The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a

GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...

nucleus which functions as a "master brake" for the midbrain dopamine system. It is poorly differentiated from the rest of the

ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...

(VTA) and possesses robust functional and structural links to the

dopamine pathways Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

. Notably, both acute and chronic exposure to psychostimulants have been shown to induce

FosB Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: C-Fos, ...

and

ΔFosB Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: FOS, F ...

expression in the RMTg; no other drug type has been shown to induce these proteins in the RMTg.

Inputs

The RMTg receives incoming projections from the following structures: *

Medial prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...

Cingulate cortex The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the ci ...

Preoptic area The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region, (medial, median, lateral, and periventricular). Functions The preoptic area is responsible for ther ...

Lateral hypothalamus The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognit ...

* Lateral habenula *

Superior colliculus In neuroanatomy, the superior colliculus () is a structure lying on the roof of the mammalian midbrain. In non-mammalian vertebrates, the homologous structure is known as the optic tectum, or optic lobe. The adjective form ''tectal'' is commonly ...

Periaqueductal gray The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for d ...

Dorsal raphe The dorsal raphe nucleus is located on the midline of the brainstem and is one of the raphe nuclei. It has rostral and caudal subdivisions. * The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolateral ...

* Laterodorsal tegmental nucleus *

Substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra app ...

Nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypotha ...

Pontine tegmentum Pontine may refer to: * Having to do with the pons, a structure located in the brain stem (from ''pons'', "bridge") * Pontine Marshes, a region of Italy near Rome * Pontine Islands The Pontine Islands (, also ; it, Isole Ponziane ) are an ar ...

Ventral pallidum The ventral pallidum (VP) is a structure within the basal ganglia of the brain. It is an output nucleus whose fibres project to thalamic nuclei, such as the ventral anterior nucleus, the ventral lateral nucleus, and the medial dorsal nucleus. The ...

Outputs

GABA projections from the RMTg include: *RMTg → Raphe nuclei *RMTg →

*RMTg → Lateral hypothalamus *RMTg → Substantia nigra *RMTg → VTA *RMTg → Periaqueductal gray *RMTg → Pontine tegmentum

Clinical significance

The RMTg plays a "crucial role" in the regulation of dopaminergic neuronal activity in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

endogenous opioid Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but th ...

s and

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonis ...

drugs. The GABAergic neurons that project from the RMTg to the midbrain dopaminergic nuclei (i.e., the ventral tegmental area and substantia nigra pars compacta) express

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

s. Current evidence suggests that exogenous opiates (e.g.,

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

and

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...

) excite the

dopamine pathway Dopaminergic pathways (dopamine pathways, dopaminergic projections) in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. ...

s originating in the VTA by activating the μ-opioid receptors in neurons projecting from the RMTg; opioid activation of these neurons leads to disinhibition of the GABAergic brake on dopamine networks. Since RMTg projections to the VTA are the primary inhibitor of the dopaminergic pathways that are implicated in

addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...

(e.g., the

mesolimbic pathway The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral ...

), the RMTg plays a significant role in the development of opiate addictions. Psychostimulants have been shown to increase expression of the

and

in the RMTg; the effects of stimulant-induced increases in ΔFosB expression in the RMTg are not known.

Notes

References

{{Neurotransmitter systems Midbrain