Showing papers on "Rostromedial tegmental nucleus published in 2019"
TL;DR: The ability of an aversive punisher to inhibit reward seeking depends on coordinated activity of three distinct afferents to the rostromedial tegmental nucleus (RMTg) arising from cortex, brainstem, and habenula that drive triply dissociable RMTg responses to aversive cues, outcomes, and prediction errors, respectively.
43 citations
TL;DR: In vivo electrophysiology finds that rEPN or LHb subpopulations exhibit activation/inhibition patterns after negative/positive motivational stimuli, similar to the RMTg, while temporary inactivation of a region centered on the r EPN decreases LHb basal and burst firing, and reduces valence-related signals in LHb neurons.
Abstract: Lateral habenula (LHb) neurons are activated by negative motivational stimuli and play key roles in the pathophysiology of depression. Prior reports suggested that rostral entopeduncular nucleus (rEPN) neurons drive these responses in the LHb and rostromedial tegmental nucleus (RMTg), but these influences remain untested. Using rabies viral tracers, we demonstrate disynaptic projections from the rEPN to RMTg, but not VTA, via the LHb in rats. Using in vivo electrophysiology, we find that rEPN or LHb subpopulations exhibit activation/inhibition patterns after negative/positive motivational stimuli, similar to the RMTg, while temporary inactivation of a region centered on the rEPN decreases LHb basal and burst firing, and reduces valence-related signals in LHb neurons. Additionally, excitotoxic rEPN lesions partly diminish footshock-induced cFos in the LHb and RMTg. Together, our findings indicate an important role of the rEPN, and possibly immediately adjacent hypothalamus, in driving basal activities and valence processing in LHb and RMTg neurons.
36 citations
TL;DR: RNA sequencing is used to identify genes significantly enhanced in the rat RMTg as compared to adjacent VTA, and then the detailed distribution of two genes in particular, prepronociceptin (Pnoc) and FoxP1 are examined, which show that optogenetic manipulation of R MTg in mice bidirectionally modulates real-time place preference.
Abstract: The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic structure identified in 2009 that receives strong inputs from the lateral habenula and other sources, sends dense inhibitory projections to midbrain dopamine (DA) neurons, and plays increasingly recognized roles in aversive learning, addiction, and other motivated behaviors. In general, little is known about the genetic identity of these neurons. However, recent work has identified the transcription factor FoxP1 as enhanced in the mouse RMTg (Lahti et al. in Development 143(3):516–529, 2016). Hence, in the current study, we used RNA sequencing to identify genes significantly enhanced in the rat RMTg as compared to adjacent VTA, and then examined the detailed distribution of two genes in particular, prepronociceptin (Pnoc) and FoxP1. In rats and mice, both Pnoc and FoxP1 were expressed at high levels in the RMTg and colocalized strongly with previously established RMTg markers. FoxP1 was particularly selective for RMTg neurons, as it was absent in most adjacent brain regions. We used these gene expression patterns to refine the anatomic characterization of RMTg in rats, extend this characterization to mice, and show that optogenetic manipulation of RMTg in mice bidirectionally modulates real-time place preference. Hence, RMTg neurons in both rats and mice exhibit distinct genetic profiles that correlate with their distinct connectivity and function.
33 citations
TL;DR: It is found that rostromedial tegmental nucleus neurons are broadly excited by aversive stimuli of different sensory modalities and inhibited by reward-related stimuli, which indicates a broad RMTg role in encoding aversion and driving VTA responses and behavior.
Abstract: The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has been hypothesized to be broadly activated by aversive stimuli. However, this encoding pattern has only been demonstrated for a limited number of stimuli, and the RMTg influence on ventral tegmental (VTA) responses to aversive stimuli is untested. Here, we found that RMTg neurons are broadly excited by aversive stimuli of different sensory modalities and inhibited by reward-related stimuli. These stimuli include visual, auditory, somatosensory and chemical aversive stimuli, as well as "opponent" motivational states induced by removal of sustained rewarding or aversive stimuli. These patterns are consistent with broad encoding of negative valence in a subset of RMTg neurons. We further found that valence-encoding RMTg neurons preferentially project to the DA-rich VTA versus other targets, and excitotoxic RMTg lesions greatly reduce aversive stimulus-induced inhibitions in VTA neurons, particularly putative DA neurons, while also impairing conditioned place aversion to multiple aversive stimuli. Together, our findings indicate a broad RMTg role in encoding aversion and driving VTA responses and behavior.
26 citations
TL;DR: The present results reveal that the R MTg-VTA-Acb pathway plays a crucial role in the depression-like behavior in animals undergoing alcohol withdrawal, further advocating the RMTg as a potential therapeutic target for alcoholism.
24 citations
TL;DR: Data demonstrate that the rostromedial tegmental nucleus (RMTg) plays a distinct role in the negative affective state associated with acute withdrawal and may therefore be critically involved in the neurobiological mechanisms that promote relapse during early stages of recovery.
21 citations
TL;DR: In this article, the authors investigated the role of the rostromedial tegmentum (RMTg) in the development of a maladaptive behavior in which rats repeatedly exposed to inescapable footshock, fail to avoid or escape the same stressor when subsequently given the opportunity to do so.
20 citations
TL;DR: Data show that locally-infused RMTg morphine or selective RMTG GABAergic neuron inhibition produces 87% of the maximal antinociceptive effect of systemic morphine, and RMT g GABAergic neurons modulate dopamine release in the nucleus accumbens, and these results provide compelling evidence that R MTg GABAergic cells are involved in processing of nociception information and are important mediators of opioid analgesia.
Abstract: A recently defined structure, the rostromedial tegmental nucleus (RMTg; aka tail of the ventral tegmental area [VTA]), has been proposed as an inhibitory control center for dopaminergic activity of the VTA. This region is composed of GABAergic cells that send afferent projections to the ventral midbrain and synapse onto dopaminergic cells in the VTA and substantia nigra. These cells exhibit µ-opioid receptor immunoreactivity, and in vivo, ex vivo, and optogenetic/electrophysiological approaches demonstrate that morphine excites dopamine neurons by targeting receptors on GABAergic neurons localized in the RMTg. This suggests that the RMTg may be a key modulator of opioid effects and a major brake regulating VTA dopamine systems. However, no study has directly manipulated RMTg GABAergic neurons in vivo and assessed the effect on nociception or opioid analgesia. In this study, multiplexing of GABAergic neurons in the RMTg was achieved using stimulatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and inhibitory kappa-opioid receptor DREADDs (KORD). Our data show that locally infused RMTg morphine or selective RMTg GABAergic neuron inhibition produces 87% of the maximal antinociceptive effect of systemic morphine, and RMTg GABAergic neurons modulate dopamine release in the nucleus accumbens. In addition, chemoactivation of VTA dopamine neurons significantly reduced pain behaviors both in resting and facilitated pain states and reduced by 75% the dose of systemic morphine required to produce maximal antinociception. These results provide compelling evidence that RMTg GABAergic neurons are involved in processing of nociceptive information and are important mediators of opioid analgesia.
18 citations
TL;DR: It is found that lesions of the substantia nigra pars compacta in rats induced depressive-like behaviors, and intra-LHb injection of CP-AMPAR antagonist Naspm produced antidepressant-like effects in SNc sham-lesioned and SNc-lesIONS rats, however, the doses inducing these effects were lower than that of SNc Sham-LESioned rats.
17 citations
TL;DR: Collectively, antidepressant-like effects produced by (S)-AMPA attribute to activation of LHb neurons expressing CI-AMPAR, which excites aVTA dopaminergic neurons and DRN serotonergic neurons via the direct projection, thereby increasing release of mPFC DA and 5-HT.
12 citations
TL;DR: Evidence that a major inhibitory input to DA neurons arising from the rostromedial tegmental nucleus (RMTg) plays a similarly wide range of roles that strikingly oppose multiple DA functions is reviewed, suggesting that the balance of DA and RMTg/LHb activity could regulate the Balance of behavior on a manic/depressive spectrum.
Abstract: Dopamine (DA) neurons play multiple roles in reward-related behavior,including distinct roles in learning versus performance of reward-seeking, as well as effort-based decision-making and sleep–wake regulation. We review the increasing evidence that a major inhibitory input to DA neurons arising from the rostromedial tegmental nucleus (RMTg) plays a similarly wide range of roles that strikingly oppose multiple DA functions. These roles are in part dependent on excitatory inputs from the lateral habenula (LHb), although contributions from additional forebrain and brainstem RMTg afferents are likely also important. We also review evidence that increased RMTg/LHb activity drives depressive behaviors, while reductions lead to mania-like behaviors, suggesting that the balance of DA and RMTg/LHb activity could regulate the balance of behavior on a manic/depressive spectrum.
TL;DR: Changes in the lesioned rats are associated with increased release of glutamate and up‐regulated expression of GluR1 subunit‐containing AMPA receptors in the RMTg, which suggest that degeneration of the nigrostriatal pathway enhances AMPA receptor‐mediated excitatory transmission in theRMTg.