Putative dopamine neurons in the ventral tegmental area enhance information coding in the prefrontal cortex.
Ontology highlight
ABSTRACT:
SUBMITTER: Mininni CJ
PROVIDER: S-EPMC6079091 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Conditioned inhibition is an important process to suppress learned responses for optimal adaptation, but its underlying biological mechanism is poorly understood. Here we used safety learning (SL)/fear discrimination after fear conditioning as a conditioned inhibition model because it demonstrates the essential properties of summation and retardation. Activity of the dorsomedial prefrontal cortex (dmPFC) parvalbumin (PV) neurons bidirectionally regulates spiking levels of dmPFC excitatory neurons and fear states. Responses to safety cues are increased in dopaminergic (DA) neurons in the ventral tegmental area (VTA) and in PV neurons in dmPFC after SL. Plasticity in the VTA is implicated, since SL requires activation of N-methyl-d-aspartate receptors. Furthermore, in a posttraumatic stress disorder model, impaired SL is associated with impaired potentiation of VTA DA neuron activity. Our results demonstrate a DA-dependent learning process that targets prefrontal inhibitory neurons for suppression of learned responses, and have implications for the pathogenesis and treatment of various psychiatric diseases.
| S-EPMC6600914 | biostudies-literature
Project description:The mesolimbic dopamine system contributes to a remarkable variety of behaviors at multiple timescales. Midbrain neurons have fast and slow signaling components, and specific afferent systems, such as the hippocampus (HPC) and prefrontal cortex (PFC), have been demonstrated to drive these components in anesthetized animals. Whether these interactions exist during behavior, however, is unknown. To address this question, we developed a novel analysis of human functional magnetic resonance imaging data that fits models of network excitation and inhibition on ventral tegmental area (VTA) activation. We show that specific afferent systems predict distinct temporal components of midbrain VTA signal. We found that PFC, but not HPC, positively predicted transient, event-evoked VTA activation. In contrast, HPC, but not PFC, positively predicted slow shifts in VTA baseline variability. Thus, unique functional contributions of afferent systems to VTA physiology are detectable at the network level in behaving humans. The findings support models of dopamine function in which dissociable neural circuits support different aspects of motivated behavior via active regulation of tonic and phasic signals.
| S-EPMC6075214 | biostudies-literature
Project description:Orexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.
| S-EPMC8930802 | biostudies-literature
Project description:Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6h/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training was associated with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of the Extinction group, there was an increase in postsynaptic density GluR1, PSD95, and actin proteins; while postsynaptic density mGluR5 protein decreased and there was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral tegmental area, Extinction training reversed the decreased postsynaptic density NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that extinction of drug seeking is associated with selective glutamatergic plasticity in prefrontal cortex and ventral tegmental area that include modulation of receptor trafficking to postsynaptic density.
| S-EPMC4000163 | biostudies-literature
Project description:Growing evidence indicates that midbrain dopamine (DA) cells integrate reward expectancy-related information from the prefrontal cortex to properly compute errors in reward prediction. Here we investigated how 2 major prefrontal subregions, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), contributed to DAergic prediction errors while rats performed a delay discounting task on a T-maze. Most putative DA cells in the task showed phasic responses to salient cues that predicted delayed rewards, but not to the actual rewards. After temporary inactivation of the OFC, putative DA cells exhibited strikingly reduced phasic responses to reward-predicting cues but increased responses to rewards. In contrast, mPFC inactivation significantly elevated DA responses to both predictive cues and rewards. In addition, OFC, but not mPFC, inactivation disrupted the activity of putative non-DA cells that encoded expected reward values during waiting periods. These results suggest that the 2 prefrontal subregions differentially regulate DAergic prediction errors and the OFC conveys value signals to midbrain dopamine systems.
| S-EPMC5028001 | biostudies-literature
Project description:Major depressive disorder (MDD) is a serious psychiatric disorder, with an increasing incidence in recent years. The abnormal dopaminergic pathways of the midbrain cortical and limbic system are the key pathological regions of MDD, particularly the ventral tegmental area- nucleus accumbens- medial prefrontal cortex (VTA-NAc-mPFC) neural circuit. MDD usually occurs with the dysfunction of dopaminergic neurons in VTA, which decreases the dopamine concentration and metabolic rate in NAc/mPFC brain regions. However, it has not been fully explained how abnormal dopamine concentration levels affect this neural circuit dynamically through the modulations of ion channels and synaptic activities. We used Hodgkin-Huxley and dynamical receptor binding model to establish this network, which can quantitatively explain neural activity patterns observed in MDD with different dopamine concentrations by changing the kinetics of some ion channels. The simulation replicated some important pathological patterns of MDD at the level of neurons and circuits with low dopamine concentration, such as the decreased action potential frequency in pyramidal neurons of mPFC with significantly reduced burst firing frequency. The calculation results also revealed that NaP and KS channels of mPFC pyramidal neurons played key roles in the functional regulation of this neural circuit. In addition, we analyzed the synaptic currents and local field potentials to explain the mechanism of MDD from the perspective of dysfunction of excitation-inhibition balance, especially the disinhibition effect in the network. The significance of this article is that we built the first computational model to illuminate the effect of dopamine concentrations for the NAc-mPFC-VTA circuit between MDD and normal groups, which can be used to quantitatively explain the results of existing physiological experiments, predict the results for unperformed experiments and screen possible drug targets.
| S-EPMC9373714 | biostudies-literature
Project description:Relatively little is known about the molecular control of midbrain dopamine release. Using high-fidelity imaging of pHluorin-tagged vesicular monoamine transporter 2 in dopamine neurons, we found that exocytosis was more loosely coupled to calcium entry than in fast synapses. In ventral tegmental area neurons, this allows exocytosis to be efficiently controlled by a native fast calcium buffer, calbindin-D28k, maintaining a lower vesicular release probability compared with substantia nigra neurons.
| S-EPMC3703651 | biostudies-literature
Project description:Voltammetric measurements of catecholamines in the medial prefrontal cortex (mPFC) are infrequent because of lack of chemical selectivity between dopamine and norepinephrine and their overlapping anatomical inputs. Here, we examined the contribution of norepinephrine to the catecholamine release in the mPFC evoked by electrical stimulation of the ventral tegmental area (VTA). Initially, electrical stimulation was delivered in the midbrain at incremental depths of -5 to -9.4 mm from bregma while catecholamine release was monitored in the mPFC. Although catecholamine release was observed at dorsal stimulation sites that may correspond to the dorsal noradrenergic bundle (DNB, containing noradrenergic axonal projections to the mPFC), maximal release was evoked by stimulation of the VTA (the source of dopaminergic input to the mPFC). Next, VTA-evoked catecholamine release was monitored in the mPFC before and after knife incision of the DNB, and no significant changes in the evoked catecholamine signals were found. These data indicated that DNB fibers did not contribute to the VTA-evoked catecholamine release observed in the mPFC. Finally, while the D2-receptor antagonist raclopride significantly altered VTA-evoked catecholamine release, the ??-adrenergic receptor antagonist idazoxan did not. Specifically, raclopride reduced catecholamine release in the mPFC, opposite to that observed in the striatum, indicating differential autoreceptor regulation of mesocortical and mesostriatal neurons. Together, these findings suggest that the catecholamine release in the mPFC arising from VTA stimulation was predominately dopaminergic rather than noradrenergic.
| S-EPMC4060446 | biostudies-literature
Project description:Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17?-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.
| S-EPMC5673180 | biostudies-literature
Project description:The ventral tegmental area (VTA) has been proposed to play a role in pain, but the brain structures modulating VTA activity in response to nociceptive stimuli remain unclear. Here, we demonstrate that the lateral preoptic area (LPO) glutamate neurons relay nociceptive information to the VTA. These LPO glutamatergic neurons synapsing on VTA neurons respond to nociceptive stimulation and conditioned stimuli predicting nociceptive stimulation and also mediate aversion. In contrast, LPO GABA neurons synapsing in the VTA mediate reward. By ultrastructural quantitative synaptic analysis, ex vivo electrophysiology, and functional neuroanatomy we identify a complex circuitry between LPO glutamatergic and GABAergic neurons and VTA dopaminergic, GABAergic, and glutamatergic neurons. We conclude that LPO glutamatergic neurons play a causal role in the processing of nociceptive stimuli and in relaying information about nociceptive stimuli. The pathway from LPO glutamatergic neurons to the VTA represents an unpredicted interface between peripheral nociceptive information and the limbic system.
| S-EPMC10584074 | biostudies-literature