Functional Anatomy Excitatory Synapses Inhibitory Synapses

Synaptic Transmission Synapse Point of impulse transmission between neurons Impulses are transmitted from pre-synaptic neuron to: Cell body, dendrite or axon of another neuron A muscle Gland 19-Apr-19 Synaptic Transmission

Synaptic Transmission Functional Anatomy Considerable variations in structure The ends of pre synaptic axons Enlarged to form synaptic knobs (terminal bouttons, end bulb) Within the end bulbs Synaptic vesicles with transmitter Mitochondria 19-Apr-19 Synaptic Transmission

Synaptic Transmission Functional Anatomy Each synaptic terminal is separated from postsynaptic structure by synaptic cleft (20–40 nm) On post synaptic membrane Many receptors for the transmitter 19-Apr-19 Synaptic Transmission

Synaptic Transmission Neurotransmitter Vesicles Voltage gated Ca++ channels Ca++ Ca++ Ca++ Pre synaptic membrane Ca++ Post synaptic membrane Synaptic cleft Na+ Receptors on postsynaptic membrane Na+ 19-Apr-19 Synaptic Transmission

Synaptic Transmission Synaptic Endings Axo-axonal Axo-dentritic Axo-somatic 19-Apr-19 Synaptic Transmission

Synaptic Transmission Chemical Synapses Transmission at most synapses is chemical Impulses in pre-synaptic axon causes release of chemical neurotransmitter Chemical transmitter binds to receptors on post synaptic membrane 19-Apr-19 Synaptic Transmission

Synaptic Transmission Chemical Synapses Triggers opening or closing of ionic channels on post synaptic neuron leads to: Excitation Inhibition Modification of sensitivity 19-Apr-19 Synaptic Transmission

Synaptic Transmission Electrical Synapses At some synapses Impulse transmission is by electrical means The membrane of Pre-synaptic Post-synaptic neurons Come closer together 19-Apr-19 Synaptic Transmission

Synaptic Transmission Electrical Synapses Gap junctions form between the cells These form low resistance bridges where ions pass with relative ease Found in Lateral vestibular nucleus Smooth muscle fibres Cardiac muscle cells 19-Apr-19 Synaptic Transmission

Synaptic Transmission Excitatory Synapse Arrival of AP at pre-synaptic nerve terminal Opening of Ca++ channels Ca++ enter the nerve terminal Release of neurotransmitter into synaptic cleft AP Ca++ Ca++ Na+ Na+ AP Threshold 19-Apr-19 RMP Synaptic Transmission EPSP

Synaptic Transmission Excitatory Synapse Neurotransmitter diffuses Binds on receptors on post synaptic membrane Opening of ionic gates (Na+, K+) AP Ca++ Ca++ Na+ Na+ AP Threshold 19-Apr-19 RMP Synaptic Transmission EPSP

Synaptic Transmission Excitatory Synapse Entry of Na+ into post synaptic cell Local depolarization (excitatory postsynaptic potential; EPSP) Conducted AP if threshold is attained Ca++ Ca++ Na+ Na+ AP Threshold 19-Apr-19 RMP Synaptic Transmission EPSP

Synaptic Transmission Temporal Summation Excitation of single pre synaptic terminal Is not enough to excite post synaptic cell Single EPSP is about 0.5 to 1 mv EPSP AP 19-Apr-19 Synaptic Transmission

Synaptic Transmission Temporal Summation You require about 10 to 20 mv change to reach threshold for conducted AP If you have a neuron firing repetitively in close succession EPSP AP 19-Apr-19 Synaptic Transmission

Synaptic Transmission Temporal Summation It is possible to have EPSP summate Reach threshold value for the post synaptic neuron to fire an AP This is temporal summation EPSP AP 19-Apr-19 Synaptic Transmission

Synaptic Transmission Spatial Summation If you have a group of neurons Firing one after another in close succession EPSP summate and can reach threshold value 2 1 3 AP AP Threshold 19-Apr-19 RMP Synaptic Transmission 1 2 3

Synaptic Transmission Spatial Summation Resulting into postsynaptic neuron firing AP This is known as Spatial Summation 2 1 3 AP AP Threshold 19-Apr-19 RMP Synaptic Transmission 1 2 3

Synaptic Transmission Inhibitory Synapse Two types of synaptic inhibition Post synaptic inhibition Pre synaptic inhibition 19-Apr-19 Synaptic Transmission

Post Synaptic Inhibition Events that occur Are similar to those at excitatory synapse except Influx of Ca++ in axon terminal Leads to release of an Inhibitory transmitter Ca++ K+ Ca++ Cl- Cl- K+ Threshold - 45mv -70mv RMP -85mv 19-Apr-19 Synaptic Transmission IPSP Hyper-polarization

Post Synaptic Inhibition Opens K+, Cl- channels K+ Move out of postsynaptic cell While Cl- move into the post synaptic cell Ca++ K+ Ca++ Cl- Cl- K+ Threshold - 45mv -70mv RMP -85mv 19-Apr-19 Synaptic Transmission IPSP Hyper-polarization

Post Synaptic Inhibition Leads to hyper polarization (IPSP) This drives the membrane potential away from threshold Making it difficult to excite post synaptic cell Ca++ K+ Ca++ Cl- Cl- K+ Threshold - 45mv -70mv RMP -85mv 19-Apr-19 Synaptic Transmission IPSP Hyper-polarization

Pre Synaptic Inhibition Excitatory cell Inhibitory cell The inhibitory neuron axon Terminate on the axon of the excitatory neuron Transmitter causing partial depolarization Excitatory transmitter Post synaptic cell 19-Apr-19 Synaptic Transmission

Pre Synaptic Inhibition Excitatory cell Inhibitory cell The inhibitory neuron axon terminal release a Transmitter that depresses the voltage of AP on excitatory neuron Partial depolarization Transmitter causing partial depolarization Excitatory transmitter Post synaptic cell 19-Apr-19 Synaptic Transmission

Pre Synaptic Inhibition Excitatory cell Inhibitory cell This reduces The amount of neurotransmitter released by the excitatory neuron Causing inhibition of The post synaptic neuron Transmitter causing partial depolarization Excitatory transmitter Post synaptic cell 19-Apr-19 Synaptic Transmission

Synaptic Transmission Neurotransmitters Excitatory Acetylcholine Noradrenalin, Adrenalin Glutamate, Aspartate Inhibitory GABA (gamma amino butyric acid) Glycine, Histamine 19-Apr-19 Synaptic Transmission

Synaptic Transmission Neuromuscular Junction (NMJ) Single motor neuron Myelin Synaptic buttons End - plate Axon 2 m Each nerve terminal has ~ 300,000 small synaptic vesicles Dense bar active zone Actylcholine receptors (nicotinic) 10,000 m2 voltage - gated channels (permeable to both Na+ and K+) Synaptic cleft Junctional fold 19-Apr-19 Synaptic Transmission

Neuromuscular Transmission Junction between nerve and muscle Muscle membrane that lie directly under the axon terminal Is known as end plate (postsynaptic membrane) Axon terminal Sarcolema Motor end plate 19-Apr-19 Synaptic Transmission

Synaptic Transmission NMJ Transmission The axon terminal of the motor neuron Contain vesicles like those found at nerve to nerve synaptic junctions 19-Apr-19 Synaptic Transmission

Synaptic Transmission Neurotransmitter Vesicles Voltage gated Ca++ channels Ca++ Ca++ Ca++ Pre synaptic membrane Ca++ Post synaptic membrane Synaptic cleft Na+ Receptors on postsynaptic membrane Na+ 19-Apr-19 Synaptic Transmission

Synaptic Transmission NMJ Transmission Arrival of AP at the axon terminal causes Depolarization of nerve plasma membrane Open voltage –sensitive Ca++ channel Ca++ diffuse into axon terminal Ca++ triggers release of Acetylcholine (Ach) into synaptic cleft 19-Apr-19 Synaptic Transmission

Synaptic Transmission NMJ Transmission Ach binds to receptors on postsynaptic membrane Opening of ionic channels (Na+, K+) Na+ moves in more than K+ move out Produces local depolarization Endplate potential (EPP) [cf EPSP] 19-Apr-19 Synaptic Transmission

Synaptic Transmission NMJ Transmission The magnitude of this EPP Much larger than the EPSP Larger amount of transmitter released Cause much more channels to open Hence an EPP from one AP is sufficient to cause AP to develop on the postsynaptic membrane In actual fact EPP elicited by one nerve AP is larger than that required to to elicit muscle AP 19-Apr-19 Synaptic Transmission

Synaptic Transmission Break Down of Ach At the endplate there is also present Acetylcholinesterase Enzyme responsible for the breakdown of Acetylcholine to choline & acetate This causes the closure of the ionic channels to enable normal repolarization of post synaptic membrane 19-Apr-19 Synaptic Transmission

Interruption of NMJ Transmission Several substances can interfere with NMJ transmission Curare Binds strongly to Ach receptor Does not open ionic channels Is not destroyed by acetylcholinesterase Hence no EPP Muscle paralysis Curare is also used during anaesthesia Cause muscle relaxation during surgery 19-Apr-19 Synaptic Transmission

Interruption of NMJ Transmission Inhibition of acetylcholinesterase Organophosphates Part of pesiticides & nerve gas Initial binding of Ach on the receptor is not inactivated Muscle is held In a permanent depolarized state Cannot initiate another AP 19-Apr-19 Synaptic Transmission

Interruption of NMJ Transmission Bacterial toxins Clostridia botulinum bacteria Botulism Prevent release of ach from the axon terminal Prevent transmission 19-Apr-19 Synaptic Transmission

Synaptic Transmission Myasthenia Gravis Condition characterized by muscle weakness Can be serious depending on the severity Due to development of antibodies against Ach receptors which become destroyed 19-Apr-19 Synaptic Transmission