Stimulation of mu opioid, but not GABAergic, receptors of the lateral habenula alters free feeding in rats

The lateral habenula (LHb) plays essential roles in behavioral responses to stressful events. Stress is tightly linked to autonomic responses such as cardiovascular responses, yet how the LHb regulates these responses is not well understood. To address this issue, we electrically stimulated the LHb in rats, measured its effects on heart rate (HR) and mean arterial pressure (MAP), and investigated the neural circuits that mediate these LHb-induced cardiovascular responses via the autonomic nervous system. We observed that stimulation of the LHb induced bradycardia and pressor responses, whereas stimulation of the adjacent areas changed neither the HR nor the MAP. Bilateral vagotomy and administration of a muscarinic receptor antagonist suppressed the LHb stimulation effect on the HR but not on the MAP, whereas administration of a β-adrenoceptor antagonist partly attenuated the effect on the MAP but not on the HR. Thus, the LHb-induced cardiovascular responses of the HR and the MAP were likely caused by activations of the cardiac parasympathetic nerves and the cardiovascular sympathetic nerves, respectively. Furthermore, administration of a non-selective 5-HT receptor antagonist significantly attenuated the LHb stimulation effects on both the MAP and the HR. A 5-HT2 receptor antagonist also attenuated the LHb stimulation effects. A low dose of a 5-HT1A receptor antagonist enhanced the LHb stimulation effects, but a high dose of the drug attenuated them. 5-HT1B and 5-HT1D receptor antagonists as well as a 5-HT7 receptor antagonist did not affect the LHb stimulation effects. Taken together, our findings suggest that the LHb regulates autonomic cardiovascular responses at least partly through the serotonergic system, particularly via the 5-HT1A and 5-HT2 receptors.

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Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Molecular Psychiatry ◽

10.1038/s41380-020-00906-0 ◽

2020 ◽

Author(s):

Ya-Dong Li ◽

Yan-Jia Luo ◽

Wei Xu ◽

Jing Ge ◽

Yoan Cherasse ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Gabaergic Neurons ◽

Population Activity ◽

Lateral Habenula ◽

Optogenetic Stimulation ◽

Ventral Tegmental ◽

Stimulation Of

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

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