Individual arcuate nucleus proopiomelanocortin neurons project to select target sites

Abstract

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) are a diverse group of neurons that project widely to different brain regions. It is unknown how this small population of neurons organizes its afferent projections. In this study, we hypothesized that individual ARH POMC neurons exclusively innervate select target regions. To investigate this hypothesis, we first verified that only a fraction of ARH POMC neurons innervate the lateral hypothalamus (LH), the paraventricular nucleus of the hypothalamus (PVN), the periaqueductal gray (PAG), or the ventral tegmental area (VTA) using the retrograde tracer cholera toxin B (CTB). Next, two versions of CTB conjugated to distinct fluorophores were injected bilaterally into two of the regions such that PVN and VTA, PAG and VTA, or LH and PVN received tracers simultaneously. These pairs of target sites were chosen based on function and location. Few individual ARH POMC neurons projected to two brain regions at once, suggesting that there are ARH POMC neuron subpopulations organized by their afferent projections. We also investigated whether increasing the activity of POMC neurons could increase the number of ARH POMC neurons labeled with CTB, implying an increase in new synaptic connections to downstream regions. However, chemogenetic enhancement of POMC neuron activity did not increase retrograde tracing of CTB back to ARH POMC neurons from either the LH, PVN, or VTA. Overall, subpopulations of ARH POMC neurons with distinct afferent projections may serve as a way for the POMC population to organize its many functions.

Dopamine D2-Subtype Receptors Outside the Blood-Brain Barrier Mediate Enhancement of Mesolimbic Dopamine Release and Conditioned Place Preference by Intravenous Dopamine

“…Although the exact mechanism whereby IV DA modulates VTA DA neuron activity remains unclear the evidence presented suggests that it does so at least in part through a peripheral D2R related mechanism. Previous research has shown that the VTA receives input from regions involved in the processing of interoceptive signals including the arcuate nucleus and the NTS (Geerling and Loewy, 2006 ; Alhadeff et al, 2012 ; Metz et al, 2021 ). Both these regions are part of zones where the permeability of the BBB is increased allowing for easier trafficking of molecules across the BBB.…”

Proopiomelanocortin (POMC) and psychodermatology

“…peripheral mediators crossing the blood-brain barrier. 3,12,19,23 The CNS POMC system has other functions, including coordinating the central stress response, regulation of sexual behaviour, growth, lactation, the reproductive cycle and possibly central cardiovascular control. 3,5,12,19,22 Transcriptional regulation of the POMC gene within the arcuate nucleus may generate these diverse functions.…”

“…52 This is perhaps not surprising and fits with the previous discussions about obesity, depression and HPA function. 3,12,[19][20][21][22][23][24][25][26][27]29,30,[32][33][34]43,50,51 There are wide variations in clinical outcomes in psoriasis. 53 In a cluster analysis of health literacy, a significant subgroup had lower psoriasis knowledge, quality of life, ability to self-manage and feelings of worth.…”

“…In the CNS, cell bodies for POMC are mainly located in the arcuate nucleus of the hypothalamus and the nucleus tractus solitarius of the brainstem 1–3 . Both areas have well defined functions relating to appetite and food intake 3,11,12 . Two (MC1R and MC5R) show widespread cutaneous expression 4,10 .…”

Somatization in dermatology

“…Mindfulness therapy/based stress reduction (MBT) 42 Reduces of somatic symptoms as well as the severity and number of physical symptoms can be obtained when MBT accompanied by an serotoninnorepinephrine reuptake inhibitors (SNRI) (venlafaxine).…”