Vasopressin and oxytocin excite MCH neurons, but not other lateral hypothalamic GABA neurons

Abstract

Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na(+)/Ca(2+) exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na(+)/Ca(2+) exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg(8)]vasotocin, the selective V1aR agonist [Phe(2)]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.

Melanin concentrating hormone modulates oxytocin-mediated marble burying

“…Oxytocin has been shown to depolarize MCH cells but no other GABAergic neurons in the LH, suggesting a selective innervation of this system (Yao et al, 2012). To determine whether OT neurons form direct synaptic contact with MCH neurons we used a Cre dependent, genetically modified rabies-mediated circuit mapping technique in an MCH-Cre transgenic line (Callaway, 2008; Sun et al, 2014).…”

“…MCH neurons were previously shown to be depolarized by OT neurons in the LH (Yao et al, 2012). Using rabies-mediated circuit mapping of MCH neurons we demonstrate retrograde labeling of a subpopulation of OT neurons that form direct presynaptic contact with MCH cells.…”

“…Using rabies-mediated circuit mapping of MCH neurons we demonstrate retrograde labeling of a subpopulation of OT neurons that form direct presynaptic contact with MCH cells. Both OT fibers and OXTR mRNA have been reported in the LH (Wang et al, 1996; Yoshida et al, 2009; Yao et al, 2012). In support of this observation we show that nearly 60% of MCH neurons colocalize with OT receptor, suggesting a functional relationship between these two neuropeptide systems.…”

“…The interaction between the OT and MCH systems was first shown when OT was found to depolarize MCH cells in the LH and not other LH GABAergic neurons, suggesting a selective innervation of the MCH system (Yao et al, 2012). This implies that OT is not involved in general excitation or setting a general tone in the LH, but rather selectively targets MCH neurons to facilitate MCH neurotransmission.…”

The Role of Melanin-Concentrating Hormone and Its Receptors in Energy Homeostasis

“…Like MCH, vasopressin and oxytocin can influence energy homeostasis and other behaviors. Whole-cell recording in hypothalamic brain slices from the MCH-green fluorescent protein transgenic mouse revealed that both vasopressin and oxytocin evoked a substantial excitatory effect on MCH-expressing cells (Yao et al, 2012). Both neuropeptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent manner, suggesting that vasopressin or oxytocin exerts a robust excitatory effect on presumptive GABA cells that contain MCH (Yao et al, 2012).…”