Below are the brain locations where axo-axonic synapses are found in different animals.
Cerebellar cortex 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. Later using
electron microscopy, it was confirmed that the
basket cell axon projects on the
axon hillock of
Purkinje cells in the cerebellar cortex in cats and other mammals, forming axo-axonic synapses. Network-level study revealed that the
granule cells which, through their parallel fibers, activate Purkinje cells, also activate the basket cells, which subsequently inhibit the effect of Purkinje cells on the downstream network.
Cerebral cortex Axo-axonic synapses are found In the
visual cortex (in V1 and V2) in mammals, and have been well studied in cats, rats and primates such as monkeys. The synapse is formed on the initial segments of the axons of pyramidal cells in several layers in the visual cortex. The projecting neurons for these synapses come from various parts of the
central nervous system and
neocortex. Similarly, axo-axonic synapses are found in the
motor cortex, in the
subiculum and in the
piriform cortex. Studying the locations of axo-axonic synapses in the primary olfactory cortex, researchers have suggested that axo-axonic synapses may play a critical role in synchronizing
oscillations in the piriform cortex (in the olfactory cortex), which aids
olfaction. The axo-axonic synapses are also found in the
hippocampus. These synapses are found to be formed mainly on principal cells in
stratum oriens and stratum pyramidale and rarely on stratum radiatum; they commonly receive projections from
GABAergic local
interneurons. 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. In this study, authors examined 4,811 synapses in rat striatum sections, and 15 of them were found to be the axo-axonic synapses. 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. 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. Authors identified the synapses by counting
vesicles released in the
synaptic cleft, which can be observed in the
micrographs. Axo-axonic contacts are shown to consistently increase throughout the development period, starting from the age of 3 hours to the age of 27 days in kittens. 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. Later, between 16 and 27 days of age, there is another surge of axo-axonic synaptogenesis.
Spinal Cord Axo-axonic synapses are found in the mammalian
spinal reflex arc and in
Substantia gelatinosa of Rolando (SGR). In the spinal cord, axo-axonic synapses are formed on the terminals of sensory neurons with presynaptic inhibitory interneurons. These synapses are first studied using
intracellular recordings from the spinal motoneurons in cats, and have been shown to cause presynaptic inhibition. This seems to be a common mechanism in spinal cords, in which
GABAergic interneurons inhibit presynaptic activity in sensory neurons and eventually control activity in motor neurons enabling selective control of muscles. In efforts to quantify the occurrence of axo-axonic synapses in the SGR region in rats, 54 such synapses were found among the total 6,045 synapses examined. These 54 axo-axonic synapses were shown to have either agranular vesicles or large granular vesicles. Interestingly, the authors claimed that axo-axonic synapses, which are abundant in rats, are absent in the lateral vestibular nucleus in cats. The
axon hillock and initial axon segments of mauthner cells receive terminals from extremely fine
unmyelinated fibers, which cover the axon hillock with helical projections. These helical projections around mauthner cells are also known as the axon cap. The difference between the axo-axonic synapses and other synapses on mauthner cells is that synapses on dendrites and soma receive myelinated fibers, while axons receive unmyelinated fibers.
Neuromuscular junction Inhibitory axo-axonic synapses are found in the
crustacean neuromuscular junctions and have been widely studied in Crayfish. Axo-axonic synapses are formed on the excitatory axons as a postsynaptic neuron by the motor neurons from the presynaptic side. Motor neurons, which is the common inhibitor in crab limb closers and limb accessory flexors, form axo-axonic synapses in addition to the
neuromuscular junction with the muscles in crayfish. These synapses were first observed in 1967, when they were found to cause presynaptic inhibition in leg muscles of crayfish and crabs. Subsequent studies found that axo-axonic synapses showed varying numbers of occurrence based on the location of the leg muscles from the nervous system. For instance, proximal regions have thrice as many axo-axonic synapses than the central regions. These synapses are proposed to function by limiting
neurotransmitter release for controlled leg movements. == Clinical Significance ==