Synapse II Flashcards
What is the major excitatory neurotransmitter of the brain?
GlutaMATE
What is the major inhibitory neurotransmitter of the brain?
GABA
Most projection neurons such as long axons and linking brain areas release what as a neurotransmitter?
GlutaMATE
Most interneurons such as short axons, local circuit, axons within the brain area, release what as a neurotransmitter?
GABA
Both GlutaMATE and GABA are synthesized from ____ by enzymes within the _______
amino acids; axon terminal
Both GlutaMATE and GABA are actively transported into _______
synaptic vesicles
Both GlutaMATE and GABA activate ____ and ____ receptors that are selective for each transmitter
ionotropic; metabotropic
After release, both GlutaMATE and GABA are actively transported ____ of the synaptic cleft to terminate the action
out
Pyramidal neurons make up ___% of cortical neurons while Interneurons make up ___% of cortical neurons.
80%; 20%
Pyramidal neurons use which neurotransmitter?
glutaMATE
Interneurons use which neurotransmitter?
GABA
Specific transporters pump glutaMATE and GABA into ______. After release, specific transporters then pump them out of the synaptic cleft in order to ____ the action.
vesicles; terminate
Where are GlutaMATE and GABA also transported into?
Glia
Glia are converted to ____ which is then transported back into the neurons and converted back into what?
glutaMINE; glutaMATE
GABA is synthesized from glutaMATE in one extra step by which enzyme?
GAD (glutamic acid decarboxylase)
What are the 2 main subtypes of ionotropic glutaMATE receptors?
AMPA and NMDA
Both AMPA and NMDA are present at the same ______ synapses and are nonselective ____ channels
glutamatergic; cation
AMPA receptor:
- Bind of glutaMATE ____ the channel
- Na+ flows ___ the postsynaptic neuron (down electrochemical gradient)
- K+ flows ___ and has a ____ drive on ion; ___ current
- Postsynaptic neuron __-polarizes
- _PSP
- opens
- into
- in; weaker; less
- depolarizes
- EPSP
NMDA receptor:
- Ion channel pore of NMDA receptors is ____ by ____ ions at rest
- If the __-synaptic neuron fires, and the ___-synaptic neuron is at resting membrane potential, glutaMATE opens NMDAR but __ current flows thru channel
- If the __-synaptic neuron is depolarized, and the ___-synaptic neuron fires, NMDAR opens and __ ions are expelled from the pore
- __ ions flow through NMDAR into the __-synaptic neuron
- Calcium activates enzymes that lead to insertion of more ____ receptors in synapse
- Synapse becomes ____, which causes a larger _PSP associated with synaptic plasticity/learning
- blocked; Mg2+
- pre-; post-; NO
- post-; pre-; Mg2+
- calcium; post-
- AMPA
- Stronger
What is excitotoxicity? What is its clinical application?
Pathologically high neurotransmitter levels which leads to excess stimulation of receptors
Stroke
During stroke, what rises (extracellular) rapidly due to hypoxia-ischemia (blocked blood flow to cells/organs)?
glutaMATE
Over-activation of what results in excessive influx of calcium ions to a level that activates enzymes to trigger cell death?
NMDAR
Blocking NMDAR lessens neuronal death in ___ stroke, but not ____ potentially due to incorrect dosage or insufficient early timing post-stroke
animal; human
NMDAR antagonists mimic the clinical symptoms of which mental disorder?
Schizophrenia
In Schizophrenia, it’s been recently studied that there seems to be a link with the disorder and mutations involving genes that play a role in ____ synaptic function
NMDAR
MGluRs are considered to be ____tropic receptors
metatropic
MGluRs have many ____
subtypes
MGluRs are located at synapses on dendrites, cell bodies and on __synaptic terminals
pre
MGluRs modulate the activity of ion channels and other proteins influencing the electrical ____ of neurons
excitability
MGluRs can exert excitatory OR inhibitory effects on ___synaptic neurons
post
GABA is considered to be a ____tropic receptor
ionotropic
With GABA, there is a high concentration of ___ outside the neuron and a ___ mV charge inside to counteract it
Cl- ; -70
Binding of GABA to GABA-A receptor ___ Cl- selective ion channels
opens
Equilibrium potential for Cl- is ___mV. Resting membrane potential is close to that at about ___mV, which means the drive on Cl- is ___ at resting potential.
-70; -65; weak
If Cl- channels are OPEN, and other excitatory synapses start to DEPOLARIZE the neuron, Cl- ions will do what? What is this called?
Move into the neuron and hold its membrane near -70mV
Shunting inhibition which prevents the neuron from being excited
GABA-B is considered to be a ___tropic receptor
metatropic
GABA-B ___neuronal excitability because it ___ the K+ channels
inhibits; opens
GABA-B ___ neurotransmitter release by closing the voltage-gated ___ channels
inhibits; calcium
Seizures reflect insufficient inhibition of what?
GABAergic local circuits
Excessive synchronization of cortical neurons results when there is not a sufficient amount of _____ / loss of ____/ increased _____ levels, which can cause seizures
GABA-A binding; GABA neurons; glutaMATE
Prolonged, untreated seizure activity leads to additional damage to ____ networks (excitotoxicity)
cortical
Anxiety disorder and panic disorder is associate with reduction in which receptor binding?
GABA-A (and general reduced GABA levels)
GABA drugs are most commonly used for purposes such as anti-___, ___-lytic, and adjunctive use for situations involving ______
- Anti-seizure
- Anxiolytic
- Anesthesia
Normal release of GABA is required in _____ receptor positive allosteric modulators, as they enhance already existing GABA and its actions
GABA-A
Barbiturates such as phenobarbital, pentobarbital and thiopental ___ the duration of Cl-ion channel opening of ____ receptors in response to GABA.
increase; GABA-A
What are the risks of Barbiturates?
Severe risk of respiratory, cardiovascular and CNS depression. Severe risk of dependence.
Benzodiazepines such as diazepam (valium), lorazepam and midazolam ____ the frequency of Cl-ion channel opening of ____ receptors in response to GABA.
increase; GABA-A
Nearly all neurons receive both _____ and ____ synaptic input
excitatory; inhibitory
EPSPs and IPSPs sum in the dendritic tree and cell body to determine whether the ___synaptic neuron will fire an action potential
post
The action of an EPSP or IPSP depends on the _____ it binds to and activates
receptor
