Synapse and synaptic transmission

Synapse and synaptic transmission

Neurons communicate by electrical or chemical signaling. In electrical synapses (Gap Junctions), the neuronal membrane is continuous with another neuron leading to rapid and synchronous activity. However, most neurons in the CNS communicate by chemical signaling mediated via specialized molecules called the neurotransmitters. Unlike electrical synapses, the neuronal membrane in the chemical synapse is discontinuous. The region formed between the pre, and post synaptic neuron is known as synapse with the space in between termed ‘synaptic cleft’. Presynaptic neurons release neurotransmitter to the synaptic cleft where it diffuses and bind to the receptors present at the pre and postsynaptic sites to exert its effect

Synapse

   Neurotransmitters 

Various neurotransmitters in CNS and PNS include amino acids, amino acid derivatives, small peptides, hormones, etc.  Neurotransmitters are broadly classified into two types depending on their function. The neurotransmitters that can evoke a response by activating their receptors on the postsynaptic cell are known as excitatory neurotransmitters and the ones that inhibit the transmission is termed as an inhibitory neurotransmitter. Glutamate is the major excitatory and GABA is the major inhibitory neurotransmitter in the CNS. However, there are hundreds of other neurotransmitters in the CNS contributing to the diverse signaling of neurons .

  Mechanism of neurotransmitter release

Activation of receptors on the membrane of an afferent neurons leads to influx of ions generating a receptor potential/generator potential. Depolarization of the membrane due the influx of positively charged ions beyond the threshold trigger the opening of Na+ channels at the vicinity of axon hillock. This evoke a transient positive charge known as the action potential.  Axon potential travel down the axon at a constant speed which is further enhanced by the insulation. Nodes of Ranvier are the intermittent uninsulated spots on an axon where the axon potential is regenerated [see Figure]. Action potential reaching the terminals divides and move further to presynaptic terminals. Activation of the voltage gated Ca2+ channels (VGCC) at the presynaptic terminals leads to an influx of Ca2+. This transient rise in the Ca2+ levels promote their binding with synaptotagmins. Ca2+ bound synaptotagmins along with soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) trigger the fusion and release of docked synaptic vesicles (Svs) containing neurotransmitters into the synaptic cleft [see Figure]. .

Binding of neurotransmitter evoke response in the postsynaptic neurons by activating two major types of receptors: ionotropic (ion channels) and/or metabotropic (G-protein coupled) receptors. Depending on the nature of neurotransmitters, activation of the receptor drive opening or closing of the channels. Excess neurotransmitters in the synaptic cleft are cleared by astrocytes, reuptake by neurons or degraded at the synapses [see Figure]. The neurotransmitter in the glia gets converted or degraded to an inactive form and is transported back to the presynaptic terminal through the receptors [see Figure]. The degradation products are recycled to generate functional neurotransmitters . 

Types of Neuronal transmission

   Inhibitory neurotransmission

The major inhibitory neurotransmitter in the CNS is GABA (g-aminobutyric acid). The postsynaptic GABA receptors are classified into three types GABAAR GABABR and GABACR. GABAA and GABAare ionotropic receptors whereas GABABR relay on metabotropic signaling. Binding of GABA to the postsynaptic GABAand GABACreceptors leads to the opening of the channel and the influx of negatively charged Cl ions into the cytosol. This hyper-polarizes the postsynaptic membrane and prevent the generation of action potentials. 

GABABR on the other hand, exerts its action on the postsynaptic membrane by activating K+ channels and subsequent efflux of ions or alternatively by inhibiting Ca2+ channels in presynaptic membrane. The net potential generated due to the flow of negatively charged ions are known inhibitory postsynaptic potential (IPSPs) or inhibitory post synaptic currents (IPSCs).

  Excitatory neurotransmission

The predominant excitatory transmitter in the mammalian CNS is glutamate. Release of glutamate from the presynaptic neuron activates pre-and postsynaptic receptors. Like GABA, glutamate can also signal via ionotropic and metabotropic receptors. Activation of ionotropic glutamate receptors induce influx of monovalent and/or divalent cations through the channel (ionotropic). The resulting influx of ions recorded in voltage-clamp electrophysiology (keeping the voltage constant) is observed as excitatory post synaptic currents (EPSCs) and in current clamp (keeping the current constant) is excitatory post synaptic potential (EPSPs). Depolarization of the postsynaptic membrane trigger the generation of action potentials thereby facilitating information transfer to adjacent neuron/effector organ.

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