scholarly journals Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andrew J. Kesner ◽  
Rick Shin ◽  
Coleman B. Calva ◽  
Reuben F. Don ◽  
Sue Junn ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Theta Oscillations ◽  
Mesolimbic Dopamine ◽  
Sucrose Consumption ◽  
Behavioral Interaction ◽  
Hypothalamic Structure ◽  
Hippocampal Theta ◽  
Substances Of Abuse ◽  
Stimulation Of

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

scholarly journals Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction

2020 ◽  
Author(s):  
Andrew J. Kesner ◽  
Rick Shin ◽  
Coleman B. Calva ◽  
Reuben F. Don ◽  
Sue Junn ◽  
...  
Keyword(s):  
Substance Use ◽  
Dopamine Neurons ◽  
Theta Oscillations ◽  
Approach Motivation ◽  
Mesolimbic Dopamine ◽  
Sucrose Consumption ◽  
Hypothalamic Structure ◽  
Hippocampal Theta ◽  
Substances Of Abuse ◽  
Stimulation Of

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to illuminate how SuM neurons mediate such effects. The excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by the projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway is important in reinforcement and approach motivation and may play an important role in mood and substance-use disorders.

scholarly journals Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-related behaviours

2020 ◽  
Author(s):  
Catherine S. Thomas ◽  
Madiha Rana ◽  
Min Qiao ◽  
Stephanie L. Borgland
Keyword(s):  
Ventral Tegmental Area ◽  
Real Time ◽  
Place Preference ◽  
Dopamine Neurons ◽  
Potential Contribution ◽  
Mesolimbic Dopamine ◽  
Optical Stimulation ◽  
Lateral Hypothalamic ◽  
Ventral Tegmental ◽  
Stimulation Of

ABSTRACTReward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin (LHox/dyn). Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (OXR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LHox/dyn-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LHox/dyn inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and place preference, and increases the incentive value attributed to a Pavlovian food cue. LHox/dyn potentiation of NAc dopamine release and real time place preference was completely blocked by an OXR1 antagonist. Thus, rewarding effects associated with optical stimulation of LHox/dyn inputs in the VTA are predominantly driven by orexin rather than dynorphin.

scholarly journals Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours

2021 ◽  
Author(s):  
Catherine S. Thomas ◽  
Aida Mohammadkhani ◽  
Madiha Rana ◽  
Min Qiao ◽  
Corey Baimel ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Real Time ◽  
Place Preference ◽  
Dopamine Neurons ◽  
Mesolimbic Dopamine ◽  
Optical Stimulation ◽  
Lateral Hypothalamic ◽  
Reward Seeking ◽  
Ventral Tegmental ◽  
Stimulation Of

AbstractReward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin.

scholarly journals Estradiol enhances ethanol stimulation of ventral tegmental area dopamine neuron firing without limiting ethanol inhibition onto those neurons

2020 ◽  
Author(s):  
Philip Stanhope Lambeth ◽  
Amy W. Lasek ◽  
Regina A. Mangieri
Keyword(s):  
Firing Rate ◽  
Ventral Tegmental Area ◽  
Brain Slices ◽  
Brain Regions ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Synaptic Inhibition ◽  
Ventral Tegmental ◽  
Additional Support ◽  
Stimulation Of

Females can progress to alcohol and other substance use disorders more quickly than males. The ovarian hormone 17β-estradiol (E2) contributes to sex differences observed in drug use and abuse and may be a principal driver of these differences. However, it is not entirely clear how E2 acts to affect processing of ethanol reward, and several brain regions and mechanisms are implicated. We sought to clarify the role of E2 in modulating the response of ventral tegmental area dopamine neurons to ethanol. To this end, we recorded spontaneous action potentials and inhibitory post synaptic currents from dopaminergic neurons in acute horizontal brain slices from ovariectomized (OVX) dopamine neuron reporter mice (Pitx3-eGFP) treated with either vehicle (VEH) or E2. On the basis of prior work, we hypothesized that E2 administration would cause dopamine cells from OVX+E2 animals to show a more substantial ethanol-induced increase in firing rate compared to control animals. Our data confirmed that ethanol stimulation of the firing rate of dopamine neurons from OVX+E2 mice was greater than that of OVX+VEH animals. Further, we hypothesized that the firing rate increase would be accompanied by a concomitant decrease in ethanol stimulated inhibition onto those same neurons. We found that although ethanol caused the expected increase in GABAA receptor-mediated synaptic inhibition in both groups, there was no difference in this response between OVX+E2 and OVX+VEH animals. Our findings lend additional support for the ability of E2 to enhance ventral tegmental area dopamine neuron responses to ethanol and suggest that this effect is not mediated by an E2-elicited suppression of synaptic inhibition.

scholarly journals Inhibition of Morphine- and Ethanol-Mediated Stimulation of Mesolimbic Dopamine Neurons by Withania somnifera

2019 ◽  
Vol 13 ◽  
Author(s):  
Valentina Bassareo ◽  
Giuseppe Talani ◽  
Roberto Frau ◽  
Simona Porru ◽  
Michela Rosas ◽  
...  
Keyword(s):  
Withania Somnifera ◽  
Dopamine Neurons ◽  
Mesolimbic Dopamine ◽  
Stimulation Of

Response of ventral pallidal neurons to amygdala stimulation and its modulation by dopamine projections to nucleus accumbens

1983 ◽  
Vol 50 (1) ◽  
pp. 148-161 ◽  
Author(s):  
C. Y. Yim ◽  
G. J. Mogenson
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Inhibitory Response ◽  
Ventral Pallidum ◽  
Procaine Hydrochloride ◽  
Acute Administration ◽  
Limbic Structure ◽  
Mesolimbic Dopamine ◽  
Ventral Tegmental ◽  
Stimulation Of

It has been shown that the nucleus accumbens receives input from the amygdala and that mesolimbic dopaminergic projection from the ventral tegmental area (VTA) modulates the response of accumbens neurons to amygdala input. Since the nucleus accumbens projects to the ventral pallidum, the purpose of this study was to investigate, using electrophysiological techniques, whether or not the nucleus accumbens relays the projection from the amygdala to the ventral pallidum and whether or not the mesolimbic dopamine projection interacts with this pathway. Extracellular single-unit recordings were obtained from the ventral pallidum of urethan-anesthetized rats, and the responses of these neurons to electrical stimulation of the amygdala were investigated. Of 392 neurons tested, 36% were inhibited and 11% were excited following amygdala stimulation. Latency of onset of inhibitory responses showed a bimodal distribution with peaks in the ranges of 4-6 ms and 16-18 ms, respectively. Fifty-four percent of inhibitory responses with latencies greater than 12 ms were attenuated by 1) injection of procaine hydrochloride into the nucleus accumbens, or 2) injection of d-amphetamine into the nucleus accumbens, or 3) stimulation of VTA with a train of 10 pulses (10 Hz) prior to stimulation of amygdala. Acute administration of haloperidol intraperitoneally or injection of 6-hydroxydopamine into the ipsilateral VTA, 2 days prior to the recording experiment, reduced the attenuating effects of intra-accumbens injection of d-amphetamine and VTA conditioning stimulations on the inhibitory response of ventral pallidal neurons to amygdala stimulation. These results support the hypothesis that the nucleus accumbens provides a link between the amygdala and the ventral pallidum. Since the amygdala is a limbic structure and the ventral pallidum has possible connections with the extrapyramidal motor system, it is suggested that the amygdala to nucleus accumbens to ventral pallidum projection may be a bridge between the limbic and motor systems. We also suggest that this relay of output from the amygdala to the ventral pallidum via the nucleus accumbens is under the modulating influence of the mesolimbic dopamine projection from the ventral tegmental area.

scholarly journals Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

2018 ◽  
Author(s):  
M.D. Valyear ◽  
I. Glovaci ◽  
A. Zaari ◽  
S. Lahlou ◽  
I. Trujillo-Pisanty ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Neural Mechanisms ◽  
Dopamine Neurons ◽  
Environmental Cues ◽  
Contextual Cues ◽  
Mesolimbic Dopamine ◽  
Neutral Context ◽  
Dopamine Circuits ◽  
Alcohol Seeking

ABSTRACTDiscrete and contextual cues that predict alcohol trigger alcohol-seeking. However, the extent to which context influences alcohol-seeking triggered by discrete cues, and the neural mechanisms underlying these responses, are not well known. We show that, relative to a neutral context, a context associated with alcohol persistently elevated alcohol-seeking triggered by a discrete cue, and supported higher levels of priming-induced reinstatement. Alcohol-seeking triggered by a discrete cue in a neutral context was reduced by designer receptor-mediated inhibition of ventral tegmental area (VTA) dopamine neurons in TH::Cre rats. Inhibiting terminals of VTA dopamine neurons in the nucleus accumbens (NAc) core reduced alcohol-seeking triggered by a discrete cue, irrespective of context, whereas inhibiting VTA dopamine terminals in the NAc shell selectively reduced the elevation of alcohol-seeking triggered by a discrete cue in an alcohol context. This dissociation highlights unique roles for divergent mesolimbic dopamine circuits in alcohol-seeking driven by discrete and contextual environmental cues.

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