Showing papers on "Rostromedial tegmental nucleus published in 2009"

Two types of dopamine neuron distinctly convey positive and negative motivational signals

Abstract: Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.

Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli

Abstract: Midbrain dopamine neurons play central roles in reward processing. It is widely assumed that all dopamine neurons encode the same information. Some evidence, however, suggests functional differences between subgroups of dopamine neurons, particularly with respect to processing nonrewarding, aversive stimuli. To directly test this possibility, we recorded from and juxtacellularly labeled individual ventral tegmental area (VTA) dopamine neurons in anesthetized rats so that we could link precise anatomical position and neurochemical identity with coding for noxious stimuli. Here, we show that dopamine neurons in the dorsal VTA are inhibited by noxious footshocks, consistent with their role in reward processing. In contrast, we find that dopamine neurons in the ventral VTA are phasically excited by footshocks. This observation can explain a number of previously confusing findings that suggested a role for dopamine in processing both rewarding and aversive events. Taken together, our results indicate that there are 2 functionally and anatomically distinct VTA dopamine systems.

The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta

Abstract: Prior studies revealed that aversive stimuli and psychostimulant drugs elicit Fos expression in neurons clustered above and behind the interpeduncular nucleus that project strongly to the ventral tegmental area (VTA) and substantia nigra (SN) compacta (C). Other reports suggest that these neurons modulate responses to aversive stimuli. We now designate the region containing them as the "mesopontine rostromedial tegmental nucleus" (RMTg) and report herein on its neuroanatomy. Dense micro-opioid receptor and somatostatin immunoreactivity characterize the RMTg, as do neurons projecting to the VTA/SNC that are enriched in GAD67 mRNA. Strong inputs to the RMTg arise in the lateral habenula (LHb) and, to a lesser extent, the SN. Other inputs come from the frontal cortex, ventral striatopallidum, extended amygdala, septum, preoptic region, lateral, paraventricular and posterior hypothalamus, zona incerta, periaqueductal gray, intermediate layers of the contralateral superior colliculus, dorsal raphe, mesencephalic, pontine and medullary reticular formation, and the following nuclei: parafascicular, supramammillary, mammillary, ventral lateral geniculate, deep mesencephalic, red, pedunculopontine and laterodorsal tegmental, cuneiform, parabrachial, and deep cerebellar. The RMTg has meager outputs to the forebrain, mainly to the ventral pallidum, preoptic-lateral hypothalamic continuum, and midline-intralaminar thalamus, but much heavier outputs to the brainstem, including, most prominently, the VTA/SNC, as noted above, and to medial tegmentum, pedunculopontine and laterodorsal tegmental nuclei, dorsal raphe, and locus ceruleus and subceruleus. The RMTg may integrate multiple forebrain and brainstem inputs in relation to a dominant LHb input. Its outputs to neuromodulatory projection systems likely converge with direct LHb projections to those structures.

Afferents to the GABAergic tail of the ventral tegmental area in the rat

Abstract: We previously showed that chronic psychostimulant exposure induces the transcription factor DeltaFosB in gamma-aminobutyric acid (GABA)ergic neurons of the caudal tier of the ventral tegmental area (VTA). This subregion was defined as the tail of the VTA (tVTA). In the present study, we showed that tVTA can also be visualized by analyzing FosB/DeltaFosB response following acute cocaine injection. This induction occurs in GABAergic neurons, as identified by glutamic acid decarboxylase (GAD) expression. To characterize tVTA further, we mapped its inputs by using the retrograde tracers Fluoro-Gold or cholera toxin B subunit. Retrogradely labeled neurons were observed in the medial prefrontal cortex, the lateral septum, the ventral pallidum, the bed nucleus of the stria terminalis, the substantia innominata, the medial and lateral preoptic areas, the lateral and dorsal hypothalamic areas, the lateral habenula, the intermediate layers of the superior colliculus, the dorsal raphe, the periaqueductal gray, and the mesencephalic and pontine reticular formation. Projections from the prefrontal cortex, the hypothalamus, and the lateral habenula to the tVTA were also shown by using the anterograde tracer biotinylated dextran amine (BDA). We showed that the central nucleus of the amygdala innervates the anterior extent of the VTA but not the tVTA. Moreover, the tVTA mainly receives non-aminergic inputs from the dorsal raphe and the locus coeruleus. Although the tVTA has a low density of dopaminergic neurons, its afferents are mostly similar to those targeting the rest of the VTA. This suggests that the tVTA can be considered as a VTA subregion despite its caudal location.

Lateral habenula projections to dopamine and GABA neurons in the rat ventral tegmental area.

Abstract: Ventral tegmental area (VTA) dopamine (DA) neurons and their forebrain projections are critically involved in reward processing and cognitive functions. Descending projections from the lateral habenula (LHb) play a central role in inhibiting DA cell activity in response to the absence of expected rewards. As LHb efferents are reportedly glutamatergic, their ability to inhibit DA cells would theoretically require a disynaptic connection involving VTA GABA neurons and their local collateral inputs to DA cells. We therefore used anterograde tract-tracing from the LHb to investigate the relative selectivity of LHb synapses onto GABA versus DA VTA neurons. LHb axons were visualized using immunoperoxidase, and DA and GABA cells were marked by immunogold-silver labeling for tyrosine hydroxylase (TH) or GABA, respectively. By ultrastructural analysis, 16% of LHb axons were observed to form synaptic contacts in the VTA, and most of these were of an intermediate morphological type that did not exhibit definitive asymmetric or symmetric character. LHb axons synaptically targeted TH- and GABA-labeled dendrites to a comparable extent (45 and 52% observed incidence, respectively). Pre-embedding immunogold labeling for the vesicular glutamate transporter type 2 and post-embedding immunogold staining for GABA confirmed that approximately 85% of LHb terminals were glutamatergic and not GABAergic. These results suggest that the robust inhibition of DA cells evoked by the LHb is unlikely to arise from a selective innervation of VTA GABA neurons. Moreover, the LHb may mediate a direct excitation of DA cells that is over-ridden by indirect inhibition originating from an extrinsic source.

The mesopontine rostromedial tegmental nucleus and the emotional motor system: Role in basic survival behavior

Abstract: In this issue of the Journal, we are publishing two papers, by Jhou and colleagues and by Kaufling and coworkers, describing a newly identified piece of brain circuitry that appears to be of great importance in inhibition of motor behaviors. The structure that is central to this circuitry is called the mesopontine rostromedial tegmental nucleus by Jhou et al., and the tail of the ventral tegmental area by Kaufling et al., but there is little doubt that they are referring to the same cell group, and that the connections of this cell group place it clearly in the framework of motivated behaviors and motor control. As recently as 35 years ago the common opinion in neurology was that voluntary motor control, especially in humans, was mainly imposed by fibers originating in the motor and premotor cerebral cortex descending through the internal capsule and cerebral peduncle to the brainstem and spinal cord. This notion was supported by clinical findings that complete interruption of this descending pathway led to contralateral hemiplegia in patients. Although a few neurologists had noticed that even hemiplegic patients would sometimes make emotional motor responses (such as smiling symmetrically when told a joke), the prevailing opinion was that emotional behaviors used the classic corticobulbar and corticospinal pathways, and that as a result most illnesses of emotional behavior did not have a basis in aberrant brain function, but had to be cured by careful personal attention. Since then neuroscience research has made it clear that those brain regions known to be involved in emotional functions have their own hardware, very similar to the projections from the motor and premotor cortex to the brainstem and spinal cord. One reason that these emotional motor systems were not recognized earlier was that they were not detected by classical degeneration-based retroand anterograde fiber tracing techniques such as the lesion-degeneration methods of Nauta and Gygax (1951) and Fink and Heimer (1967). New retrograde tracing techniques employing axonal tracers such as horseradish peroxidase (HRP), wheat germ agglutinin-HRP, FluoroGold, and cholera toxin B subunit, and anterograde tracing techniques including the autoradiographic method, Phaseolus vulgaris lectin (PHA-L), and several other techniques showed that structures belonging to or strongly connected with the limbic system also had their own descending motor output systems. These newly discovered pathways were brought together in the concept of the emotional motor system (Holstege, 1992). In order to distinguish this emotional motor system from the earlier described voluntary motor systems, the latter descending pathways were called somatic motor system. Both the emotional and somatic motor systems consist of a medial and a lateral component (Fig. 1). In the somatic motor system the medial component consists of pathways controlling directly or indirectly motoneurons innervating axial and proximal body musculature as well as motoneurons of neck and external eye muscles. They originate not only in the motor and premotor cortex, but also in several brainstem structures, such as the caudal pontine and medullary dorsomedial tegmentum, the vestibular nuclei, the deep layers of the tectum, the interstital nucleus of Cajal, and the rostral interstitial nucleus of the medial longitudinal fasciculus. The lateral component of the somatic motor system consists of descending systems that control the motoneurons innervating distal body muscles, i.e., arm, hand, leg, feet, but also orofacial muscles. Examples of descending systems belonging to the lateral component of the somatic motor system are the rubrospinal tract, albeit that this pathway is of minor importance in humans (Voogd et al., 1998), and the corticobulbospinal tracts originating in the motor and premotor cortex (for reviews, see Kuypers 1981; Holstege, 1991). Similarly, the emotional motor system consists of a medial and a lateral component. The lateral component contains the pathways that control more or less specific motor activities. Examples are the projections from the periaqueductal gray matter (PAG) to premotor interneuronal cell groups involved in the control of blood pressure, heart rate, micturition, respiration, vocalization, and mating behavior. Also the projections from the central nucleus of the amygdala, lateral bed nucleus of the stria terminalis, lateral hypothalamus, and medial orbitofrontal cortex to the caudal pontine and medullary lateral tegmentum belong to the lateral component of the emotional