Biology subjects

Payant, M. A.

Publications and source records attributed to Payant, M. A..

4 recordsLinked to original sources

bioRxiv2024

Anorectic and anxiogenic actions of cocaine- and amphetamine-regulated transcript in the lateral septum

Cocaine-and amphetamine-regulated transcript (CART) is produced in several brain regions including the hypothalamus where it is made in cells that also produce melanin-concentrating hormone (MCH). MCH+CART cells densely innervate the lateral septum (LS), which integrates food- and mood-related behaviours. However, while MCH typically promotes feeding and anxiolysis, CART suppresses feeding and promotes anxiogenesis. The LS is a target site of the orexigenic actions of MCH, but it is not known if the actions of CART converge or oppose that of MCH in the LS. We implanted a bilateral cannula over the lateral or central LS of male and female wildtype mice and infused vehicle, CART55-102, or co-infused CART and MCH. CART did not alter chow intake but suppressed the intake of a palatable high sugar diet in male and female mice, especially when delivered in the medial LS. Furthermore, CART also prevented the orexigenic effect of MCH on palatable feeding intake when infused in the medial LS. We then assessed if CART regulated anxiety-like behaviour via the LS and found that intra-LS CART infusion reduced time spent in the center of an open field in male but not female mice. Our findings indicated that CART elicited anorectic and anxiogenic actions and may function in opposition to or independently of MCH in the LS. These outcomes suggested that putative CART and MCH co-release from MCH neurons may provide biphasic regulation of feeding and anxiety via the LS.

neuroscience↗

bioRxiv2024

Melanin-concentrating hormone promotes feeding through the lateral septum

Feeding is necessary for survival but can be hindered by anxiety or fear, thus neural systems that can regulate anxiety states are key to elucidating the expression of food-related behaviors. Melanin-concentrating hormone (MCH) is a neuropeptide produced in the lateral hypothalamus that promotes feeding and anxiogenesis. The orexigenic actions of MCH that prolong ongoing homeostatic or hedonic feeding are context-dependent and more prominent in male than female rodents, but it is not clear where MCH acts to initiate feeding. The lateral septum (LS) promotes feeding and suppresses anxiogenesis when inhibited, and it comprises the densest projections from MCH neurons. However, it is not known whether the LS is a major contributor to MCH-mediated feeding. As MCH inhibits LS cells by MCH receptor (MCHR1) activation, MCH may promote feeding via the LS. We bilaterally infused MCH into the LS and found that MCH elicited a rapid and long-lasting increase in the consumption of standard chow and a palatable, high sugar diet in male and female mice; these MCH effects were blocked by the co-administration of a MCHR1 antagonist TC-MCH 7c. Interestingly, the orexigenic effect of MCH was abolished in a novel, anxiogenic environment even when presented with a food reward, but MCH did not induce anxiety-like behaviors. These findings indicated the LS as a novel region underlying orexigenic MCH actions, which stimulated and enhanced feeding in both sexes in a context -dependent manner that was most prominent in the homecage.

neuroscience↗

bioRxiv2023

Inhibitory actions of melanin-concentrating hormone in the lateral septum

Melanin-concentrating hormone (MCH) neurons can coexpress several neuropeptides or neurotransmitters and send widespread projections throughout the brain. Notably, there is a dense cluster of nerve terminals from MCH neurons in the lateral septum (LS) that innervate LS cells by glutamate release. The LS is also a key region integrating stress- and anxiety-like behaviours that are also emerging roles of MCH neurons. However, it is not known if the MCH peptide acts within the LS or whether MCH target sites are localized. We analysed the projections from MCH neurons in male and female mice anteroposteriorly throughout the LS and found spatial overlap between the distribution pattern of MCH-immunoreactive (MCH-ir) fibers with MCH receptor Mchr1 mRNA hybridization or MCHR1-ir cells. This overlap was most prominent along the ventral and lateral border of the rostral part of the LS (LSr). Most MCHR1-labeled LS neurons laid adjacent to passing MCH-ir fibers, but some MCH-ir varicosities directly contacted the soma or cilium of MCHR1-labeled LS neurons. We thus performed whole-cell patch-clamp recordings from MCHR1-rich LSr regions to determine if and how LS cells respond to MCH. Bath application of MCH to acute brain slices activated a bicuculline-sensitive chloride current that directly hyperpolarized LS cells. This MCH-mediated hyperpolarization was blocked by calphostin C and suggested that the inhibitory actions of MCH were mediated by protein kinase C-dependent activation of GABAA receptors. Taken together, these findings defined potential hotspots within the LS that may elucidate the contributions of MCH to stress- or anxiety-related feeding behaviours. Key pointsO_LIRESEARCH QUESTION. Melanin-concentrating hormone (MCH) neurons have dense nerve terminals within the lateral septum (LS), a key region underlying stress- and anxiety-like behaviours that are emerging roles of the MCH system, but it is not known if the LS is a MCH target site. C_LIO_LINEUROANATOMY. We found spatial overlap between MCH-immunoreactive fibers, Mchr1 mRNA, and MCHR1 protein expression especially along the lateral border of the LS. C_LIO_LIELECTROPHYSIOLOGY. Within MCHR1-rich regions, MCH directly inhibited LS cells by increasing a chloride conductance in a protein kinase C-dependent manner. C_LIO_LISIGNIFICANCE. Electrophysiological MCH effects in brain slices have been elusive and even fewer have described the mechanisms of MCH action. Our findings demonstrated, to our knowledge, the first description of MCHR1 Gq-coupling in brain slices, which was previously predicted in cell or primary culture models only. Together, these findings defined hotspots and mechanistic underpinnings for MCH effects such as in stress- and anxiety-related behaviours. C_LI

neuroscience↗

bioRxiv2019

Distributions of hypothalamic neuron populations co-expressing tyrosine hydroxylase and the vesicular GABA transporter in the mouse

The hypothalamus contains catecholaminergic neurons marked by the expression of tyrosine hydroxylase (TH). As multiple chemical messengers coexist in each neuron, we determined if hypothalamic TH-immunoreactive (ir) neurons express glutamate or GABA. We used Cre/loxP recombination to express enhanced GFP fluorescence (EGFP) in neurons that express the vesicular glutamate (vGLUT2) or GABA transporter (vGAT), then determined TH immunoreactivity in glutamatergic or GABAergic neurons, respectively. EGFP-positive vGLUT2 neurons were not TH-ir. However, discrete TH-ir signals colocalized with EGFP-positive vGAT neurons, which we validated by in situ hybridization for Vgat mRNA. In order to contextualize the observed pattern of TH+EGFP colocalization in vGAT neurons, we first performed Nissl-based parcellation and plane-of-section analysis, and then mapped the distribution of TH-ir vGAT neurons onto atlas templates from the Allen Reference Atlas (ARA) of the mouse brain. TH-ir vGAT neurons were distributed throughout the rostrocaudal extent of the hypothalamus. Within the ARA ontology of gray matter regions, TH-ir neurons localized primarily to the periventricular hypothalamic zone, periventricular hypothalamic region, and lateral hypothalamic zone. There was a very strong presence of EGFP fluorescence in TH-ir neurons across all brain regions, but the most striking colocalization was found in the zona incerta (ZI) - a region assigned to the hypothalamus in the ARA - where every TH-ir neuron was EGFP-positive. Neurochemical characterization of these ZI neurons revealed that they display immunoreactivity for dopamine but not dopamine {beta}-hydroxylase. In aggregate, these findings indicate the existence of a novel hypothalamic population in the mouse that may signal through the release of GABA and/or dopamine.

neuroscience↗