Axo-axonic synapse
Axo-axonic synapses are found throughout the central nervous system, including in the hippocampus, cerebral cortex and striatum in mammals;[3][4][5] in the neuro-muscular junctions in crustaceans;[6][7] and in the visual circuitry in dipterans.
Neurons receive inputs mainly through dendrites, which play a role in spatio-temporal computation, leading to the firing of an action potential which subsequently travels to synaptic terminals passing through axons.
In axo-dendritic synapses, the presynaptic activity will affect the spatio-temporal computation in postsynaptic neurons by altering electrical potential in the dendritic branch.
Whereas the axo-somatic synapse will affect the probability of firing an action potential in the postsynaptic neuron by causing inhibitory or excitatory effects directly at the cell body.
Thus, the axo-axonic synapse will mainly affect the probability of neurotransmitter vesicle release in response to an action potential firing in the postsynaptic neuron.
Within the next two years, scientists found axo-axonic synapses in various other places in the nervous system in different animals, such as in the retina of cats and pigeons,[16] in the lateral geniculate nucleus of monkeys,[17] in the olfactory bulb of mice,[18] and in various lobes in the octopus brain.
Prior to the discovery of axo-axonic synapses, physiologists predicted the possibility of such mechanisms as early as in year 1935, following their observations of electrophysiological recordings and quantal analysis of brain segments.
At that time, this phenomenon was known as “presynaptic inhibitory action”, the term proposed by Karl Frank in 1959 [14] and later well summarized by John Eccles in his book.
They found that GABAergic neurons project onto the axons of pyramidal cells in the cerebral cortex to form axo-axonic synapse and elicit excitatory effects in cortical microcircuits.
The axo-axonic synapse in the cerebellar cortex originally appeared in one of the drawings of Santiago Ramón y Cajal in his book published in 1909.
[4] In the striate cortex, as the Golgi's method and electron microscopy revealed, as many as five axo-axonic synapses are formed onto a single pyramidal cell.
[31] The horizontal interneurons show a laminar distribution of dendrites and are involved in axo-axonic synapses in the hippocampus, which get direct synaptic inputs from CA1 pyramidal cells.
These axo-axonic synapses are formed by dopaminergic inhibitory interneurons (on the presynaptic side) projecting onto the axons of glutamatergic cortico-striatal fibers in the rat striatum.
[34] Electron microscopy studies on the kitten brainstem quantified synaptogenesis of axo-axonic synapses in the spinal trigeminal nucleus at different development ages of the brain.
The highest rate of synaptogenesis is during the first 3 to 6 days, at the end of which, the kitten's spinal trigeminal nucleus will have nearly half of the axo-axonic synapses present in adult cats.
Axo-axonic synapses are formed on baroreceptor terminals by the presynaptic adrenergic fibers, and are proposed to play a role in baroreflex.
[42] Interestingly, the authors claimed that axo-axonic synapses, which are abundant in rats, are absent in the lateral vestibular nucleus in cats.
Subsequent studies found that axo-axonic synapses showed varying numbers of occurrence based on the location of the leg muscles from the nervous system.
[7] An example of the physiological role of axo-axonic synapses, which are formed by GABAergic inhibitory interneurons to the axons of granule cells, is in eliciting spontaneous seizures, which is a key symptom of Intractable Epilepsy.
A study on the spinal cord in mice suggests that the sensory Ig/Caspr4 complex is involved in the formation of axo-axonic synapses on proprioceptive afferents.
