Lecture 12: Synapses Flashcards
Synapse overview
=junctions between and transmission of info between a neuron and its target cells
-target cells may be other neurons (synapse), muscle cells (neuromuscular junction), or gland cells (neuroglandular junction)
Electrical synapse (rare)
-electrotonic current flows from presynaptic neuron to postsynaptic and changes the potential of pot.
Chemical synapse (common)
-action potentials of pre- cause release of chemical messengers, who then bind to specific receptors on post- and activate a signal transduction pathway
transmission from neuron to cell, neuromediator
-synthed in neurons, released in synaptic cleft by presynaptic neuron following depolarization, and binds to receptor on postsynaptic membrane, which transduces the signal to target cell
example: neuromuscular junction (NMJ)
- somatic motoneurons terminate in an arborization of axon branches, called terminal boutons
- location of innervation is called NMJ
- muscle side of NMJ called the motor end plate (MEP), a region of muscle cell membrane that is highly excitable
NMJ: neuromediator=acetylcholine
- neurotransmitter released at the NMJ in skeletal muscle is ACh, and has an excitatory effect
- ACh is also a neurotransmitter in the CNS and PNS (autonomic), and can be excitatory or inhibitory
Synaptic transmission: two pools of neurotransmitters
- Readily releasable pool (RRP)
2.Reserve pool (RP)
both contained in vesicles in synapse
Readily releasable pool (RRP)
- located at the active zone of the synapse
- bound to docking proteins at the synaptic membrane
- ready to be released in the synaptic cleft
Reserve Pool
- bound to the cytoskeleton at some distance from the plasma membrane
- waiting to be docked
Synaptic transmission 2: role of Ca2+ VG channels at axon terminals
Eca2+= 130mv (resting Vm is -70mv)
- action potentials at axon terminal depolarize membrane, opening VG Ca2+ channels, increasing Pca++
- large electrochemical gradient for Ca++ drives them inside the cell
Synaptic transmission 3: Ca++ and release of synaptic vesicles
RRP: ca++ stimulates vesicles bound on docking proteins to fuse with membrane, undergo exocytosis and release neurotransmitters
RP: ca++ stimulates vesicles waiting to be docked to move and bind to docking proteins, allowing neurotransmitters to be ready for release when NEXT AP reaches axon terminal
Synaptic transmission 4: ca++ translates electrical message into chemical message
- higher the frequency of APs, the more frequently membrane is depolarized, opening ca++ VG channels more frequently, increasing intracellular ca++, so more vesicles of neurotransmitters fuse with cell membrane and are released into synaptic cleft and bound to receptors as post-, creating a larger response
- therefore ca++ will transduce the electrical info about strength and length of stim into a chemical message
Magnitude of postsynaptic response depends on:
- concentration of neurotransmitter in synaptic cleft
- number of receptors present in postsynaptic membrane
- affinity of receptors for neurotransmitter
synaptic transmission 5: stopping release of vesicles/regulation of ca++
-APs stop, Ca++ ATPase pumps them out of cytoplasm, and intracellular buffers bind Ca++
synaptic transmission 6: activating transduction pathway of postsynaptic cell
- once released, neurotransmitter binds to receptors in membrane of postsynaptic cell
- when neurotransmitters bind onto their specific receptors, signal transduction pathway is activated and target cell responds
synaptic transmission 7: removing neurotransmitters from cleft:
removed by: passive diffusion, active uptake by presynaptic neuron or astrocytes, or enzymess from cleft degrade them (ie. acetylcholinesterase degrades acetylcholine)
Signal Coding: dendrites and cell body
Strength: coded by amplitude of GP
duration: coded by duration the GP lasts before repolarising back to resting Em
Signal Coding: hillock and axon
strength: coded by frequency of AP
duration: coded by duration of train of AP
Signal coding: synaptic cleft
strength: concentration of neurotransmitter
duration: duration of neurotransmitter release
Diversity of Synapses
- wide variety of neurotransmitters released at synapses of different neurons; some excitatory, other inhibitory
- some neurotrans mod the properties of channels or receptors
- receptors for these neurotransmitters vary among neurons, such that in some a single neurotrans. may excite, while in other it inhibits
inotropic neurotransmitter receptor
=receptor is an ion channel, often ligand-gated; create a fast, short term change in potential, and can be excitatory or inhibitory
metabotropic receptor
NOT an ion channel
- activation initiates a signal transduction pathway that transmits its ignal via secondary messenger
- may affect ion channels, modulate properties of channels or receptors, or affect the transcription of proteins (of receptors, enzymes, or ion channels)
- relatively slow and long term changes
inhibitory neurotransmitters
- cause hyperpolarization (IPSPs: inhibitory postsynaptic potentials)
- make postsynaptic cell less likely to generate an AP
excitatory neurotransmitters
- cause depolarization (EPSPs: excitatory postsynaptic potentials)
- make postsynaptic cell MORE likely to generate an AP
Prozac: a SSRI (selective serotonin reuptake inhibitor)
- a monoanime neurotrans. in the CNS and digestive
- in CNS it is involved in regulation of mood, appetite, and sleep
- present in all animals (ubiquitous)
- linked to depression
- SSRIs used to treat clinical depression, anxiety disorders, and some personality disorders
Mechanism of SSRIs
10% of serotonin released by presynaptic cell is lost, 90% binds to post
- then released and taken up by presynapse for further use
- SSRIs are thought to inhibit the reuptake of serotonin by the presynapse, increasing serotonin concentration in synaptic cleft
- only effective on people severe depression, less so with mild or moderate
cocaine
- dopamine is a catecholamine monoamine neurotransmitter in the CNS
- 5 known dopamine receptors for human brain, DRD1-DRD5, 5 being a “reward” transmitter and affinity for it is 10x greater
- DAT is a transmembrane protein that pumps dopamine from cleft back into presynapse
- cocaine is a serotonin-norepinephrine-dopamine reuptake inhibitor
- cocaine causes dopamine to accumulate in the synaptic cleft
- regular use leads to down-regulation of dopamine receptors in postsynapse
