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 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 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 Rewarding Effects of Optical Stimulation of Ventral Tegmental Area Glutamatergic Neurons

2015 ◽  
Vol 35 (48) ◽  
pp. 15948-15954 ◽  
Author(s):  
H.-L. Wang ◽  
J. Qi ◽  
S. Zhang ◽  
H. Wang ◽  
M. Morales
Keyword(s):  
Ventral Tegmental Area ◽  
Optical Stimulation ◽  
Glutamatergic Neurons ◽  
Ventral Tegmental ◽  
Stimulation Of

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.

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