Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

Dunigan, Anna I.; Swanson, Andrew M.; Olson, David P.; Roseberry, Aaron G.

doi:10.1002/cne.25013

Cited by 10 publications

(12 citation statements)

References 108 publications

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“…It also appears unlikely that differences in the circuit connectivity of VTA MC3R neurons would mediate these effects, as we have recently shown that male and female VTA MC3R neurons do not differ in their efferent projections or their afferent inputs (Dunigan et al, 2020). One potential explanation for the differences observed here is that there could be sex differences in the specific neurotransmitters or combinations of transmitters released from VTA MC3R neurons.…”

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 94%

“…For example, both POMC and AgRP neurons project to the VTA (Dietrich et al, 2012;Dunigan, Swanson, Olson, & Roseberry, 2020;King & Hentges, 2011), which is the center of the mesolimbic dopamine system, and MC3Rs are highly expressed in the VTA (Lippert, Ellacott, & Cone, 2014;Roselli-Rehfuss et al, 1993). MC3R -/-mice also show altered food self-administration (Mavrikaki et al, 2016) and altered sucrose preference and changes in dopamine turnover (Lippert et al, 2014), and our laboratory has shown that intra-VTA injections of melanocortin receptor agonists and antagonists altered both feeding and body weight, and sucrose intake in two-bottle choice tests and self-administration assays (A. G. Roseberry, 2013;Shanmugarajah, Dunigan, Frantz, & Roseberry, 2017;Yen & Roseberry, 2014).…”

Section: Introductionmentioning

confidence: 99%

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VTA MC3R neurons control feeding in an activity and sex-dependent manner in mice

Dunigan

Olson

Roseberry

2021

Preprint

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Increasing evidence indicates that the melanocortin and mesolimbic dopamine systems interact to regulate feeding and body weight. Because melanocortin-3 receptors (MC3R) are highly expressed in the ventral tegmental area (VTA), we tested whether VTA neurons expressing these receptors (VTA MC3R neurons) control feeding and body weight in vivo. We also tested whether there were sex differences in the ability of VTA MC3R neurons to control feeding, as MC3R -/- mice show sex-dependent alterations in reward feeding and dopamine levels, and there are clear sex differences in multiple dopamine-dependent behaviors and disorders. DREADD receptors were used to acutely activate and inhibit VTA MC3R neurons and changes in food intake and body weight were measured. Acutely altering the activity of VTA MC3R neurons decreased feeding in an activity- and sex-dependent manner, with acute activation decreasing feeding, but only in females, and acute inhibition decreasing feeding, but only in males. These differences did not appear to be due to sex differences in the number of VTA MC3R neurons, the ability of hM3Dq to activate VTA MC3R neurons, or the proportion of VTA MC3R neurons expressing tyrosine hydroxylase (TH). These studies demonstrate an important role for VTA MC3R neurons in the control of feeding and reveal important sex differences in behavior, whereby opposing changes in neuronal activity in male and female mice cause similar changes in behavior.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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VTA MC3R neurons control feeding in an activity and sex-dependent manner in mice

Dunigan

Olson

Roseberry

2021

Preprint

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“…Studies have identified the involvement of MC3Rs and MC4Rs in reward circuits. Antagonists acting on MC3Rs and MC4Rs result in alterations in reward behaviors and locomotor activity (de Vrind et al, 2021;Dunigan et al, 2021a). A reward is derived from sex behaviors and regions such as the NAc, CPu, and the VTA are involved in the reward circuit.…”

Section: Discussionmentioning

confidence: 99%

Melanocortin receptor 3 and 4 mRNA expression in the adult female Syrian hamster brain

Hall

Kohut-Jackson

Peyla

et al. 2023

Front. Mol. Neurosci.

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Melanocortin 3 receptors (MC3R) and melanocortin 4 receptors (MC4R) are vital in regulating a variety of functions across many species. For example, the dysregulation of these receptors results in obesity and dysfunction in sexual behaviors. Only a handful of studies have mapped the expression of MC3R and MC4R mRNA across the central nervous system, with the primary focus on mice and rats. Because Syrian hamsters are valuable models for functions regulated by melanocortin receptors, our current study maps the distribution of MC3R and MC4R mRNA in the Syrian hamster telencephalon, diencephalon, and midbrain using RNAscope. We found that the expression of MC3R mRNA was lowest in the telencephalon and greatest in the diencephalon, whereas the expression of MC4R mRNA was greatest in the midbrain. A comparison of these findings to previous studies found that MC3R and MC4R expression is similar in some brain regions across species and divergent in others. In addition, our study identifies novel brain regions for the expression of MC3Rs and MC4Rs, and identifies cells that co-express bothMC3 and MC4 receptors within certain brain regions.

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“…Hosp et al, 2011 identified a projection between the VTA and Mop (M1), showing the contribution of dopaminergic connections originating from the VTA in motor skill learning. Other studies showed that the VTA serves as a hub of divergence with projections to SI, LC, DR, RT (nRT) ( Dunigan et al, 2021 ), and bfd ( Aransay et al, 2015 ), all critical for the information processing in the whisker system. Finally, the novel discoveries along the neuromodulatory circuits and their integration with nuclei in the whisker system are not limited to the dopaminergic system.…”

Section: Introductionmentioning

confidence: 99%

Where top-down meets bottom-up: Cell-type specific connectivity map of the whisker system

Rault,

Bergmans,

Delfstra

et al. 2023

Preprint

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Sensorimotor computation is a closed-loop process where bottom-up information collected about the current state of the world is integrated with top-down, internally generated knowledge, task- and goal-related affordances to create an action plan. In the rodent whisker system, a canonical model of sensorimotor computation in the context of active sensing, emerging evidence suggests that neuromodulatory neurotransmitters help shape sensorimotor control of the whisker position, and contribute to context-dependent changes in whisking frequency and amplitude. Given that neuromodulatory neurotransmitters are primarily released from subcortical nuclei whose long-range projections target the rest of the central nervous system, the circuit mapping of top-down neuromodulatory control of sensorimotor nuclei in the rodent brain will help to address the mechanisms of active sensing systematically. Therefore, taking advantage of the Allen Institute's Mouse Connectivity database, we provide an updated, cell-type specific map of the sensorimotor circuits in the mouse brain. The map includes 180 projections (65 of which were not previously reported in the literature) across 18 principal and neuromodulatory neurotransmitter-releasing nuclei of the whisker system. Performing a graph network analysis of this connectome, we identify cell-type specific hubs, sources, and sinks, provide anatomical evidence for monosynaptic inhibitory projections into all stages of the ascending pathway, and show that neuromodulatory projections improve network-wide connectivity. These results argue that beyond the modulatory chemical contributions to information processing and transfer in the whisker system, the circuit connectivity features of the neuromodulatory networks position them as nodes of sensory and motor integration.

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Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons

Cited by 10 publications

References 108 publications

VTA MC3R neurons control feeding in an activity and sex-dependent manner in mice

VTA MC3R neurons control feeding in an activity and sex-dependent manner in mice

Melanocortin receptor 3 and 4 mRNA expression in the adult female Syrian hamster brain

Where top-down meets bottom-up: Cell-type specific connectivity map of the whisker system

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