1: Synaptic Mechanisms Flashcards
Describe the basis for the concept of excitation versus inhibition with respect to synaptic transmission.
NT themselves are NEITHER excitatory nor inhibitory
—-The interaction of a given NT with a specific receptor determines inhibition versus excitation
Excitation: action of NT drives Vm toward a value that is MORE DEPOLARIZED than the threshold potential for generating an AP
Inhibition: action of NT KEEPS Vm from reaching threshold potential
List the fundamental steps in chemical transmission. (4)
- NT stored in presynaptic vesicles
- Depolarization -> open Ca channels -> Ca-dependent exocytosis
- Activation of postsynaptic receptors
- Termination
List three major excitatory ionotropic receptors and two major inhibitory ionotropic receptors.
Excitatory
- Nicotinic ACh receptors
- Glutamate receptors (NMDA, AMPA, Kainate)
- Purinergic receptors (adenosine, ATP)
Inhibitory
- GABA type A receptors
- Glycine receptors
Describe the difference between an ionotropic and metabotropic receptor, with specific reference to time course and specificity of action.
Ionotropic receptors: ligand-gated ion channels
- -Time course: msec
- -Specificity of action: allow ion to flow down its concentration gradient
Metabotropic receptors: GPCRs; promote activation of second messenger signaling pathways
- -Time course: msec to hours
- -Specificity of action: can have a multitude of effects on a range of second messenger systems
Describe the physical structures that allow electrical coupling between neurons or neurons and non-neuronal cells. Where are these common?
Gap junctions: specialized structures between cells that permit direct current flow and the passage of small ions that have signaling capabilities from one cell to the next
-Channel = connexon, build from 6 connexins
Common in developing tissue to allow coordinate development (-> cells function as a group)
-Also found in adult cochlea
What receptors are found at the neuromuscular junction?
Nicotinic AChR in the postsynaptic muscle cells
True/false: While a typical neuron in the CNS receives tens of thousands of inputs from a host of different presynaptic partners, a single muscle fiber is innervated by a single presynaptic axon (though each axon may contact more than one fiber [motor unit])
TRUE!
Describe the physical basis for mean quantal content and its importance in synaptic transmission.
M = n x p (m) = number of vesicles (n) x probability of vesicles being released (p)
Provides a critical mechanism by which synapses adjust their efficacy
- -Low in CNS -> basis for synaptic plasticity
- —Changes in m -> changes in plasticity -> adaptation to environment, optimized behavioral outputs
Define active zone. How do they function in response to APs?
On the presynaptic side, structures in which there are rows and rows of vesicles containing NT
-Located next to voltage-dependent calcium channels (VDCCs)
Depolarization -> rapid influx of Ca -> highly localized trigger for vesicle fusion and exocytosis of NT
What are postsynaptic specializations that maximize the safety factor and removal of ACh at the NMJ?
High densities of receptors are directly aligned with presynaptic active zones
-Surrounded by high densities of voltage-gated Na channels -> APs -> excitation-contraction coupling
Postsynaptic fold forms a funnel that directs free ACh down into it
-Has AChE to hydrolyze ACh for terminating its action
Describe “safety factor.” Where is it high and why? Where is it low and why?
Safety factor: the fidelity of transmission across a synapse
High at neuromuscular junction (1:1): each presynaptic AP gives rise to a postsynaptic AP
- Important because if you need to jump out of the way of a car, muscles need to respond
- High because of high mean quantal content and highly specialized organization that optimizes action of NT
Low at central synapses: need modulation and plasticity
- Single inputs by themselves can’t drive the system
- Need integration of many inputs to have information continue along a given pathway
What is the function of SNARES?
SNARES: located in synaptic vesicle membrane and in presynaptic terminal membrane
-Function in calcium-dependent vesicle fusion
Describe the molecular mechanism by which botulinum and tetanus toxins have their effects on neurotransmission.
Both work by proteolyzing SNARES -> blocking excocytosis
Botox: blocks synaptic transmission in motor neurons
Tetanus: retrogradely transmitted to inhibitory interneurons, which they inhibit (released inhibition of motor neurons -> activation)
**Describe the fundamental basis of reversal potential. How does it vary with development or disease?
The action of any NT acting at its ionotropic receptor will be to drive the membrane potential of the postsynaptic cell towards the reversal potential for that receptor.
Example: GABA receptor action changes during development
- Early in development - Cl transporter NKCC1 expressed -> [Cl]in is HIGH
- —GABA signaling -> depolarization -> EXCITATORY
- Later in development - Cl transporter KCC2 expressed -> [Cl]in is LOW
- —GABA signaling -> hyperpolarization -> INHIBITORY
Describe reversal potential in the context of the nicotinic ACh receptor. Is this receptor excitatory or inhibitory?
NAChR permeable to both Na AND K
-PNa is slightly > than Pk, so reversal potential is closer to that of Na, at 0 mV
Excitation because 0 mV is > than AP threshold (~45 mV)
