Synaptic Transmission

Question 1

Neuronal morphology

Answer 1

• neurons are specialized to rapidly send and receive info
• dendrites-tapered processes arising from the cell body that greatly increase the receptive surface; membranes have receptors for transmitters and voltage gated ion channels that can amplify the graded synaptic signal
• cell soma- surrounds nucleus and contains the ER, Golgi, performs house keeping functions-membrane contain receptors that bind chemical transmitters released by afferent neurons
• axon
• presynaptic terminals

Question 2

Axon

Answer 2

• single thing processes arising from the cell body at the axon hillock
• transmits all or none action potentials to the terminals after integrating transmitter mediated bioelectrical changes received in the dendrites and cell body
• some azons can be a meter or longer in length containing 1000 times as much cytoplasm called axoplasm as cell body
• many axons are surrounded by a glial-derived myelin sheath which greatly increases the speed of impulse propagation via the process of saltatory conduction

Question 3

Presynaptic terminals

Answer 3

• specialized structures that convert electrical signals propagated down the axon (action potentials) into chemical signals (neurotransmitter), released from presynaptic vesicles and transmitted to the target cell at the synapse (the point of contact between the pre- and post- synaptic neuron/target cell)
• postsynaptic potentials differ from action potentials; they are small graded changes

Question 4

Axoplasmic transport

Answer 4

• axoplasm contains parallel arrays of microtubules and neurofilaments that provide structural stability and a means to transport materials back and forth between the cell body and presynaptic terminals
• fast axoplasmic transport occurs between thecell soma and presynaptic terminals in both anterograde and retrograde directions
• cancer patients -> microtubule disrupting agents -> develop peripheral neuropathies due to gradual vesicle depletion especially in axons innervating distal muscles
• microtuble motor kinesin mediates fast anterograde transport of mitochondria and vesicles from soma to terminals, wherease dynein mediates fast retrograde transport of degraded vesicular membranes and absorbed toxins/viruses/growth factors from terminal to soma

Question 5

Electrical synapses provide speed and synchony

Answer 5

• are extremely fast and most are bidirectional- they allow direct passive flow of electrotonic current between cells via specialized elements called gap junctions
• gap junctions are comprised of intramembrane channel proteins called connexins- to hemi channels termed connexons combine to form a gap junction between two cells
• current flow changes the postsynaptic membrane potential, which can lead to generation of an action potential
• pores are larger than voltaged gated or ligand gated channels- so there is unselective diffusion of ions and substances such as ATP and metabolites

Question 6

Chemical neurotransmitters

Answer 6

• present in the presynaptic terminal
• released in a voltage and calcium dependent manner (calcium is high outside and low inside cells)
• specific receptors present in postsynaptic target cell
• means to inactivate the transmitter (eg enzymatic breakdown/AChE or re-uptake via pumps/glutamate/GABA

Question 7

Chemical synapse in synaptic transmission

Answer 7

• transmitter molecules are synthesized and packaged in vesicles
• an action potential arrives at the persynaptic terminal
• depolarization of terminal opens voltage gated calcium channels
• increased calcium in terminal triggers vesicle fusion
• transmitter diffuses across cleft and binds to postsynaptic receptors
• a postsynaptic response occurs
• transmitter molecules are cleared/inactivated by enzymatic degradation, uptake, or diffusion

Question 8

Synapses

Answer 8

• presynaptic terminals have mitochondria and numerous vesicles
• some vesicles are docked in active zones
• these vesicles were preferentially released in response by action potential, activation of voltage sensitive calcium channels and influx of calcium
• the postsynaptic density was an area of electron dense areas with many receptos
• glucose is major source of energy in brain and neurons, the presynaptic terminals consume most of the energy- fMRI

Question 9

Exocytosis and vesicle fusion

Answer 9

• neurotransmitter release from presynaptic terminal exocytosis
• calcium dependent process involves tight interaction of proteins on the vesicle membrane (V-SNARES- synaptobrevin and Synaptotagmin) with proteins on presynaptic target membrane (T-SNARES- SNAP-25 and syntaxin)
• vesicle membrane that has fused to the presynaptic membrane is recycled through endocytosis

Question 10

Botulinum toxin

Answer 10

-causes muscle weakness by cleaving SNAP-25 or synaptobrevin proteins in the presynaptic terminal of alpha motor neurons

Question 11

Chemical transmitters

Answer 11

• numerous chemical transmitters: glutamate, acetylcholine, norepinephrine, dopamine, GABA, and glycine
• others are large peptides such as enkephalins and vasoactive intestinal polypetide
• depending on chemical structures and receptor interactions: rapid (ligand gated NMDA, AMPA, nicrotinic cholinergic receptors); moderately (metabotrophic glutamate and muscarinic cholinergic receptors); or slowly (receptors for various peptides and proteins) with time courses ranging from msec to days

Question 12

Ionotrophic receptor

Answer 12

• contain an ion channel as part of their structure and transmitter binding triggers a rapid response
• nicotinic ACh receptor channel activation-> membrane depolarization-> action potential excitation-> muscle contraction

Question 13

Metabotropic Receptor

Answer 13

• commonly linked to G proteins that transduce a slower biochemical signal
• muscarinic ACh receptor activatiom
• release of alpha-GTP and beta-gamma from the heterotrimeric G proteins -> activation of inward rectifier K+ channel by beta gamma -> membrane hyperpolarization -> decrease in heart rate

Question 14

Postsynaptic potentials-

Answer 14

• produced through conductance changes due to ion channel openings (and sometimes closings) lead to ionic current flow through the channels that in turn lead to changes in the membrane potential
• excitatory PSPs (EPSPs) increase the probability that an action potential will be triggered whereas inhibitor PSPs (IPSPs) decrease the likelihood
• resting neuron: -65mV
• Excited neuron- less negative intraneuronal potential caused by sodium influx -45mV
• Inhibited Neuron- inhibited state, more negative intraneuronal membrane potential (-70mV) cased by K efflux, Cl- influx or both

Question 15

Glutamate

Answer 15

• major excitatory transmitter in the brain
• binding of glutamate to specific ligand-gated ion channels in the target cell produces both fast and slow depolarizing responses (EPSP or currents EPSCs) because distinct receptors
• AMPA- selectively activated- mediate a fast EPSP via the flow of Na+ and K+ ions
• NMDA receptor channels selectively activated by NMDA and mediate a slower component of EPSP via the flow of Na+, K+, Ca2+ (do not open unless the membrane is sufficiently depolarized b/c they are blocked in a voltage dependent manner by Mg2+
• metabotropic glutamate receptors are even slower- because G-protein linked receptors

Question 16

GABA

Answer 16

• major inhibitory transmitter in the brain
• binds to ionotrophic and metabotropic receptors
• binding of GABA to specific ligand gated ion channels in the target cell produces hyperpolarizing responses called IPSPs
• GABA-A receptor channels mediate a fast IPSP via the flow of Cl- ions down their electrochemical gradient
• drug pentobarbital elicits a larger IPSP when GABA is present because it increases the channel open time/single channel current
• GABA-B receptors are slower in transducing a signal because they are G protein linked

Question 17

Neurons

Answer 17

• human brain 100 billion neurons, and each neuron integrates information from numerous synapses
• the EPSP in an individual excitatory synapse may be only a fraction of a millivolt (below the threshold needed to trigger an AP)
• neurons in the CNS are innervated by thousands of synapses so these local potentials can sum together in space and time to reach the threshold needed to trigger an all or non AP
• an AP in one neuron is transmitted to another neuron at the synapse-> terminal regions of axons branch to form boutons- myelination lost where bouton fuses with presynaptic membrane, released neurotransmitters diffusion and bind to receptors on postsynaptic membrane

Question 18

Synaptic potential changes

Answer 18

• most dendrites don’t transmit APs because they dont have Na+ channels and their threshold is too high
• small depolarizations or hyperpolarizations in dendrites and cell somas are local passive events
• they spread only a few millimeters and get smaller father away
• temporal and spatial effects- cable theory
• dendrites long and membranes leakey- large amount of potential lost by leakage- decremental conduction

Question 19

Temporal stimulation

Answer 19

• excitatory postsynaptic potentials (EPSPs) produced at one synapse by two sequential action potentials are shown
• in cell membrane with a shorter time constant the first EPSP terminates before the second is produced
• when the membrane has a longer time constant some of the depolarization from the first EPSP is still present when the second occurs and individual depolarizations can summate

Question 20

Spatial summation

Answer 20

• action potentials in two neurons produce excitatory postsynaptic potentials (EPSPs) at their synapses, which propagate by passive conduction to the soma and axon hillocks
• when space constant of the cell membrane in the dendrite is shorter, the EPSP from synapse 1 decays back to the resting membrane potential value before propagating to the site of synapse 2
• when the cell membrane has a longer space constant, the EPSP from synapse 1 is able to propogate further along the membrane and can summate with the EPSP from synapse 2, resulting in more depolarization to propagate to the soma and azon hillock

Question 21

Temporal and spatial summation at synapses determine probability of AP generation

Answer 21

• neurons integrate complex info
• EPSPs generated from different presynaptic inputs can combine to generate large potentials
• the process involves the summing of simultaneous postsynaptic potentials from multiple terminals- spatial summation
• temporal summation occurs when EPSPs from the same cell arrive in rapid succession
• axon hillock has a very high density of voltage gated Na+ channels