Central Synapse Flashcards
What is synaptic transmission?
The major process by which electrical signals are transferred between neurons and muscle cells or sensory receptors, or between cells within nervous system
Within the nervous system, synaptic transmission usually conceived of as interaction between two neurons that occurs in a point-to-point manner at specialized junctions called____________________.
Synapses
Synapses are categorized into two major groups; what are they?
- chemical
- electrical
Explain electrical synapse
- FAST transmission
- numerous GAP-JUNCTIONS channels that allow ions to flow directly from one cell to another
- DIRECT COMMUNICATION between cytoplasm of two cells
- Transmission is BIDIRECTIONAL
What did this experiment prove ?
The presence of neurotransmitters (chemical synapse)
As you can see we have 2 frog hearts that are connected through fluid transfer only.
First frog heart is being stimulated by vagus nerve (which is parasympathetic) so the heart rate decreases and slows down.
HOWEVER, the second frog heart rate also decreases and slows down even though it is NOT directly stimulated by vagus nerve.
Therefore, the synapse must be chemical; hence, the discovery of neurotransmitters
Explain the Chemical synapse
- ONE-WAY conduction (unidirectional)
- presynaptic terminal is usually the axon terminal , which is packed with small membrane-closed sacs called SYNAPTIC VESICLES that carry NEUROTRANSMITTERS
- presynaptic membrane contains regions called ACTIVE ZONES
- the cell membranes are separated by a SYNAPTIC CLEFT (synaptic gap) = NO DIRECT COMMUNICATION between cytoplasm of the two cells
- neurotransmitters bind to POSTSYNAPTIC RECEPTORS , resulting either in EXCITATION or INHIBITION
Main criteria for a molecule to be classified as a neurotransmitter
- Mediates chemical signaling between neurons
- Must be synthesized or present in the presynaptic terminal
- Must produce response in target cell when released
- Must have specific receptors for it on the postsynaptic membrane
- Must be a mechanism for its removal
- Same response when chemical is experimentally placed on target.
No need to memorize. Just take a quick look.
Ok
What signals for neurotransmitter release?
Calcium entry
How does action potential cause the release of neurotransmitters?
Depolarization of the presynaptic membrane by the action potential = voltage-gated calcium Ca++ channels open
(Extracellular calcium is high relative to Intracellular calcium = entry is favored )
How are neurotransmitters in synaptic vesicles released?
By exocytosis of synaptic vesicles
- these vesicles fuse with the presynaptic membrane at specific sites called active zones
Steps of neurotransmitter release (summary)
Postsynaptic receptors are either _____________________ or _________________.
- Ionotropic receptors (ligand-gated ion channel)
- Metabotropic receptors
Ionotropic VS Metabotropic receptors
Ionotropic receptors : (direct gating)
- FAST transmission
- membrane embedded receptors allow ion passage through their pore
Metabotropic receptors: (indirect gating)
- SLOW transmission
- coupled to a G-protein that initiates second messenger cascades, affecting ion channels ( DOES NOT CONTAIN ION CHANNEL)
Explain Ionotropic receptor (ligand-gated channel)
- binding of the neurotransmitter ligand to its receptor proteins = open ion channels in the postsynaptic membrane
- The gates that regulate these channels are called ligand regulated.
Pentameric ligand-gated ion channel superfamily
This super family includes: ACh, GABA(A), glycine receptors
The receptor has 5 subunits around a central channel
Each subunit has 3 domains:
1. Extracellular (ligand binding domain)
2. Transmembrane domain
3. Intracellular domain
The pentameric ligand-gated ion channel superfamily include:
Nicotinic acetylcholine receptor (nAChR)
Type- A y-aminobutyric receptors (GABA-A-Rs)
Nicotinic acetylcholine receptor (nAChR)
-Ligand-gated ion channel
- in both CNS and PNS
- composed of 5 subunits around central pore (selective to cations)
- binding of 2 acetylcholine (ACh) molecules = conformational change = channel opening and flow of cations (EPSP occurs)
- permeable to Na+ and K+, and some isoforms of Ca++.
Type-A y-aminobutyric acid receptors (GABA-A-Rs)
- ligand-gated ion channels = RAPID INHIBITORY synaptic transmission in human brain
- GABA binds at EC = activates channel = conformational change = open Cl- ion channel = Cl- enters cell (IPSP occurs)
NOTE: glycine receptors use similar inhibitory neurotransmission in the brainstem
True or false
Both GABA and glycine are inhibitory
True
Explain Metabotropic receptors: G protein-coupled receptors
- SLOW transmission
- No ligand = alpha, beta, and gamma G-protein subunits are aggregated together and attached to receptor
- With ligand = alpha subunit dissociates from the beta-gamma complex = alpha OR beta-gamma complex will bind to effector protein and open ion channels
An example of metabotropic receptors :
Muscarinic ACh receptors
Muscuranic ACh receptors require the action of G-proteins
Explain
- ACh binds to its receptor , causing the beta-gamma subunits to dissociate from the alpha subunit
- beta-gamma complex then binds to K+ channel, causing it to open
- outward diffusion of K+ = slowing heart rate
What is next
Neurotransmitters bind to specific receptor proteins , opening ion channels, and producing a great change in the membrane potential called GRADED POTENTIAL.
When neurotransmitter binds to the postsynaptic receptors, the response produced can either be :
- Excitatory postsynaptic potential (EPSP) in the postsynaptic membrane
- Inhibitory postsynaptic potential (IPSP) in the postsynaptic membrane.
Explain the excitatory postsynaptic potential
- opening of specific channels, allowing :
more Na+ and Ca++ to enter cell > K+ to exit cell = graded depolarization - inside the postsynaptic membrane becomes less negative
This depolarization is called EPSP
(And if it reaches the threshold = action potential )
Explain Inhibitory postsynaptic potential
If K+ or Cl- gates open = more K+ to exit OR Cl- to enter = membrane becomes more polarized = GRADED HYPERPOLARIZATION
Inside the postsynaptic membrane becomes MORE negative
This hyperpolarization is called IPSP
In case of inhibitory postsynaptic potential, why does it become more difficult to generate an action potential on this membrane?
The membrane potential moves farther from the threshold depolarization required to produce an action potential
Explain Synaptic integration
Individual excitatory or inhibitory inputs normally produce SMALL change in neuron’s membrane potential
EPSPs generated by most CNS synapses are TOO SMALL by themselves to reach the spiking threshold in the postsynaptic cell.
SOOO…
generally, the summed EPSPs from MULTIPLE synapses are required to reach the threshold and trigger a spike , and once the firing threshold is reached, and action potential is generated.
One EPSP will not trigger an action potential in the postsynaptic neuron, but the summation of several EPSPs may cause the threshold to reach, and an action potential will be generated.
There are two forms of PSP summation; what are they?
Spatial summation
Temporal summation
What is spatial summation?
Summation of PSPs generated simultaneously at many different synapses
What is temporal summation?
Impulses received within a short period of time or added together
Summation of PSPs generated at one synapse
How do we terminate neurotransmitter action?
Through timely removal of transmitters from the synaptic cleft to terminate synaptic transmission
Transmitters are removed from the synaptic cleft by three mechanisms :
- Reuptake
- Enzymatic degradation
- Diffusion
Termination of acetylcholine action
Termination of glutamate action
Glutamate is taken up by specialized membrane transporter proteins into presynaptic terminals and glial cells.
_____________ is the main excitatory neurotransmitter in the CNS
Glutamate
Glutamate activity after its release is strictly limited.
Why??
- to allow normal synaptic transmission
- Prevent cell death
- It is a potent neurotoxin at a high concentration
Summary of synaptic transmission at chemical synapse
Comparison of graded potential and action potentials
