An interneuron (also called relay neuron,association neuron or bipolar neuron) is a term used to describe a neuron which has two different common meanings.

In the peripheral nervous system (PNS), an interneuron is a neuron that communicates only to other neurons. Interneurons are the neurons that provide connections between sensory and motor neurons, as well as between themselves. Contrast to sensory neurons or motor neurons, which respectively provide input from and output to the rest of the body. Interneurons are found in the grey matter. One type of peripheral interneuron is the Renshaw cell.

According to the PNS definition, the neurons of the central nervous system, including the brain, are all interneurons. However, in the CNS, the term interneurons is also used for the general group of small, locally projecting neurons of the central nervous system. These neurons are typically inhibitory, and use the neurotransmitter GABA. However, excitatory interneurons also exist.

One example of interneurons are inhibitory interneurons in the neocortex which selectively inhibit sections of the thalamus based on synaptic input both from other parts of the neocortex and from the thalamus itself. This is theorized to help focus higher attention on relevant sensory input and help block out behavioraly irrelevant or unchanging input, such as the sensation of the backs of your thighs on a chair. A human brain contains about 100 billion interneurons.

Calbindin

• interneuron marker. PMID: 15557103
• Major cortical interneuron subclasses can be identified based on expression of distinct calcium-binding proteins including parvalbumin, calretinin, or calbindin. PMID: 17245711, PMID: 17106195
• labeled several classes of interneuron in SC. In the upper CaBP tier, the labeled neurons were all small, but they varied in morphology and included horizontal, pyriform, and stellate neurons. A unique class of interneuron was labeled by anti-CaBP in the OL-IGL tier. This cell was stellate-like with highly varicose dendrites and broad dendritic trees. Other labeled neurons in the intermediate and deep tiers included nonvaricose stellate neurons and rare large neurons in the DGL. PMID: 1713236

Calretinin (CR)

• an interneuron marker. PMID: 15557103
• Major cortical interneuron subclasses can be identified based on expression of distinct calcium-binding proteins including parvalbumin, calretinin, or calbindin. PMID: 17245711, PMID: 17106195
• marker that can be used to classify cortical interneurons. PMID: 17376969
• an average of 56% of the calretinin-positive neurons in the monkey entorhinal cortex contained GABA, whereas about 27% of the GABA-positive neurons co-expressed calretinin. PMID: 15301438
• In all mammalian species so far examined, the vestibulocerebellum is enriched of unipolar brush cells (UBCs) (a type of glutamatergic interneuron in the granular layer of the cerebellum) that are strongly immunoreactive for the calcium binding protein calretinin (CR) in both the somatodendritic and axonal compartment. PMID: 12209836
• Two types of calretinin-immunostained terminals were found in the CA1 region: one of them presumably derived from the thalamic reuniens nucleus, and established asymmetric synapses on dendrites and spines. The other type originating from local interneurons formed symmetric synapses on both pyramidal and interneuron dendrites. PMID: 12064772
• a marker that differentially labels neurons in the central nervous system. finding of calretinin-immunoreactive axon terminals with asymmetrical synapses suggests that the second class of calretinin neuron is a novel type of a (presumably excitatory) interneuron. PMID: 10954838
• a useful marker for AII amacrine cells (a critical interneuron in the rod pathway of mammalian retinae) in the rabbit retina. PMID: 10404104

Catecholamine

• GABA and a catecholamine (probably dopamine) are colocalized in a limited number of interneurons within the central pattern generator circuits that control feeding-related behaviors in Aplysia. PMID: 11891652

CB1 (type 1 cannabinoid receptor)

• prenatal CB(1)R activity governs proper interneuron placement and integration during corticogenesis. Moreover, eCBs use TrkB receptor-dependent signaling pathways to regulate subtype-selective interneuron migration and specification. PMID: 16357196
• Membrane staining for CB1 was only found in axon terminals, all of which contained GABA and formed symmetric synapses. Double immunostaining also revealed that CB1-positive cells formed two neurochemically distinct subpopulations: two-thirds were cholecystokinin positive and one-third expressed calbindin, each subserving specific inhibitory functions in cortical networks. PMID: 16033894
• most parvalbumin immunoreactive interneurons (86.5%), more than one-third (39.2%) of cholinergic interneurons, and about one-third (30.4%) of the NOS-positive neurons are labeled for CB(1). Calretinin-immunolabeled neurons were devoid of CB(1). PMID: 15236348
• cannabinoid receptors are located on inhibitory, but not excitatory, axon terminals impinging upon hippocampal interneurons, and that CA1 pyramidal neurons, and not interneurons, are capable of generating endogenous cannabinoids during prolonged states of depolarization. PMID: 12911748

CCKpan> (Cholecystokinin)

• cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. PMID: 16158066
• Postnatal development and migration of cholecystokinin-immunoreactive interneurons in rat hippocampus. PMID: 12927199
• found co-localized with the inhibitory neurotransmitter GABA in interneurons of the hippocampus. PMID: 9185537
• a marker for perisomatic inhibitory cells. PMID: 9034894

ChAT (choline acetyl-transferase)

• a striatal interneuron marker. PMID: 15236348
• a marker for cholinergic interneurons. PMID: 10486177
• the enzyme catalyzing the biosynthesis of acetylcholine and is considered to be a phenotypically specific marker for cholinergic neurons, and acetylcholine may be a neurotransmitter in the larval photoreceptor cells as well as in a first-order interneuron in the larval visual system of Drosophila melanogaster. PMID: 8565051

Chx10

• one of the earliest markers of the developing retina. It is required for retinal progenitor cell proliferation as well as formation of bipolar cells, a type of retinal interneuron. PMID: 15459106
• a gene normally restricted to a class of ventral interneurons. PMID: 10482235

DLX

• an interneuron marker. PMID: 17182777
• expressed in a subset of cortical and hippocampal interneurons, is essential during embryonic development for the production of forebrain GABAergic interneurons and is also required for regulating the functional longevity of cortical and hippocampal interneurons in the adult brain. PMID: 16007083

EN1 (pan>Engrailed-1, EN-EN-1)

• specific for distinct classes of interneurons. PMID: 16508308
• could be involved in interneuron-motoneuron connectivity but that its expression is not restricted to a distinct functional subclass of ventral interneuron. PMID: 11068006
• regulate axon pathfinding by association interneurons that project to motor neurons. PMID: 10477289

ER81

• olfactory bulb interneuron marker. PMID: 12890509, PMID: 12514213

EVX1

• Specific distinct classes of interneurons. PMID: 16508308
• a postmitotic determinant of V0 interneuron identity and reveal a critical postmitotic phase for neuronal determination in the developing spinal cord. PMID: 11239430

GABA

• an interneuron marker. PMID: 12967924
• GABAA receptor expression in some but not all interneuron populations. PMID: 15379895
• GABA(B) receptor 1-like immunoreactivity (GBR1-LI) was most intense in presumed GABAergic interneurons of all hippocampal subregions. PMID: 10587087

GAD65 (glutamic acid decarboxylase 65)

• a marker of interneurons. PMID: 12657704, PMID: 15872114

GAD67 (glutamic acid decarboxylase 67)

• a general marker for most inhibitory interneurons. PMID: 14519496

GATA

• GATA proteins identify a novel ventral interneuron subclass in the developing chick spinal cord. PMID: 12217316

GluR-B

• a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in gamma-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. PMID: 11248119

ISL1 (pan>IslIslet1)

• required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons. PMID: 8565076

Lhx1 and Lhx5

• co-expressed in multiple interneuron cell types in the developing spinal cord. PMID: 17166926

Lhx3

• involved in the generation of two adjacent, but distinct, cell types for locomotion, motor neurons and V2 interneurons. PMID: 12150931

Lhx6

• a gene induced in the medial ganglionic eminence and maintained in parvalbumin- and somatostatin-positive interneurons, is required for the specification of these neuronal subtypes in the neocortex and the hippocampus. We also show that Lhx6 activity is required for the normal tangential and radial migration of GABAergic interneurons in the cortex. PMID: 17376969

mGluR1alpha

• found almost exclusively in interneurons in rodent cortex, but expressed in primate brain pyramidal cells. PMID: 14624486

Neuropeptide Y (NPY)

• characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS)-containing interneurons in stratum oriensalveus. PMID: 15098725

MOR (mu opioid receptor)

• most frequently on interneurons specialized to inhibit granule cell output, and are on a limited number of interneurons that inhibit granule cell distal dendrites. PMID: 16716508

Neuropeptide Y

• an marker for interneurons. PMID: 15869748, PMID: 12957498, PMID: 1542411, PMID: 6149547

Nkx2-2 (Nkx2.2)

• interneuron progenitor marker. PMID: 16508308, PMID: 15548668, PMID: 12874134, PMID: 10217145
• necessary and sufficient for the development of V3 interneurons. PMID: 11566099

NMDAR2D

• Expressed in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus. PMID: 8915584

NOS (pan>nitnitric oxide synthase)

• a marker of striatal interneurons. PMID: 17177262, PMID: 15548548, PMID: 15236348, PMID: 12000114
• the NOS-containing interneurons were under direct control of SP-containing projection neurons in the striatum. PMID: 11585579

Parvalbumin (PV)

• Major cortical interneuron subclasses can be identified based on expression of distinct calcium-binding proteins including parvalbumin, calretinin, or calbindin. PMID: 17245711, PMID: 17106195
• a marker of one population of striatal interneurons. PMID: 7823186
• the striatal interneuron marker. PMID: 15236348
• immunoreactivity can therefore be used as a reliable marker for chandelier cell (a well-characterized morphological type of gamma-aminobutyric acid-releasing cortical interneuron) axons. PMID: 2648389

Pax2

• expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development. PMID: 9409667

SDF-1 (stromal cell-derived factor-1)

• expressed in the main invasion route for cortical interneurons in the SVZ/IZ. PMID: 17182777
• a potent chemoattractant for isolated striatal precursors. PMID: 12832536

Somatostatin

• a more specific marker for a subpopulation of interneurons. PMID: 17376969, PMID: 15269966, PMID: 2567743, PMID: 1702191, PMID: 7951690
• immunoreactivity occurs in a specific subgroup of cholinergic descending interneurons in the myenteric plexus of the guinea-pig small intestine. PMID: 9799437

SPO

• differentially expressed by various interneuron subpopulations in the hippocampus of C57Bl/6 mice. PMID: 12271488

Substance P Receptor (SPR)

• expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. PMID: 17097238

VIP (Vasoactive intestinal polypeptide)

• has been shown to be present in a morphologically heterogeneous subpopulation of interneurons in the dentate gyrus. PMID: 8758949
• the galanin- and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via a cholinergic interneuron. PMID: 1375382