5. Neurophysiology II Flashcards
Synaptic transmission
How to convert an electrical signal into a chemical signal and back again.
- Presynaptic region
- ____ to ____
- ____ triggered transmitter
release - Synaptic cleft
- diffusion of ____ - Postsynaptic region
- ____ to ____
- ____-linked potential changes
electrical
chemical
voltage
neurotransmitters
chemical
electrical
receptor
Presynaptic region in axon terminal
Chemical storage of neurotransmitter in synaptic vesicles.
Presynaptic potential and thus ion channels regulate neurotransmitter release
Voltage-gated channels conduct AP’s down the axon to the terminal (1).
Depolarization gates open voltage- gated ____ channels to permit entry of Ca+2 into presynaptic terminal during an AP (2).
This influx of Ca+2 is the trigger for synaptic vesicles already ____ (3) to fuse with the membrane (4) and release ____ into the synaptic cleft (5).
Ca++
docked
NT
Presynaptic region: vesicles docked and ready to go
First line of synaptic vesicles in position to release when signal of Ca2+ elevation received
Voltage gated Ca2+ channels ____ close by to make process more accurate and rapid - 200 μs
Ca2+ rises from 100 nM to 100 μM – ____x
physically
1000
Presynaptic region: vesicles in terminal bouton
* \_\_\_\_ provides energy to load NT into vesicles * \_\_\_\_-demanding region of the cell
mitochondria
energy
Presynaptic region: synaptic vesicle
____ helps dock, and binds increasing ____ to initiate release
• Load vesicles with NT ○ \_\_\_\_: proton pump to pump + charge protons (acts as counter ion to negative charges of glutamate) • Proteins necessary for targeting vesicles at release ○ \_\_\_\_ ○ \_\_\_\_ - key protein needed to move vessels into right position • Proteins involved with docking of vessels ○ \_\_\_\_ ○ \_\_\_\_ • Synaptotagmin: where \_\_\_\_ binds ○ Reason why we have rapid entry of Ca++
synaptotagmin
Ca++
glutamate
calmodulin-dependent kinase II
synapsin
synaptophysin
synaptobrevin
calcium
Presynaptic region: targeting, docking and fusion of synaptic vesicle
Also “____” release
• \_\_\_\_: anchor vesicle • \_\_\_\_: calcium binding unit C2A and C2B • When vesicles are waiting for AP in absence of Ca++ ○ Loosely \_\_\_\_ and primed • When Ca++ enters via channels ○ \_\_\_\_ twisting of docking proteins ○ \_\_\_\_ of synaptoatotegmin start to move - putting their elbows through double membrane ○ Takes a lot of \_\_\_\_ to break vesicular and PM at synapse • Fusion of vesicular and PM takes a lot of energy ○ Mediated through \_\_\_\_ changes of protein • Expansion of pore ○ NT released • Kiss and run ○ A little semi-opening for a little \_\_\_\_ to release and it closes up again ○ \_\_\_\_ emptying of synaptic vesicle on plasma membrane • Membrane turnover on synaptic membrane
kiss and run
synaptobrevin synaptotegmin tethered tighter C2 energy allosteric NT incomplete
Transport of synaptic vesicle
Is ____ until after docking with SNARE complex, my boy!
____ leads synaptotagmin to insert in the membrane causing a mechanical
trigger that opens the pore.
____ isoforms cleave SNAP 25, syntaxin or synaptobrevin, thus preventing neurotransmitter release
t-SNAREs are the target snares on the ____.
v-SNAREs are on the ____.
[points to tethering complex] You can see it is tethered and the tethering complex brings it close and holds it in position. The SNARE complex begins to loosely form and is ____ until fusion. This happens so neurotransmitter can be released immediately
when calcium arrives.
Once calcium comes in, that fusion occurs really quickly, and the neurotransmitter is released.
[points to bottom diagram] This is the best picture showing how ____ is
primed and interacts with the v and t-SNARES. Once that calcium comes in, you can really see the Synaptotagmin starting to fuse.
reversible
Ca++
botox
plasma membrane
vesicle
reversible
synaptotagmin
Botox soldiers with chainsaws
____ used for injection, exhibits an LD50 of 40-56 ng when injected iv, one of most powerful toxins known
• Cleave \_\_\_\_ machinery ○ B, D, F, and G cleave \_\_\_\_ ○ A and E cleave \_\_\_\_ and \_\_\_\_ • Impede with botox - prevent synaptic release, prevents vesicular fusion • Injecting botox into regions with \_\_\_\_ interactions - preventing the movement of those muscles ○ No laughter lines, wrinkles because you prevent the NM transmission
snare synaptobrevin snap-25 syntaxin neuromuscular
Synaptic cleft: the gap between two neurons or between a neuron and its effector organ
- Neurotransmitters diffuse across the synaptic cleft to the postsynaptic membrane
- Neurotransmitter is either taken up into the ____ terminal or inactivated by ____ located in the cleft.
____ volume: 200-300 angstroms small enough for fast diffusion
Filled with matrix, enzymes, receptors, other proteins
• \_\_\_\_ - feedback mechanisms, can stop or induce interactions
presynaptic
enzymes
small
autoreceptors
How does the neurotransmitter signal stop?
- ____ degradation. (e.g. acetylcholinesterase)
- Messages can be transported back into the ____ terminal for recycling.
- ____ of the message away from the site of the post-synaptic receptors.
Important to limit concentration of transmitter both ____ and ____ to ensure specific signaling
enzyme
presynaptic
diffusion
spatially
temporally
Increasing 5-HT (serotonin) in synaptic cleft by blocking uptake
• Inhibit \_\_\_\_ uptake, thereby resulting in a build up of serotonin in the cleft
presynaptic
Postsynaptic region
• Receptors for the neurotransmitter
– ionotropic vs metabatropic:
type dictates ____
• Neurotransmitter binding causes change in the membrane potential
– the particular ion flowing through the channel will determine whether the effect is ____ or ____ depending upon its Nernst potential
• Ionotropic channels ○ Ligand gated ion channels • Metabotropic channels ○ GPCR • Choice between is going to affect the speed of the response • \_\_\_\_ can activated both in same synapse, but lead to different outcomes • NT targets and opens ionotropic: ○ If Na-selective: lets more Na+, thereby depolarize - \_\_\_\_ ○ If K-selective (flows out), or Cl- (flows in): hyperpolarize - \_\_\_\_ • NT targets metabotropic: ○ Essentially an enzyme, and acts as a GPCR ○ Activates \_\_\_\_ pathway § Alters state of \_\_\_\_ channels - can open them § However, they can also \_\_\_\_ the channels (opposite scenario) ○ Change \_\_\_\_ transcription, learning signals
timing
excitatory
inhibitory
glutamate
EPSP
IPSP
second messenger
ion (ionotropic)
close
gene
Postsynaptic region: Ionotropic receptors
- Ionotropic receptors are ____ gated channels
- Distinct agonist binding and pore regions of receptor – contain all ____ aspects of normal ion channels
- Very ____ – low msec
•Examples:
NMDA – binds ____,
____ permeable depolarization- excitatory
GABA A – binds ____, Cl- permeable, ____ entry hyperpolarization- inhibitory
____ – dental pain
• Need NT binding site ○ Acetylcholine has two binding sites • Binding leads to allosteric changes, opening the pore and allows ions to travel in direction of electrochemical gradient • P2X for \_\_\_\_ important in dental pain
ligand
exciting
fast
glutamate
Na+/Ca+
GABA
Cl-
P2X
ATP
Ionotropic P2X receptors: key mediators of dental pain
- Identify dental pulp nerves by injecting with fluorescent dye, allowing transport to soma in ____ before removing
- Extracellular ____ applied to cell initiates action potentials, adapting. Pharmacologically and immunohistochemically identified as P2X2/P2X3 hybrid channel
- Think ATP released from ____ dental tissue
- Recorded from patch clamp - you add ATP - you see AP coming from the neuron
- Occur in a ____, two ____
trigeminal ganglion ATP inflamed trimer domains
Postsynaptic region: Metabotropic receptors
Receptor initiates multiple steps before changing membrane potential
Links to depolarization or hyperpolarization more ____ because more steps
Much ____ than ionotropic receptors but can have longer ____ effects
Important for ____ signal
G-protein coupled, tyrosine kinases etc
• G-proteins ○ Requires hydrolysis of \_\_\_\_ to GDP following allosteric changes in receptor • Usually span \_\_\_\_ membranes • Alpha, beta and gamma subunits ○ \_\_\_\_: PLC, release of Ca+ from ER, and can activate phospho on membrane ○ \_\_\_\_: stimulatory - increases activity of adenylate cyclase and increase cAMP ○ \_\_\_\_: inhibitory - reduce cxn of cAMP
variable slower modulating amplifying GTP 7 Aq Gs Gi
Postsynaptic region: Metabotropic receptors
- Binding of neurotransmitter initiates allosteric changes in receptor
- G protein activated – GDP replaced by GTP, ____ dissociates from Gβγ
- Much more GTP than GDP so initially supply no problem but can be after continued stimulation
- Gα and/or Gβγ activate additional enzymes – in this case Gα stimulates ____ to produce cAMP• GTP to GDP, release of P, transferred to GDP, activating ____
• Binds adenylate cyclase, turning ATP to cAMP
• More GTP to GDP usually within cell
○ Not the ____ step
• Beta, gamma, are very ____ on their own
Galpha
adenylate cyclase
Galpha
rate-limiting
active
Postsynaptic region: Metabotropic receptors and the release of intracellular Ca2+
- Stimulated receptor activates ____
- Gqα activates ____
- PLC activates ____
- IP3 binds to membrane on ____
- ____ released from ER
- Mediates many actions• ____ are the second biggest source of Ca++ in cell
○ ____ leading to release of signal
Gqalpha PLC IP3 ER Ca++
lysosome
TLR3
Adrenaline (epinephrine) has multiple responses depending upon what GPCR it stimulates
* Different receptors depending on g-proteins coupled to * Alpha1 - Gq - PLC - IP3 - release of \_\_\_\_ from ER - contraction of \_\_\_\_ muscle * Alph2 - Gi - \_\_\_\_ adnylyl cyclase - reduction o of Camp * Beta - Gs - increase \_\_\_\_ - increased by cAMP (blocked by \_\_\_\_)
Ca++ smooth inhibits adenylate cyclase beta blockers
Proposed purinergic signaling pathways underlying the cellular responses associated with P2 receptor activation in various areas of the tooth
Be aware that a single neurotransmitter (ATP)
Can initiate ____ in a single organ.
Many of these linked to ____
• P2Y6 (metabotropic channel (leads to transcriptional regulation of cytokine \_\_\_\_) • P2X7 - cytokine \_\_\_\_ • Mechanical stress - P2Y - \_\_\_\_ - second messengers - influence inflammation • Nerve cells - \_\_\_\_ stimulation P2X2A3 - pain • Stimulate ATP mediating via \_\_\_\_, leads to activation of inflammasome \_\_\_\_ - used to trigger maturation and release of \_\_\_\_ (major inflammatory cytokine around) • Occurs in both \_\_\_\_ and \_\_\_\_ cells • Drugs based on \_\_\_\_ to stop pain ○ Opioid crisis will force development of more analgesic pathways
multiple responses
inflammation
IL6 IL8 PKA ATP connexin NLRP3 IL1beta neural non-neural purines
Postsynaptic density: molecular scaffolding to keep receptors in place, mediate effects of stimulation
- PSD across from docked synaptic vessicles
- ____ and ____ elements
- Clusters ____ and receptors
- Important in ____ potentiation - ____ – ____- transcription• When PS receptors stimulated they’re support in PS density
• NMDA important in learning
• Organization in PSM is critical in consequences of NT activation
○ ____
○ Very tightly regulated underneath the ____
cytoskeletal regulatory ion channels long-term NMDAR CAMKII
rafts
membrane
PSD-95 marks synapse location on dendrites
____ –
gets synaptic vesicles to pre- synaptic release site
PSD-95
SYNAPSE
* Protein that indicates where PSD are located * Neuron in culture and stain in green (PSD-95) * Synapsin in yellow * Many sites where \_\_\_\_ and \_\_\_\_ are together (\_\_\_\_and \_\_\_\_)
synapsin synapsin PSD presynaptically postsynaptically
Key steps in synaptic transmission
- An AP travels down axon and depolarizes presynaptic terminal.
- ____ channels open in response to the depolarization.
- Ca+2 enters the synaptic terminal through Ca+2 channels.
- Increased [Ca+2] activates neurotransmitter release from ____.
Ca++
vesicles
Key steps in synaptic transmission
5. Neurotransmitter in the synaptic cleft either:
a) binds to ____ on the postsynaptic membrane
b) is ____ or ____ away or is recycled before it binds to a receptor
6. The post-synaptic membrane potential changes:
a) Depolarizes if excitatory
b) Hyperpolarizes if
inhibitory
receptors
degraded
diffused
Many drugs of interest interfere with synaptic transmission
Drugs can be used to enhance or impede many steps in synaptic process
• Drugs that have been developed target neurotransmission - multiple ways to increase or decrease the transmission by manipulating the process • Agonistic: ○ Increase synthesis of \_\_\_\_ (precursor) ○ Destroy degrading \_\_\_\_ ○ Inhibit the negative feedback of autoreceptors ○ Stop the \_\_\_\_, increasing cxn in cleft • Antagonistic ○ Increase molecules that break down NT ○ Break down molecules that synthesize ○ Block \_\_\_\_ receptors
NT
enzymes
reuptake
postsynaptic
Electrical synapses
- All synapses discussed until now chemical synapses, message spread between neurons ____ nm apart by chemicals released into synaptic cleft
- Also electrical synapses – cells ____ connected through ____, ____ nm apart. ____, but no gain. Usually ____.• Amount of ____ is greatly reduced
○ Bidirectional via gap junctions
• Made up of ____ that make up a ____
20-30 mechanically gap junctions 3 faster bidirectional
processing
connexins
connexon
Gap junctions
- Gap junctions important in ____ or ____ communication
- In addition to electrical signal, allow passage of compounds
glial-glial glial-neuronal 1000 nucleotides cAMP block
Neuronal transmission – how to code in the post synaptic membrane A. Generation of an EPSP or IPSP B. Spontaneous release of neurotransmitter vesicle packets C. Generation of an AP D. Pre-synaptic inhibition E. Spatial summation F. Facilitation G. Temporal summation H. Adaptation I. Synaptic efficacy J. Synaptic fatigue
YAY
Neuronal transmission
A. Generation of an EPSP or IPSP
Binding of neurotransmitter to receptor opens channels and changes membrane potential
In CNS, ____ synaptic event usually not enough for an action potential alone – only changes 0.5- 1 mV
IPSP
- Inhibitory post synaptic potential
- Receptor lets in Cl- (or out K+) to hyperpolarize membrane
EPSP
-Excitatory post synaptic potential -Receptor lets in Na+ or Ca2+ to depolarize membrane
* Relates binding of NT to \_\_\_\_ that either depolarizes or hyperpolarizes the membrane * Depolarize: Na or Ca inwards * Inhibitory: Cl in or K out
single
ionotropic
Neuronal transmission B. MEPSPs
While release is usually triggered, can occur ____:
miniature excitatory post- synaptic potential MEPSP (or MEPP in NMJ) show quantal release with all vesicles the same ____. Show response to the amount of transmitter in a single vesicle.
Warning: Many aspects of quantal release discovered with NMJ with all-or-none signaling Numbers of quanta per AP, amplitude of MESPS can be much less in ____ so need more individual terminals to converge.
• Release of Ach leads to depolarization of \_\_\_\_ mV • Relating to quantal releases ○ Vesicles have same amount of \_\_\_\_ within them • Figured out using NMJ ○ All-or-none signaling - hits threshold in order to contract ○ Don't apply for \_\_\_\_ • \_\_\_\_ release, more variation in the amount • Require many more vesicles to be released in order to lead to AP
spontaneously
size
CNS
1
material
CNS
kiss-and-run
Neuronal transmission C. Generation of an AP
In CNS, single synaptic event usually not enough for an action potential alone
____ mV depolarization necessary to reach AP threshold in post synaptic cell - 0.5-1 mV each synaptic event
Requires many ____ to release transmitter and sum together
Effectiveness of summing dependent on ____ and ____ release occurs
• Require multiple synaptic release events to reach AP ○ Depolarize by 20 mV to reach threshold ○ 0.5-1 mV per event
10-20
terminals
where
when
Neuronal transmission D. Presynaptic inhibition
Inhibitory synapses can contact the presynaptic terminals thereby making it more difficult to excite the terminal and release neurotransmitter.
____ or ____ are the usual inhibitory neurotransmitters. Stimulation of these inhibitory pathways may have relatively ____ effects on the presynaptic membrane.
____ inhibition can also limit transmission of pain signals
• Inhibit the presynaptic terminal prevent release of NT • GABA/glycine - inhibitory NT - influx of Cl • Modulation of pain ○ \_\_\_\_ - transmission of pain from first to second order neuron ○ \_\_\_\_ - reduces the release of substance P - inhibit the transmission of the pain signal
GABA
glycine
long-term
presynaptic
substance P
enkephalin
Inhibition or excitation depends on ion channels opened in postsynaptic cell
• \_\_\_\_ spreads to spike initiating - AP
depolarization
Neuronal transmission
E. Spatial summation/ G. Temporal summation
Temporal: Each postsynaptic depolarization lasts ____ msec.
Arrival of another stimulus from same ____ neuron in this interval
adds to the depolarization, may reach threshold
Spatial: Stimuli from +1 presynaptic neurons in close ____ sum together
If one input is excitatory and the other inhibitory, ____ each other out
15
presynaptic
proximity
cancel
Neuronal transmission
E. Spatial summation/ G. Temporal summation
• Graded EPSPs and IPSPs come in through ____, but “Go/No Go decision” on whether to fire made by voltage gated ____ channels at ____.
dendrites
Na+
axon hillock
Neuronal transmission
E. Spatial summation/ G. Temporal summation
Remember that because graded potentials reduce amplitude with ____, proximity to ____ can alter influence.
Here we begin to see how the distance can affect this. In the end, the further you are away from the axon initiating segment, the
____ influence you really will have on the membrane potential.
Excitatory synapses can depolarize the dendrites quite a lot. But,
it is a ____ transmission. So it will fade with distance.
Inhibitory input closer to the ____
(spike initiating zone) is going to have a bigger affect.
So you can modulate the impact that this release has
by changing where it is and by changing whether or
not you have the synapse getting closer to where you
decide on that action potential. Because that
dissipation of the signal will reduce the impact of the
signals that come from farther away.
distance soma less graded axon initiating segment
Neuronal transmission F. Facilitation
- For a limited time after the arrival of an action potential, the post synaptic nerve is ____: a given input will produce a larger post synaptic response
- Facilitation depends on spike frequency – ____ msec
- Facilitation is due to increases in local ____ levels in presynaptic terminal, more synaptic vesicles are released if second action potential arrives quickly, larger post synaptic response
This will give you an enhanced post-synaptic response due to the ____ presence of calcium in the pre-synaptic cleft.
facilitated
10-20
Ca++
residual
Neuronal transmission H. Adaptation
Change in ____ over time – code signal in ____ of action potentials
Frequently seen in ____ receptors
In rapidly adapting neuron, ____are signaled
In slowly adapting neuron, response is more ____
(Remember, amplitude of action potential is all or none, but ____ is what changes)
Slowly adapting: Sensation more ____ at start but present throughout stimuli
* Changes in \_\_\_\_ or \_\_\_\_ are effective at detecting change * AP are all the same \_\_\_\_, but the frequency determines the coding
responsiveness frequency sensory on and off sustained or tonic
frequency
acute
vision
movement
magnitude
Neuronal transmission J. Synaptic efficacy
Synaptic efficacy: efficiency of ____ between different neurons
Changes in efficacy underlie ____and memory
Efficacy altered by: ____ (alkalosis increases ____)
hypoxia (decreases ____)
anesthetics (usually ____ threshold and thus
decrease ____)
How big a change in the post synaptic membrane potential will release from a given synapse make
– gain in the system
In ____, all or none but in ____, more subtle
* How big a change in the PSM will release from a given synapse will make * Not an all-or-none response… * Stimulating presynaptic neurons… you can determine which one is \_\_\_\_ than the other * Can quantify how far from \_\_\_\_ by seeing if it can form an AP…
coupling learning pH excitablity excitability increase excitability
NMJ
CNS
stronger
soma
Neuronal transmission J. Synaptic fatigue
Most neurons store enough neurotransmitter for ____ synaptic discharges.
Over-excitation can lead to a depletion of ____ resulting in a loss of ____
Fatigue sources:
loss of ____
loss of ____
10,000 NT excitability neurotransmitters ionic gradients
What are these neurotransmitters whose binding enables synaptic transmission?
• Depends on the \_\_\_\_ of fit… How \_\_\_\_ is the drug in the active site
tightness
stable
Neurotransmitter requirements
- The neurotransmitter must be synthesized in the ____ and stored in the ____
- The neurotransmitter must be released from the ____ upon depolarization
- Application of the neurotransmitter ____ (with a pipette) must generate the same response as stimulating the ____
neuron nerve terminal terminal exogenously presynaptic nerve
TABLE OF NEUROTRANSMITTERS
LOOK AT THIS!
YA
Classes of Neurotransmitters
- ____
- Amino acids
- ____
- Opioid
- ____
biogenic amines
neuropeptides
other
Classes of Neurotransmitters
- Biogenic amines:
a. ____:
Dopamine (DA) - ____, motivation
Epinephrine (Epi) (adrenaline) – ____ Norepinephrine (NE) – ____, attention
b. ____: Acetylcholine (ACh) ____- muscle contraction
CNS - ____ and ____ term memory
c. ____:
Serotonin (5HT) - ____, mood
Histamine - sleep, ____ response, immune respons
catecholamines
movement
fight or flight
stress
cholinergic
peripheral
learning
short
indolamine
anger
sexual
Classes of Neurotransmitters
- Amino acids:
a. Excitatory: ____ and ____
Na+ entry depolarizes membrane
Important for ____ and memory
Too much glutamate - ____
b. Inhibitory: ____ and ____Cl- entry hyperpolarizes membrane
Throughout CNS, recent evidence suggests signaling in ____ cells too.
____ and ____ are the most widely recognized excitatory and inhibitory neurotransmitters respectively
glutamate
aspartate
learning
excitotoxic
glycine
GABA
non-neural
glutamate
GABA
Receptor for glutamate in dental pulp
The EM picture on the left (A), you can see
____ (Metabotropic glutamate receptor 5), there are axons (labeled by white
arrow heads) here in the human coronal pulp. In the Schwann cell (area labeled S), there are electron dense product. In the cross section on the right (B)- you can see
the ____ neurons and neurotransmitters (labels with *) next to a Schwann
cell (labeled S). So you have these receptors and ____ signaling in your dental
pulp.
mGluR5
unmyelinated
glutamate
Classes of Neurotransmitters
- Neuropeptides (Not inclusive)
____, somatostatin, neuropeptide Y, ____
Very ____neurotransmitters - diffusion to great ____ and still activate receptors at ____ concentrations
Usually act at ____
____ is important in pain transmission.
• Act similarly to a hormone, and \_\_\_\_
substance P
vasoactive interestinal polypeptide (VIP)
potent
distances
low
G-protein coupled receptors
substance P
large
NPY increases in dental pulp with carries
In this picture of neuropeptide Y (NPY) in a dental pulp, you can see that the 1st pic (labeled A) is the control vs. the 2nd pic (labeled B) with carries. And you can see there is an increase in ____ staining (green) the pulp in the carries, with the ____
neuron marker, (so it is within the neurons). So again, you can see an increase in
these ____ when you have a patient with a lot of carries.
NPY
PGP-9.5
neurotransmitters
Classes of Neurotransmitters
- Opioid or opiate peptides:
____, enkephalin
____ neurons and in neurons of the ____
____ or ____ manner depending on the target neuron receptors. Opioids may also act ____ to alter the efficiency of the synaptic output.
Enkephalin pathways are important in ____.
endorphin CNS GI tract excitatory inhibitatory presynaptically dental analgesia
Neuronal transmission D. Presynaptic inhibition
Inhibitory synapses can contact the presynaptic terminals thereby making it more difficult to excite the terminal and release ____.
____ or ____ are the usual inhibitory neurotransmitters. Stimulation of these inhibitory pathways may have relatively ____ effects on the presynaptic membrane.
Presynaptic inhibition can also limit transmission of ____ signals
Presynaptic inhibition can limit ____
neurotransmitter GABA glycine long-term pain pain
Classes of Neurotransmitters
5. Other neurotransmitters:
____, cAMP, cGMP, ____
ATP increasingly recognized for its role in mediating ____ and ____ – general and in oral cavity.
ATP released by damaged tissue to activate ____ receptors on ____ neuron
ATP released at ____, acts on postsynaptic receptors, modulates release from ____ receptors.
• Damaged cells release ATP, neurons have receptors, afferent neuron carries signal, and receptors in dorsal horn going to the thalamus… complex signaling network - because ATP was the first NT from a \_\_\_\_ sense
NO
ATP
pain
inflammation
ionotropic P2X
afferent
synapse
presynaptic
primitive
Summary
1. In the presynaptic neuron, the depolarization from the action potential opens voltage-gated Ca2+ channels which trigger fusion of synaptic vesicles to the membrane and release of transmitter
- After crossing the synaptic cleft, neurotransmitters bind to ____ or ____ receptors to change the membrane potential of the postsynaptic membrane
- The small change in potential following a synaptic event can be modified by ____ and ____ summation to reach ____ for action potential
- A variety of neurotransmitters and their receptors enable complex signaling across the nervous system
ionotropic metabotropic spatial temporal threshold
