Synapse definition and classification
- specialized zone of contact at which one neuron communicates with another
- 10^11-10^12 neurons in human brain
- average neuron has 1000 synapses
- 10^15-10^16 synapses in the brain alone
- electrical synapses: junctions between neurons permitting direct, passive flow of electrical current
- chemical synapses: junction between neurons that communicate via secretion of NT
Structure of electrical synapses
- electrical synapses are gap junctions
- gap junctions are sites of close apposition (3nm)
- precisely aligned, paired hemichannels made of connexins
- gap junction made up of 10^3 gap junction channels
- each gap junction channel made up of 2 hemi channels
- each hemmichannel made of 6 connexins
Properties of transmission at electrical synapses
- pores of gap junctions are wide and non selective
- diffusion of ions and other small compounds
- fast latency (<0.1ms)
- post synaptic potential changes have same sign but lower amplitude
- usually bidirectional
Function of electrical synapses
1.Species: cray fish, teleost fish
Connected neuron: motor circuit
Function: fast flight response
- Species: Sea hare
Connected neurons: motor neuron
Function: ink release - Species: Mammals
Neuron: GABAergic interneurons and retinal interneurons
Function: synchronization of activity
Regulation of electrical transmission
- gap junctions frequently closed
- opening regulated by:
- Connexin phosphorylation by kinases
- large differences in membrane potentials
Structural features of chemical synapses
- Presynaptic bouton
- Synaptic vesicles containing NT
- Active zone: specialization where NT exocytosed
- Synaptic cleft: extracellular space between neurons
- Postsynaptic specialization: contains receptors and signalling/scaffolding proteins
Structural diversity of chemical synapses
- Asymmetrical (Gray Type I): mostly excitatory
- Symmetrical (Gray Type II): mostly inhibitory
- small SV with little electron density
- amino acid NTs, Acetylcholine
- Small electron dense SVs
- monoamines
- large dense-core SVs
- peptide NTs
Diversity of chemical synapse location
- axospinous: synapses onto dendritic spins
- excitatory
- structural plasticity + compartmentalization - axodendritic: synapses onto dendritic shafts
- excitatory or inhibitory
-axosomatic: frequently inhibitory
-axo-axonic: inhibitory
-dendro-dendritic: inhibitory
Neuromuscular junction
How AP elicit the release of NT
- AP arrives
- Voltage gated Calcium channels open
- Ca2+ triggered exocytosis of NT
- NT binds to receptor
How NT receptor activation leads to AP
A. Ionotropic: ligand gated ion channels, non selective
-current is fast in onset, decays quickly
B. Metabotropic: GPCRs that initiate opening of ion channels (K+)
-Current is slow in onset, long-lasting
How transmission at chemical synapse is terminated
- Voltage gated Na+ channels inactivate
- K+ channels open -> depolarization
- Calcium channels close after depolarization
- Na+/K+-ATPase, PM Ca2+-ATPase reestablish ion gradients
- NT is removed from synaptic cleft
- Some ionotropic receptors desensitize
- Postsynaptic potential dissipates
Timecourse of postsynaptic currents and potentials
- individual ligand-gated ion channels open for few ms; close as ligand unbinds or desensitizes
- synapse: many channels open simultaneously, close at different times => fast rise time, slower decay time
-post-synaptic potential has a slower rise and decay time due to capacitive property of membrane
Direction and Amplitude of currents/potentials
- flux of ions determined by electrochemical gradient
- if Vm = Erev (reversal potential) no net charge of transfer across membrane
- if VmErev, efflux of cations (influx of anions)
- outward current
-the greater the difference between Erev and Vm, the greater the driving force, greater synaptic current
I=g*(Vm-Erev)
-g=conductance of synaptic ion channels
Excitatory postsynaptic currents and potentials
- EPSCs and EPSPs if they facilitate post synaptic AP
- excitatory if Erev is more positive than AP threshold
Inhibitory postsynaptic currents and potentials
- IPSCs and IPSPs inhibit generation of AP
- inhibitory if Erev is more negative than AP threshold
- Erev hyperpolarization
- Vrest shunting inhibition
Spatial summation of EPSPs
- EPSPs derived from activation of single synapses cannot elicit APs by themselves
- AP threshold can be reached through spatial summation of simultaneously activated excitatory synapses
- inhibitory input contributes also
Effects of dendritic cable filtering
-synapses on distal dendrites are at a disadvantage of eliciting AP in axon hillock due to electronis decay as EPSP is propagated to initiation site
Voltage gated conductance in dendrites canamplify EPSP
- in many neurons, coincident activation of clustered excitatory synapses can lead to opening of dendritic voltage gated sodium or calcium channels
- resulting dendritic spike amplifies EPSP
