Lecture 6 Flashcards
These increase neuronal surface for synaptic contact:
dendrites
Where do afferent axons synapse in CNS?
nerve cell bodies and dendrites
T or F? Input to neurons in the CNS is always excitatory.
F. either
Small protrusions off of dendrites:
spine
Is the shaft synapse excitatory, inhibitory, or either?
either
Is the spine synapse excitatory, inhibitory, or either?
only excitatory
Is the somatic synapse excitatory, inhibitory, or either?
mainly inhibitory
Is the axoaxonic synapse excitatory, inhibitory, or either?
inhibitory
This type of synapse is prevalent in CNS during development - less so in adult CNS:
Electrical
This type of synapse is the only mode of transmission bw cardia and smooth muscle cells:
electrical
What are electrical synapses found in mature neurons?
in interneuronal connections
The synaptic efficacy of this/these type(s) of synapse can be modulated;
chemical
A molecule must be under ____ Daltons to pass through a GAP jucntion:
1000
Coupling bw cell connected via GAP junctions is both:
electrical and metabolic
T or F? The CNS ECM in the synaptic clefts.
F. No ECM
Which are narrower, clefts of the NMJ or clefts of the CNS synapse?
CNS synapse (no ECM)
Which has a greater postsynaptic density, excitatory or inhibitor bouton?
excitatory
What anchors transmitter receptor and intracellular signaling machinery in excitatory synapse?
prominent postsynaptic density
This type of vesicle recycling is involved in high frequency firing:
Kiss-and-run fusion
2 types of vesicle recycling:
Kiss-and-run and fusion and collapse
Step in competence maturation of fusion vesicles:
docked, primed, cocked, armed
What is required for vesicle docking?
Ca binds to receptor and changes conformation
What is the fusion event mediated by?
snare proteins
This snare protein is on the vesicle membrane:
V-snare
This snare protein is on the target membrane:
T snare
These are targets of botulinum:
SNARE proteins
V-snare:
synaptobrevin
T-snare:
syntaxin and SNAP-25
Calcium sensor:
synaptotagmin
T or F? Once a vesicle is armed it can go either pathway, Kiss-and-run or fusion and collapse.
T
This type of vesicle recycling has a readily releasable pool:
Kiss-and-Run
What happens if SNARE proteins encounter botulin toxin?
fusion and exocytosis is prevented, blocking transmission
T or F? The whole vesicle is collapsed in both Kiss-and-run and fusion and collapse.
F. Not in Kiss-and-run
2 major classes of ion channels:
voltage and ion gated
Where does neurotransmitter bind in order for a channel to open?
to a receptor on the ion channel
Are “fast neurotransmitters” used with ligand-gated channels, voltage-gated channels, or either?
ligand-gated
Are “slow neurotransmitters” used with ligand-gated channels, voltage-gated channels, or either?
either
This type of neurotransmitter mediates synaptic transmission:
“fast neurotransmitters”
This type of neurotransmitter modulates synaptic transmission:
“slow neurotransmitters”
Do GPCRs act with “slow neurotransmitters” or “fast neurotransmitters?”
“slow neurotransmitters”
T or F? Ligand-gated ion channels are metabotropic.
F Ionotropic
Are GPCRs ionotropic or metabotropic?
metabotropic
What does the G-protein bind to once activated?
effector protein
This type of neurotransmitter can trigger a 2nd msg pathway and regulate phosphorylation:
“slow neurotransmitter”
2 major families of ligand-gated channels:
- Glutamate receptors
2. GABA (inhibitory - CNS), ACh, Glycine (check)
Where are both the ligand binding domain and the C terminal located with ACh, GABA, and glycine receptors?
extracellularly
Where is the C terminal located in glutamate receptors?
intracellularly
How many subunits do GABA, ACh, and Glycine have?
5 subunits, each w/ 4 trans domains
How many subunits do glutamate receptors have?
4 subunits, each w/ 3 transmembrane domains
How many binding sites does the glutamate receptors have?
2, N terminal and 3rd and 4th exc loop
Where is the C terminal of the glutamate channel located?
intracellularly
What helps anchor the glutamate receptor, providing stability and mobility of the receptors?
proteins at postsynaptic site
Major NT in the CNS for excitation:
glutamate
Major NT at the NMJ:
ACh
What ends the action of NT(glutamate) in the CNS?
reuptake by terminals glial cells
Glutamatergic receptor types:
AMPA and NMDA (agonists)
T or F? AMPA and NMDA are both antagonists.
F. agonists
AMPA
- permeable to Na and K
2. EPSP
NMDA
- permeable to Na, K and Ca
- complicated IC signaling
- EPSP
- blocked by Mg
Mg removal:
via depolarization
NMDA activation:
- presynaptic activation (release T)
- postsynaptic activation (remove Mg)
glutamate receptors
- ionotropic: AMPAR and NMDAR, have intrinsic channels
- metabotropic: g-coupled
AMPAR:
fast transmission
NMDAR:
- coincidence detector
- regulate synaptic plasticity
- key player in learning
glycine:
- co-agonist for NMDA to open channel fully
- increase conductance
PCP:
- antagonist for NMDA receptor
- binding site
Hebb’s rule:
learning and memory depend on neurons modifications
excitotoxicity:
excessive inflow of Ca through NMDAR channels
glutamate pathway:
released -> bind at postsynaptic -> channels activated -> Na/K flux -> uptaken by excitatory AA transporters on glial cells -> becomes glutamine -> back to nerve terminal -> conversion
EAAT:
uptakes 90% of glutamate
GABA:
inhibitory in CNS
GABA:
termination reuptake by terminals and glial cells
glycinergic receptors
- postsynaptic in spinal cord and brain
- antagonist
GABAergic receptors
- postsynaptic in brain
- ionotropic
- antagonist
antagonist
block inhibitory signal -> potential very - -> hyperpolarization
GABA receptors binding sites
- for GABA
- for steroids: modulators
- for barbiturates: anesthetics
glutamate receptors location (AMPAR, NMDAR)
- postsynaptic densities
- dendritic spines and shafts (distal)
GABA receptors location
- soma (AP trigger zone)
- proximal dendrites
- limited inhibitory transmission so better location
EPSP
due to Na influx
IPSP
due to Cl influx
motoneuron
- 1 cell body with many dendrites
- dendrites serve as input segments
- 1 axon = 1 output
motoneuron synapse distribution
- 80% on dendrites
- 20% on cell body
divergence of motoneuron axon branches
governed by size of motor unit
glutamergic input
excitatory
GABAergic input
inhibitory
ACh release
- excitatory
- control of contraction
Patella tendon reflex pathway
- stretch stimulus -> stretch receptor in extensor muscle -> afferent activated -> excitatory monosynaptic and inhibitory disynaptic activated
excitatory monosynaptic
- extensor contraction stimulated
- release glutamate
- EPSP, stimulate dorsal root
inhibitory disynaptic
- flexor contraction prevented
- interneuron innervates motorneuron
- release glycine
- IPSP, stimulate posterior root
5 subunit ligand-gated channel
- NAChR, GABA R
- inhibitory in CNS
- each subunit = 4 TM
- C terminal is EC
4 subunit ligand-gated channel
- glutamate R
- excitatory
- 3 TM with IC loop
- C terminal is IC