AP is generated ______ of presynaptic neurons, and propagates down to the axon terminal.
At the axon hillock
Voltage-gated calcium channel
What type of receptors are located on the end-plate of a muscle cell?
nAChR (ionotropic receptors)
Ionotropic glutamate receptor
What occurs when ACh binds to the nAChR at the end-plate?
Na+ and Ca++ fluxes into the muscle cell, generating a postsynaptic EPSP.
What occurs in a muscle cell when the integrated EPSP of the postsynaptic cell reaches threshold?
Voltage-gated Na+ opens, and an AP is generated.
The brain functions as a _________, primarily connected via ________, and sometimes ________.
Neural cell network; chemical synapses; electrical synapses
In the cortex (hippocampus), a pyramidal neuron forms ________ synapses. The adult brain contains ___-___ ________ synapses.
Several thousand; 100-500 trillion
Postsynaptic neurons integrate synaptic inputs (+/-) by spatial and temporal summation into a ________ code. This code is transmitted to innervated cells.
How does the location of axon C alter the depolarization of the dendrites of the pyramidal neuron?
Depolarization is smaller, and occurs later because it diminishes over time.
2 most common neurotransmitters:
Dendritic spines are small, ________ of dendrite
How do electrical and chemical synapses differ in their directionality?
In chemical neurotransmission, pre- and postsynaptic compartments are ________ in ________ and ________.
Asymmetrical; molecular structure; function
GABAergic synapses are likely to occur ________, while glutamatergic synapses are likely to occur ________ (location).
Dendritic trunk; dendritic spine
The important presynaptic neurotransmission structure is ________, while the postsynaptic neurotransmission structure is ________.
Active zone; post-synaptic density
Neurons function as "computational devices", becauses synapses not only ________ information, but also ________ the AP-coded information.
AP potential pattern in AP burst neurons vs. "tonic" AP neurons:
Burst and tonic neurons allow for neurons to act as ________ by transmitting and transforming AP-coded information.
Pre- and postsynaptic neurons transmit and transform coded information via ________.
Specific subcellular structures (i.e. receptors).
2 types of presynaptic structures:
1. Axon terminal
2. Terminal bouton
T/F: it is impossible for a neuron to be able to release multiple NTs
The main function of the active zone is to ________.
Transform presynaptic APs into NT release.
NT release occurs via the machinery of ________.
Active zones are composed of ________ containing core constituents, such as...
An evolutionarily conserved protein complex; VGCC, t-SNARE, RIM, Munc13. RIM-BP, etc.
4 principle functions of the active zone in NT release:
1. Docking and priming vesicles
2. Anchoring VGCC proteins to the presynaptic membrane, enabling Ca++-mediated fast excitation/release coupling
3. Localizing/anchoring presynaptic proteins and making them exactly opposite the postsynaptic density, via trans-synaptic cell-adhesion proteins
4. Mediating short/long-term presynaptic plasticity
How does the active zone mediate presynaptic plasticity?
Either directly by responding to second messengers (i.e. Ca++) or indirectly by recruiting other proteins such as GPCRs that are responsible for plasticity.
How does a presynaptic terminal differ from a terminal bouton?
Presynaptic terminal: an enlargement that contains vesicles that store neurotransmitter at the end of an axon.
Terminal bouton : different segments of a single axon can be enlarged and form synapses (and then continue).
The synaptic cleft = ____ nm in width.
The general name for proteins that align the AZ directly with the PSD is ________.
Synaptic adhesion proteins
2 synaptic adhesion proteins: ________ and ________.
Neurexin and neuroligin
The presynaptic synaptic adhesion protein is ________, while the postsynaptic adhesion protein is ________.
The postsynaptic density consists of:
1. NT receptors and ion channels
2. Scaffold proteins
3. Signaling proteins
The postsynaptic density lies adjacent to ______ of the postsynaptic membrane, in close apposition to the presynaptic AZ.
The cytoplasmic face
Neurexin and neuroligin are both ______ proteins.
Transmembrane, synaptic adhesion
In the early 1960s, glutamate was initially discovered as _______.
A NT in insects.
***It was not even known that it was one of the 20 amino acids.
In the 1980s, glutamate was recognized as ______.
The primary excitatory NT in the CNS of mammals.
What types of cells can produce glutamate?
ALL cells that can undergo the tricarboxylic acid cycle (TCA) AKA all cells that can metabolize glucose.
TCA is also known as _____.
Citric acid cycle
Glutamate can be converted to glutamine by ________.
Glutamine can be converted to glutamate by ________.
How do glutamine and glutamate differ?
By an amino group. Glutamaine has an extra NH3.
How is GABA formed?
Enzyme that converts glutamate to GABA: _____.
GAD: glutamic acid decarboxylase
Protein that packs glutamate into presynaptic vesicles: ____.
vGluT stands for: _____.
Vesicular glutamate transporters
How many types of vGluTs are there? What are the implications of this?
3 types, vGluT1-3.
Each can be expressed in specific glutamatergic terminals, and therefore you can use them to identify specific brain projections and synapses.
vGluT activity is _______-dependent.
Proton (H+). The synaptic vesicles are more acidic than cytosol.
What is more acidic: the synaptic vesicles, or the cytoplasm of the neuron?
How does vGluT get the energy to pump glutamate into the vesicle?
The v-ATPase pumps H+ against its concentration gradient, vGluT then uses this gradient as an antiporter, by transporting 1 glutamate into the vesicle, and 1 H+ out of the vesicle.
Three pools of synaptic vesicles:
1. Readily releasable pool
2. Reserve/recycling pool
3. Resting pool
_____ AKA recycling pool
_____ AKA spontaneous release pool
Readily releasable pool
Vesicles are already docked at the active zone, and densely packed with NTs.
Not docked at active zone, but densely packed with NT, and can dock at active zone to become a readily releasable pool.
An empty vesicle, that will eventually fill with glutamate via vGluT.
______ is critical for the regulation of synaptic plasticity and homeostasis.
Spontaneous neurotransmitter release.
Calcium entry through the VGCC triggers the ______ (______) of vesicles docked on active zones.
Exocytosis (membrane fusion)
How is the fused vesicular membrane retrieved to form more synaptic vesicles?
NSF protein is ______ (type of protein).
SNAP stands for ______.
Soluble NSF Attachment Protein
SNARE stands for ______.
SNAREs are _____ proteins.
Synaptotagmin is a _____ protein, that functions as a _____.
Transmembrane protein; Ca++ sensor
The _______ pool is especially important for synaptic plasticity and homeostasis.
SNAP binds to ____ and ____.
v-SNARE and t-SNARE, causing the vesicle to fuse with the plasma membrane.
The binding of calcium to ______, triggers the assembly of ______ and ______.
Synaptotagmin; t-SNARE; vSNARE
Where is t-SNARE located?
In the presynaptic membrane of the active zone
The SNARE complex (v-SNARE + t-SNARE) recruits ______ and ______ to form a membrane fusion complex.
Cytosolic SNAP and NSF
The membrane fusion complex consists of:
What occurs when NSF hydrolizes ATP?
1. SNARE complex disassembles
2. Plasma membrane fusion
3. Release of NT
Two ways by which NT molecules are removed from the synapse: ______ and ______
Taken-up, broken down
Which cell types can take up NTs?
1. Presynaptic neurons
2. Postsynaptic neurons
3. Glial cells
_____ are transporters that take up glutamate.
EAATs: excitatory amino acid transporters
The ______ and the ______ of EAATs critically regulate the _______.
Subcellular localization; activity level; kinetics of glutamatergic synaptic response (EPSPs/EPSCs).
Where are EAAT1 and EAAT2 primarily located?
In membranes of glial cells (astrocytes and oligodendrocytes)
EAAT2 is mainly located _____.
What is the major route of taking extracellular glutamate up into cells for reuse?
EAAT2, located in astrocytes
______ is the EAAT expressed in neurons.
EAAT3 and 4
_____ is the major EAAT expressed in the retina.
EAAT5. It is localized to photoreceptors and bipolar neurons
EAAT1 is known as GLAST in rodents, this is known as a ______.
In rodents, the ortholog of EAAT1 is _____.
In rodents, the ortholog of EAAT2 is _____.
In rodents, the ortholog of EAAT3 is _____.
What actually are EAATs?
Membrane-bound pumps ionic pumps that resemble ion channels
Where do EAATs and get their energy from to pump glutamate into the cell?
From the cotransport of ions moving down their concentration gradients. The maintenance of these gradients DOES require ATP though.
What ion cotransport is required for glutamate to be taken up into a cell by EAAT2?
1 K+ is pumped out
3 Na+ and 1 H+ are pumped in
At physiological pH, glutamate's charge is _____.
Which EAAT is essential for glutamate homeostasis in the brain?
Glutamate concentration in the extracellular space:
0.001 mM (or 1 µm)
Glutamate concentration in neurons:
Glutamate concentration in glial cell processes:
Glutamate concentration in synaptic vesicles:
EAAT2 is highly expressed by _______ in _______ regions in the brain.
Astrocyte; most regions in the brain
Under resting conditions, the concentration of glutamate in the extracellular space is ____. After an AP, the concentration of glutamate may reach ____.
0.001 mM, 1-5 mM
Which glial cell takes up the majority of glutamate?
Astrocytes (via EAAT2)
% of glutamate taken up into astrocytes
EAAT1/GLAST is high in _______.
Cerebellar Burgmann cells
What occurs to glutamate in astrocytes?
It is converted to glutamine via glutamine synthetase.
What enzyme converts glutamate to glutamine?
What enzyme converts glutamine to glutamate?
If astrocytes take up the majority of glutamate, how does it get back into the presynaptic neuron?
Glutamate is converted to glutamine in astrocytes (by glutamine synthetase).
Glutamine is released from the astrocytes, and transported back into the neuron by glutamine transporter (GLNT).
_____ transports glutamine from astrocytes to the presynaptic neuron.
Glutamine transporter (GLNT)
Where is glutamine synthetase found?
Where is glutaminase found?
How is glutamate transported from the cytosol into synaptic vesicles?
_______ critically regulates the glutamate-glutamine cycle.
The process of astrocytes taking up glutamate to the time when it is taken back up into synaptic vesicles in the presynaptic neuron is known as:
The glutamate-glutamine cycle
The glutamate-glutamine cycle is part of _______.
Where is GLNT (glutamine transporter) located?
On the membrane of presynaptic neurons