Interneurons are a type of nerve cell that connects motor neurons with sensory neurons . Their axons and dendrites project into a single brain region, unlike most cells of the nervous system, which tend to have axonal projections in more distant regions. As we will see throughout the article, interneurons act as inhibitory neurons through the neurotransmitter GABA

We will now explain in more detail what these nerve cells are, what their main characteristics are and what functions they perform.

Interneuron: definition and characteristics

An interneurone is a type of nerve cell that is usually located in integrative areas of the central nervous system , whose axons (and dendrites) are limited to a single brain area. This characteristic distinguishes them from the main cells, which often have axonal projections outside the area of the brain where their cell bodies and dendrites are located.

Major neurons and their networks underlie local information processing and storage and represent the main sources of information output from any brain region, while interneurons, by definition, have local axons that manage overall neuronal activity.

While the major cells are mostly excitatory, when using glutamate as a neurotransmitter, interneurons often use gamma-aminobutyric acid (GABA) to inhibit their targets . Since GABA acts mainly through the opening of ion channels in the post-synaptic neuron, interneurons achieve their functional effects by hyperpolarising large groups of major cells (although, in some circumstances, they may also mediate depolarisation).

Interneurons in the spinal cord may use glycine, along with GABA, to inhibit the major cells, while interneurons in the cortical areas or basal ganglia may release various neuropeptides (cholecystokinin, somatostatin, encephalins, etc.) in addition to GABA. In some regions, such as the basal ganglia and cerebellum, the main neurons are also gabaergic.

Types

Most interneurons innervate different types of target cells (both master cells and interneurons) in roughly proportion to their appearance in the neuropyl (the region between various cell bodies or somas of neurons in the grey matter of the brain and spinal cord), and therefore make synapses predominantly in the most abundant cell type, which are the local master cells .

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Below are the two main types of cortical interneurons: perisomatic and dendritic inhibitory cells.

1. Perisomatic inhibitory cells

The precise site of termination, as well as the specific entry characteristics allow this cell group to be dissected into two main types of interneurons : axon or spider cells, which innervate exclusively the initial axon segments of the main cells and are produced in both the hippocampus and the neocortex; and basket cells, which form multiple synaptic contacts in the somas and the proximal dendrites of the main cells.

Due to the strategic location of their axon terminals, it has been suggested that axon cells simultaneously inhibit the production of large populations of major cells. However, recent evidence suggests that their effect mediated by the post-synaptic GABAA receptor may be depolarizing and, as a consequence, may discharge the entire population of pyramidal cells that they innervate, with the aim of synchronizing their production or reestablishing conductance in their dendritic trees.

Basket cells are present in many different areas of the brain, including the cerebral cortex and cerebellum a (in the cerebellum, they inhibit Purkinje cells). In the neocortex and the hippocampus, several subtypes of basket cells have been distinguished. The two main subtypes of hippocampal basket cells can be most easily distinguished based on their content of neuropeptide-binding proteins and calcium.

2. Dendritic inhibitory cells

This group of interneurons is the most diverse, both morphologically and functionally . Dendritic inhibitory cells are present in many different parts of the nervous system, including the cerebellum, the olfactory bulb and all areas of the cerebral cortex. In fact, a wide variety of dendritic inhibitory interneurons have been described in the neocortex.

These types of interneurons include Martinotti cells, which primarily target the apical plume region of pyramidal cells and contain the neuropeptide somatostatin; double-bouquet cells; and bipolar cells, which primarily target basal dendrites. However, the precise functions of these neocortical cell types have been difficult to identify.

Different types of dendritic interneurons have evolved to control glutamatergic inputs to the major cells from different sources. Importantly, individual dendritic inhibitory cells of any type provide from 2 to 20 synapses in a single target pyramidal cell, which are scattered throughout the dendritic tree.

Functions of cortical interneurons

What has been found so far is that interneurons regulate the levels of physiological activity in the brain , preventing runaway excitation in recurrent cortical networks. A similar role in stabilizing cortical network dynamics has also been attributed to inhibition of Renshaw cell-mediated feedback in the motor regions of the spinal cord.

There is evidence that lasting changes in the level of excitation are accompanied by a corresponding change in the general level of inhibition; however, transient imbalances between excitation and inhibition may also be induced. In the hippocampus and neocortex, changes in the level of interneuronal firing have been observed to accompany novel experiences relevant to behaviour, and probably contribute to enabling the plastic changes induced by such learning events.

Interneurons make a critical contribution to the generation of network oscillations and synchronize the activity of the main cells during oscillatory and transient brain states. Perisomatic interneurons in particular are considered indispensable for the generation of gamma rhythms (involved in conscious perception), although the exact nature of their contribution may vary between different regions.

Due to the strategic location of their axon terminals, it has been suggested that axon cells simultaneously inhibit the production of large populations of major cells. However, recent evidence suggests that their effect mediated by the post-synaptic GABAA receptor may be depolarizing and, as a consequence, may discharge the entire population of pyramidal cells that they innervate, with the aim of synchronizing their production or reestablishing conductance in their dendritic trees.

Basket cells are present in many different areas of the brain, including the cerebral cortex and cerebellum a (in the cerebellum, they inhibit Purkinje cells).
In the neocortex and the hippocampus, several subtypes of basket cells have been distinguished. The two main subtypes of hippocampal basket cells can be most easily distinguished based on their content of neuropeptide-binding proteins and calcium.

2. Dendritic inhibitory cells

This group of interneurons is the most diverse, both morphologically and functionally .
Dendritic inhibitory cells are present in many different parts of the nervous system, including the cerebellum, the olfactory bulb and all areas of the cerebral cortex. In fact, a wide variety of dendritic inhibitory interneurons have been described in the neocortex.

These types of interneurons include Martinotti cells, which primarily target the apical plume region of pyramidal cells and contain the neuropeptide somatostatin; double-bouquet cells; and bipolar cells, which primarily target basal dendrites.
However, the precise functions of these neocortical cell types have been difficult to identify.

Different types of dendritic interneurons have evolved to control glutamatergic inputs to the major cells from different sources. Importantly, individual dendritic inhibitory cells of any type provide from 2 to 20 synapses in a single target pyramidal cell, which are scattered throughout the dendritic tree.

Functions of cortical interneurons

What has been found so far is that interneurons regulate the levels of physiological activity in the brain , preventing runaway excitation in recurrent cortical networks. A similar role in stabilizing cortical network dynamics has also been attributed to inhibition of Renshaw cell-mediated feedback in the motor regions of the spinal cord.