Synapses

Synaptic cleft

very small space for communication

neurotransmitter from pre-synaptic neuron to receptors on post-synaptic cell

200-300 angstroms

Types of Synapses- Gray's type I

round clear vesicles, usually excitatory

Types of Synapses- Gray's type II

flattened clear vesicles, usually inhibitory

Types of Synapses- Specialized synapses

2 or more post-synaptic cells

e.g., ribbon synapses of retina

Synaptic Vesicles - Electron-Lucent Vesicles

a) Small spherical

• Gray’s type I (Acetylcholine; amino acids)

b) Small flattened

• Gray’s type II (GABA; glycine)

c) Coated, pinocytotic (vesicles are labeled by spikes)

Synaptic Vesicles - Electron-Dense Vesicles

a) Small and medium for catecholamines (epinephrine/norepinephrine)

• Often seen in sympathetic nerve endings

b) Large for peptides

• E.g., ADH or oxytocin

c) Very large for enzymes

• Peroxisomes, secretory enzymes

Basic Mechanism of Chemical Synapse

• Action potential arrives at the presynaptic terminal

– Entire ending is depolarized

• Calcium channels open; calcium ions enter and activate vesicle binding to presynaptic membrane

– Calcium influx triggers enzymatic events

• Neurotransmitter released, diffuses across synaptic cleft

– Each vesicle may contain up to 10,000 molecules of neurotransmitter

• Membrane potential of postsynaptic neuron changes

– Can bind to more than 1 type of receptor, with different physiological effects

– Binding often influenced by presence of ions, drugs

Membrane potential of postsynaptic neuron changes

– Movement of positive ion inside = depolarization

– Movement of positive ion outside = hyperpolarization

– Opposite for negative ions

Voltage-gated channel

Voltage change opens the channel

Ligand-gated channel

Binding of ligand opens the channel

Excitatory Postsynaptic potentials (EPSP)

– Postsynaptic receptor opens ion channels for sodium (not specific to sodium, just needs to depolarize, i.e efflux of Cl-)

– Sodium ions enter cell causing depolarization

– Amplitude is typically 1 mV

– Duration 2 to 15 milliseconds

Threshold must be met to fire action potential

Inhibitory Postsynaptic potentials (IPSP)

– Postsynaptic receptor opens ion channels for chloride and/or potassium

– Ions move in (chloride) and/or out (potassium), causing hyperpolarization

– Amplitude may be apparently zero to 1 mV

– Duration 2 to 15 milliseconds

Spatial summation

increased number of synapses of same type (excitatory or inhibitory) activated simultaneously

Same time but different location

– A single axon often has multiple terminals on dendrites of a single postsynaptic cell

– More important inputs have more terminals

Temporal summation

repeated activation of same synapse within a brief time (up to 100/second)

Not simultaneous but same location

– Multiple action potentials increase amount of transmitter release

– Amplitude as well as duration of PSP can be increased

• Effect of each synapse depends on proximity to axon hillock/initial segment, due to decrease in amplitude with distance

– Exponential decay with e-fold (63%) loss in about 100 microns

• Synapses at initial segment have powerful control over neuron's activity (inhibitory synapses tend to have most control)

• Overall activity of a neuron is summation of all excitatory, inhibitory, spatial, and temporal influences

Axonal Transport of Materials from Cell Body to Synapse

Axons & terminals require transport for all proteins, many membrane components

• Fast (orthograde) transport moves large particulate and non-soluble materials at a rate of 400 mm/day

• Slow transport: generally dissolved substances at a rate of 1 mm/day

Forward direction from cell body to synaptic terminal.

• Retrograde transport recycles materials, carries chemical signals at 200 mm/day

• Both orthograde and retrograde transport have been utilized to study connections between parts of the nervous system by injection of tracers