NEUR 0010 - Chapter5 Flashcards
What do electrical synapses do?
Allow direct transfer of ionic current from one cell to the next through gap junctions
Where do electrical synapses occur?
At gap junctions
What is a gap junction?
Six connexins (special proteins) form a connexon, and a connexon from each of two cells combines to form the gap junction
How do electrical synapses differ from most chemical synapses?
They’re bidirectional; current can pass just as well either way
What does it mean for two cells to be electrically coupled?
That they’re connected by gap junctions through which electrical current can pass
What advantages does electrical coupling offer?
Very fast and reliable signal transmission; almost instantaneous
Electrical synapses are very common in which part of the mammalian nervous system?
CNS: in almost every part
What happens when an action potential occurs in the presynaptic neuron of an electrically coupled pair?
A small amount of ionic current flows across the gap junction channels into the postsynaptic neuron, triggering a small postsynaptic potential
What is a PSP?
Postsynaptic potential: induced by the small amount of current that flows from pre to postsynaptic neuron when the presynaptic neuron experiences an action potential
How do PSPs illustrate bidirectionality of electrical synapses?
An action potential in Neuron 1 induces a PSP in Neuron 2, but when Neuron 2 undergoes its own action potential, it also induces a PSP in Neuron 1
What is the connection between PSPs induced by presynaptic neurons and action potentials in the postsynaptic neuron?
The PSP itself probably isn’t big enough to trigger an action potential in the postsynaptic neuron, but the postsynaptic neuron is often receiving a lot of PSPs from multiple presynaptic neurons, and the cumulative effect can trigger the action potential (synaptic integration)
What function makes gap junctions particularly necessary/prevalent?
Needing the neighboring neuron activity to be highly synchronized; very common during early embryonic stages
What is the majority of synaptic transmission in mature human nervous system, electrical or chemical?
Chemical
What separates the pre and post synaptic membranes at chemical synapses?
Synaptic cleft: filled with matrix of fibrous extracellular protein to bind the two membranes together
What are the two kinds of vesicles usually found in the presynaptic neuron at a chemical synapse?
Synaptic vesicles (smaller, carry neurotransmitters) and secretory granules (also called dense-core vesicles; contain soluble protein; appears dark in electron microscope)
What are secretory granules?
The larger counterpart to synaptic vesicles: carry soluble protein; also called dense-cored vesicles
What are membrane differentiations?
Dense accumulation of protein adjacent to and within pre and postsynaptic membranes of chemical synapses
What are the membrane differentiations on the presynaptic side of a chemical synapse?
Active zones: proteins jutting into cytoplasm of terminal, look like pyramids; actual sites of neurotransmitter release
What is the actual site of neurotransmitter release?
The active zones: little pyramids of protein along the terminal membrane; the presynaptic membrane differentiation
What is the membrane differentiation on the postsynaptic side of a chemical synapse?
Postsynaptic density; contains neurotransmitter receptors (convert intercellular chemical signal to intracellular signal)
What is the postsynaptic density?
The membrane differentiation of the postsynaptic membrane; contains neurotransmitter receptors
How does one distinguish the different types of synapse in the CNS?
Based on what part of the neuron is postsynaptic to the axon terminal, and based on whether the pre and postsynaptic membrane differentiations are symmetrical or not
What is an axodendritic synapse?
When the postsynaptic membrane is on a dendrite
What is an axosomatic synapse?
When the postsynaptic membrane is on the cell body
What is an axoaxonic synapse?
When the postsynaptic membrane is on the axon of another neuron
Can dendrites ever form synapses with other dendrites?
Only in very specialized situations; called dendrodendritic synapses
What is Gray’s type 1 synapse?
When the membrane differentiation on the postsynaptic side is thicker than the presynaptic side; postsynaptic density thicker than the active zones; usually excitatory
What is Gray’s type 2 synapse?
When the membrane differentiation on the pre and postsynaptic sides are equally thick: postsynaptic density and active zones are symmetrical; usually inhibitory
Which synapse type is usually more excitatory, Gray’s type 1 or type 2? Inhibitory?
Gray’s type 1 (asymmetrical) is excitatory; Gray’s type 2 (symmetrical) is inhibitory
What is a neuromuscular junction?
When chemical synapses occurs between the axons of motor neurons of the spinal cord, and skeletal muscle; the synaptic junction is outside of the CNS
What is the action potential relationship in neuromuscular junctions?
Very fast, and an action potential in the presynaptic motor neuron ALWAYS causes an action potential in the muscle cell it innervates
Why is neuromuscular synaptic transmission so reliable?
Large junction: presynaptic terminal contains large number of active zones, and postsynaptic membrane of the muscle (motor end-plate) contains lots of junctional folds that are packed with receptors
What is the motor end-plate?
The postsynaptic membrane of a neuromuscular junction on the muscle cell’s membrane; contains many junctional folds that have high neurotransmitter receptor density
What are the three main chemical categories of neurotransmitters?
Amino acids, amines, and peptides
What is the difference in storage/secretion of amino acid/amine neurotransmitters vs peptide neurotransmitters?
Amino acid/amine are small and are stored in synaptic vesicles; peptide are larger and thus are stored in secretory granules (dense-core vesicles)
What are the three main amino acid neurotransmitters?
GABA, glutamate, glycine
What are six main amine neurotransmitters?
ACh, Epi, NE, DA, histamine, serotonin
What are nine main peptide neurotransmitters?
CCK, somatostatin, dynorphin, enkephalins, NAAG, Neuropeptide Y, Substance P, thyrotropin-releasing hormone, VIP
What three neurotransmitters mediates fast synaptic transmission in most CNS synapses?
GABA, glutamate, and glycine (GABA, Glu, Gly)
What neurotransmitter mediates fast synaptic transmission at all neuromuscular junctions?
Acetylcholine (ACh)
Why are glutamate and glycine abundant in most neurons, whereas GABA and amines are only made in neurons that release them?
Because Glu and Gly are protein building block amino acids, so all cells use them anyway
How are most AA/A neurotransmitters manufactured?
Synthesizing enzymes for amino acid/amine neurotransmitters are transported to axon terminal; transporter proteins then concentrate the manufactured NT into synaptic vesicles
How are most peptide NTs manufactured?
On ribosomes of RER in the soma: long string of aa’s split in the Golgi, and one of the smaller peptide fragments is the active NT; secretory granules bud off from the Golgi and travel to the axon terminal
What triggers NT release?
Arrival of an AP in the axon terminal; depolarization causes voltage-gated calcium channels in active zones to open: huge influx of Ca++, which signals release of NT from synaptic vesicles
Why is exocytosis of synaptic vesicles so quick after depolarization causes Ca++ voltage-gated channels to open?
Because the Ca++ floods in through the active zones, where a whole bunch of synaptic vesicles are already waiting to unleash their neurotransmitter wrath upon the synaptic cleft; some think they’re “docked” at the active zone
What is “docking” of synaptic vesicles during chemical synaptic transmission?
When the synaptic vesicle’s membrane proteins and the active zone interact; at high Ca++ concentration, the proteins alter conformation to fuse the vesicle membrane and active zone membrane
How does release of peptide NT differ from release of AA/A NT?
Still occurs by exocytosis with Ca++ changes, BUT doesn’t have to occur at the active zones: happens further away, which is why release of peptide NT requires high-frequency trains of action potentials, so that Ca++ can build up enough to reach it
Why is peptide NT release slower than AA/A NT release?
Because the secretory granules aren’t docked at the active side; release by exocytosis further away, and require high-frequency action potentials to build up enough Ca++ to reach it
What kind of action potentials are required for release of peptide NT?
High frequency, so that Ca++ build up can reach the secretory granule docking sites
What are the two main types of NT receptors?
Transmitter-gated ion channels, and G-protein coupled receptors
What are transmitter-gated ion channels?
NT receptors: membrane-spanning proteins, four/five subunits to form a pore; binding of an NT causes conformational change to open the pore
Which shows more ion selectivity, transmitter-gated ion channels, or voltage-gated ion channels?
Voltage-gated; transmitter-gated show less selectivity
What does it mean for an NT to be excitatory?
It opens channels to allow an influx of Na+, bringing the neuron closer to action potential threshold; depolarization
What two ions are ACh-gated channels permeable to?
Na+ and K+, they’re not too picky
What is an EPSP?
Excitatory PSP: transient postsynaptic membrane depolarization caused by the presynaptic release of NT
Synaptic activation of what two transmitter-gated channels causes EPSP?
ACh and glutamate
What does it mean for an NT to be inhibitory?
It opens channels to allow an influx of Cl-, bringing the neuron further from action potential threshold; hyperpolarization
What is an IPSP?
Inhibitory PSP; transient hyperpolarization of the postsynaptic membrane potential caused by presynaptic release of NT
Synaptic activation of what two transmitter-gated channels causes IPSP?
GABA and glycine
Which has faster chemical synaptic transmission, transmitter-gated ion channels or G-protein coupled receptors?
Transmitter-gated ion channels, mediated by AA/A NTs
What are the characteristics/benefits of G-protein coupled receptors over transmitter-gated ion channels?
Slower, and allow for more diverse postsynaptic actions
What are the three steps in G-protein coupled receptor action?
NT molecules bind to receptor proteins in postsynaptic membrane; receptor proteins activate small G-proteins to move along intracellular fact of postsynaptic membrane; activated G-proteins activate effector proteins
What are effector proteins in G-protein coupled receptor transmission?
Can be G-protein gated ion channels; can be enzymes that synthesize second messengers, that can trigger additional enzymes and regulate ion channel function and alter cell metabolism and all that jazz
Why are G-protein coupled receptors called metabotropic receptors?
Because they can activate pathways that trigger widespread metabolic effects
How can you explain the inhibitory/excitatory effects of ACh on the heart vs skeletal muscles?
ACh acts on G-protein coupled receptors in the heart (slow hyperpolarization by way of K+ channel)), but acts on ACh-gated ion channels in skeletal muscle (rapid depolarization, by way of Na+ channel)
What are autoreceptors?
Presynaptic receptors that are sensitive to the NT released by the presynaptic terminal; typically G-protein coupled receptors that stimulate second messenger formation
What is the common effect of autoreceptors?
Inhibition of neurotransmitter release, and potentially neurotransmitter synthesis; allows presynaptic terminal to regulate itself
What type of receptor is usually involved in autoreceptors, transmitter-gated ion channels or G-protein coupled receptors?
G-protein coupled receptors, usually stimulate second messenger formation
What are four ways NT can be cleared from the synaptic cleft?
Diffusion away; reuptake by the presynaptic neuron (can be repackaged or dissembled); reuptake by the glia; destroyed in the cleft itself
How is ACh removed from the neuromuscular junction?
Destruction in the cleft by acetylcholinesterase, released by the muscle cells
What happens if ACh isn’t removed from the neuromuscular junction?
The transmitter-gated channels close anyway, and persists; desensitization: neuromuscular transmission fails
How do receptor antagonists work to inhibit synaptic transmission?
Bind to receptors and block the normal action of the transmitter
What does curare do the synaptic transmission?
Receptor antagonist: blocks the receptors from binding to ACh in skeletal muscle
How do receptor agonists work?
Instead of inhibiting synaptic transmission, just mimic: bind to and activate receptors
What does nicotine do the synaptic transmission?
Receptor agonist: mimics ACh in skeletal muscle (specifically, binds to nicotinic ACh receptors)
What does it mean that postsynaptic EPSPs at a given synapse are quantized?
They’re multiples of the quantum, the number of transmitter molecules in a singly synaptic vesicle and the number of postsynaptic receptors available
What is a miniature PSP?
The tiny response to spontaneously released NT by exocytosis in the absence of presynaptic stimulation
What is quantal analysis, and what is it used for?
Method of comparing mini PSP amplitudes to evoked PSPs: determines how many vesicles released NT during synaptic transmission
What is the difference in NT release at neuromuscular junctions vs in the CNS?
At neuromuscular junction, hundreds of vesicles are released for an EPSP for 40mV or more; in the CNS, maybe only one vesicle will be released, for a much smaller EPSP
What are the two types of EPSP summation?
Spatial and temporal
What is spatial EPSP summation?
Adding together EPSPs that are generated simultaneously by many different synapses on a dendrite
What is temporal EPSP summation?
Adding together EPSPs generated at the same synapse when they occur in rapid succession (kind of snowballing)
What determines the effectiveness of an excitatory synapse in triggering an action potential?
How far the synapse is from the spike initiation zone, and the properties of the dendritic membrane
What is the dendritic length constant?
The distance where the depolarization of the dendritic membrane is 47% of that at the origin; based on logarithms; index of how far depolarization can spread down a dendrite or axon
What does the dendritic length constant depend on?
Internal resistance (resistance to current flowing longitudinally) and membrane resistance (resistance to current flowing across the membrane)
How do internal and membrane resistance affect the dendritic length constant?
Higher internal resistance decreases the dendritic length constant; higher membrane resistance increases the dendritic length constant (prevents “leaks”)
What do internal and membrane resistance depend on?
Internal resistance depends on dendrite diameter; membrane resistance depends on the number of ion channels open
What does the term “excitable dendrites” mean?
That transmission of depolarization down the dendrite to the spike initiation zone doesn’t just depend on internal/membrane resistance; they have voltage-gated ion channels that can amplify small PSPs and “snowball” them towards the spike initiation zone, too
What is shunting inhibition?
When an inhibitory synapse hyperpolarizes the membrane potential, and represents an influx of negative charge as an efflux of positive charge: shunts the positive current flow (for depolarization) outward across the membrane
What is modulation?
The type of synaptic transmission that relies on G-protein coupled NT receptors that aren’t directly associated with ion channels; don’t directly evoke EPSP/IPSP, but modify the effectiveness of the EPSPs generated by other synapses with transmitter-gated channels
What is an example of modulation using NE in the brain?
NE binds to beta receptors: activates G-protein coupled pathway that activates effector protein (adenylyl cyclase) to catalyze AMP into cAMP (second messenger); cAMP stimulates protein kinases to phosphorylate specific sites on cell proteins (in the brain with NE, decreases K+ conductance by closing K+ channels; this increases dendritic membrane resistance and increases length constant)
