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 gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...

nucleus which functions as a "master brake" for the midbrain dopamine system. This region was discovered by the researchers, M. Barrot, J.Kaufling and T. Jhou. 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 th ...

(VTA) and possesses robust functional and structural links to the dopamine pathways. Notably, both acute and chronic exposure to

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

s 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: FOS, F ...

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. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA ...

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 cin ...

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 the ...

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 cogni ...

* Lateral habenula *

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

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 ...

* Dorsal raphe *

Laterodorsal tegmental nucleus The laterodorsal tegmental nucleus (or lateroposterior tegmental nucleus) is a nucleus situated in the brainstem, spanning the midbrain tegmentum and the pontine tegmentum. Its location is one-third of the way from the pedunculopontine nucleus to t ...

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 a ...

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 hypo ...

Pontine tegmentum The pontine tegmentum, or dorsal pons, is the dorsal part of the pons located within the brainstem. The ventral part or ventral pons is known as the basilar part of the pons, or basilar pons. Along with the dorsal surface of the medulla oblonga ...

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 ...

Outputs

GABA projections from the RMTg include: *RMTg →

Raphe nuclei The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the ...

*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, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

by endogenous opioids and

opiate An opiate is an alkaloid substance derived from opium (or poppy straw). It differs from the similar term ''opioid'' in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain ( ...

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, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...

and

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...

) excite the

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

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 use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

(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 v ...

), 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