • the decrease in PIP2 causes the closure of the M-type delayed-rectifier K+ channel
75
Q

To be considered a neurotransmitter, a molecule must satisfy these four criteria:

A
  1. It is synthesized in the presynaptic neuron
  2. It is present in the presynaptic terminal and is released in amounts sufficient to exert a defined action on the postsynaptic neuron or effector organ
  3. When administered exogenously in reasonable concentrations, it mimics the action of the endogenous transmitter (e.g. it activates the same ion channels or second messenger pathway in the postsynaptic cell)
  4. A specific mechanism usually (but not always) exists for removing the substance from the synaptic cleft
76
Q

Commonly used neurotransmitters

A

acetylcholine, glutamate, GABA, glycine, serotonin (5-HT), dopamine, norepinephrine, histamine, neuropeptides

77
Q

Neuropeptides require _____ for release and can act over _____

A

strong stimulation of the neuron, large distances

  • Neuropeptides tend to be more packed and in dense core vesicles
  • They act over long distances (as long as the neuron has the receptor for neuropeptide, they can be opposite ends of the brain); as long as peptide isn’t broken down, it can still act
  • They are not always released from terminals, can be released from soma or dendrites
78
Q

Neuromodulation by neuropeptides

A

One postsynaptic neuron receives input from three different neurons:

  • Neuron 1: glutamatergic, activate it, we get fast EPSP
  • Neuron 2: activate it, slow EPSP
  • Neuron 3: no EPSP

Combining actions of 1, 2, 3, we see neuromodulation of fast EPSP

  • secretion of neuropeptides can modulate neural activity
79
Q

Studying neural activation in vivo during behavior: e.g. dopamine release

A

Visualize neuropeptides in real time in behaving animals

  • e.g. we want to see dopamine dynamics: as the animal is doing something rewarding, we want to keep dopamine release in real time
  • Take D2R (dopamine receptor) that binds dopamine; add GFP to this receptor that doesn’t interfere with dopamine binding; only see fluorescence when dopamine binds
  • Dopamine sensor: stronger color means activation; you give mice water and at baseline (naive state) you get strong dopamine release measured by sensor
  • Trained (tone followed by water): w/ the tone of water, see dopamine release
80
Q

synaptic plasticity

A

the ability to change the efficacy of synaptic transmission

  • neural activity generated by an experience that modifies brain function via modifying synaptic transmission
  • Divided according to timescales: short-term lasts milliseconds to minutes, long-term can last for hours to minutes
81
Q

Paired-pulse (pulsing cell, then pairing it) synaptic facilitation

A

Facilitating synapse: successive APs produce larger post-synaptic responses

82
Q

Paired-pulse (pulsing cell, then pairing it) synaptic depression

A

Depressing synapse: successive APs produce smaller post-synaptic responses

83
Q

RRP (release-ready pool)

A

molecules that are already ready and primed

  • also have larger recycling pool (vesicles reuptaken by neuron) and reserve pool of vesicles, will be constantly replaced when needed
84
Q

Paired-pulse depression typically results from …

A

… a transient depletion of the release-ready pool (RRP) of vesicles docked @ presynaptic terminal

85
Q

Paired-pulse facilitation results from …

A

residual calcium left over from the invasion of the first AP, contributing to additional release during the 2nd stimulation

86
Q

Released probability (high or low) at a given synapse can dictate …

A

… whether you observe facilitation or depression

87
Q

Aplysia californica as a simple system to unlock the synaptic basis of learning and memory

A

Experimental setup w/ sea snail b/c small nervous system (20,000 neurons) and simple behaviors

  • Give Aplysia electric shocks, will teach the snail that “the world is a dangerous place,” trigger reflex of gill and siphon: if gill and siphon remain contracted, that will show that it has learned to be on guard (Aplysia that hasn’t been taught will still contract, but will un-contract quickly)
  • Form a mini brain, see that synapse between sensory and motor neuron becomes stronger: administer shocks over time (long-term memory), neurons will physically change structure (more connections will be made) –> shows that learning and memory are happening, and how it happens
88
Q

Short-term habituation of the gill-withdrawal reflex

A

short-term, involves a decrease in presynaptic transmitter release

  • in Aplysia, decrease in EPSP leads to not as robust gill-withdrawal response
  • brain learns to ignore neutral stimulus; opposite is true for painful stimuli (detected by pain-sensing neurons)
89
Q

Short-term sensitization of the gill-withdrawal reflex

A

Pain-sensing neurons able to enhance response (be more robust)

  • enhance EPSP in motor neuron (post-synaptic neuron), leads to bigger and longer gill-withdrawal reflex
90
Q

Presynaptic facilitation of the gill-withdrawal reflex involves two molecular pathways

A

Both metabotropic receptors, dif. downstream cascades

  • Serotonin is major transmitter, activates metabotropic serotonin receptors (in between sensory neuron (pain neuron) and facilitating interneuron)
  • stronger calcium influx = stronger activation
  • PKC promotes moving from reserve pool to ready release pool
  • everything caused by stronger synaptic communication
91
Q

Classic conditioning of the gill-withdrawal reflex, “unpairing the two stimuli”

A
  • If unpaired, won’t see sensitization, potentiation, etc.
  • If classical conditioning present paired pathway happens, pair stimulation occurs and learning and memory now happens
92
Q

Long-term synaptic plasticity

A

Activity-dependent, long-lasting modifications of synaptic strength that modify future behavior

93
Q

Long-term sensitization involves …

A

… synaptic facilitation and the growth of new synaptic connections

Requires gene expression, new protein synthesis, and formation of new synapses

  • Genes work in concert, some work to facilitate long-term synaptic growth

w/ long-term sensitization, can grow new synapses (b/c neurons become more sensitive to stimuli)

Five spaced trainings of serotonin facilitating neurons (or repeated application of serotonin) during a one hour period can produce changes for 1 day; longer training can produce sensitization that last weeks

94
Q

Long-term habituation can cause the …

A

… retraction of synapses

95
Q

Long-term potentiation (LTP) in hippocampus

A

patient HM (Henry Molaison) used to show this

  • hippocampus is indispensable for learning and memory (needed to turn short-term memories into long-term memories), most studied part of brain
  • HM suffered from seizures that affected medial lobe, removed both hippocampi (hippocampus on each side); seizures cured, but greatly affected memory
  • HM’s cognitive abilities spared, still remembered things that were already committed to long-term memory, just couldn’t make new long-term memories
96
Q

Information flow in hippocampus

A

Perforant pathway from entorhinal cortex: 2 dif. pathways, direct and trisynaptic

  • Entorhinal cortex major inputs into hippocampus
  • trisynaptic: entorhinal cortex major inputs –> granule cell (in dentate region) –> mossy fiber pathway –> CA3 –> Schaffer collateral pathway –> CA1
  • direct: straight to CA1
  • CA1 are major output neurons of hippocampus
97
Q

Can read activity in hippocampus to determine where mouse was in maze

A

Neurons fire @ particular spots in maze, forming a mental roadmap

98
Q

Chickadee as a model for neuroscience to study episodic memories in the hippocampus

A

Bird has catching behavior, bird can hide the food after gathering from a feeder and remember where it is weeks, months later

99
Q

LTP can last >1 year in animals

A

Tetanus of 400 Hz trains of stimulation in rat hippocampus, this high frequency stimulation can change synapse for up to a year

100
Q

How to prove that NMDA receptors are essential for LTP?

A

Block receptors w/ antagonist, see if LTP still happens

101
Q

How to prove that postsynaptic Ca2+ increase is essential for LTP?

A

Use Ca2+ sponge, see if LTP still increases

102
Q

How to block LTP:

A
  • Block NMDA receptors w/ APV (AP5)
  • Block postsynaptic calcium w/ EGTA
103
Q

Molecular mechanisms leading to the expression of LTP:

A
  • Increased activity of existing AMPARs (AMPA receptors)
  • Diffusion of extrasynaptic AMPARs to synapse
  • Insertion of additional AMPARs
  • Conversion of silent synapses to active synapses
  • Everything is downstream of Ca2+
104
Q

Silent synapses contain only …

A

… NMDA receptors

  • NMDA only activated w/ significant depolarization from membrane (need very strong depolarization for current to flow, otherwise will stay plugged w/ Mg2+)
105
Q

How can NMDA be activated during LTP (Ca2+ flow through channel) w/o AMPA receptors?

A
  • Experimentally, alter Mg2+ concentration, just depolarize that specific point until Mg2+ removed
  • When occurring naturally, have multiple dendrites attached to this axon, those synapses have AMPA, get enough depolarization from neighboring input
106
Q

Molecular mechanisms of long-lasting synaptic changes

A

Need gene expression to get growth of new synapses after LTP addition

107
Q

An issue w/ LTP:

A

LTP is not natural: is produced through experimental stimulation

  • Phenomenon downstream is interesting, but it doesn’t really happen in nature
  • Experiments are useful, but if so not natural, run the risk of not being able to interpret it
108
Q

Long-term depression (LTD) in hippocampus

A

Synapse becomes weaker over time, done through low frequency stimulation

109
Q

Molecular mechanism of LTD:

A
  • NMDARs are involved
  • Produced by slow rise in postsynaptic Ca2+
  • Protein phosphatases are involved
  • APARs are endocytosed

Neurobio I (4 decks)

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