Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

Abstract

When energy balance is altered by aerobic exercise, starvation, and cold exposure, for example, there appears to be coordination of the responses of skeletal muscle, white adipose (WAT), and brown adipose (BAT) tissues. We hypothesized that WAT, BAT, and skeletal muscle may share an integrated regulation by the central nervous system (CNS); specifically, that neurons in brain regions associated with energy balance would possess neuroanatomical connections to permit coordination of multiple, complementary responses in these downstream tissues. To study this, we used trans‐neuronal viral retrograde tract tracing, using isogenic strains of pseudorabies virus (PRV) with distinct fluorescent reporters (either eGFP or mRFP), injected pairwise into male rat gastrocnemius, subcutaneous WAT and interscapular BAT, coupled with neurochemical characterization of specific cell populations for cocaine‐ and amphetamine‐related transcript (CART), oxytocin (OX), corticotrophin releasing hormone (CRH) and calcitonin gene‐related peptide (CGRP). Cells in the paraventricular (PVN) and parabrachial (PBN) nuclei and brainstem showed dual projections to muscle + WAT, muscle + BAT, and WAT + BAT. Dual PRV‐labeled cells were found in parvocellular, magnocellular and descending/pre‐autonomic regions of the PVN, and multiple structural divisions of the PBN and brainstem. In most PBN subdivisions, more than 50% of CGRP cells dually projected to muscle + WAT and muscle + BAT. Similarly, 31–68% of CGRP cells projected both to WAT + BAT. However, dual PRV‐labeled cells in PVN only occasionally expressed OX or CRH but not CART. These studies reveal for the first time both separate and shared outflow circuitries among skeletal muscle and subcutaneous WAT and BAT.

Effects of Combined Oxytocin and Beta-3 Receptor Agonist (CL 316243) Treatment on Body Weight and Adiposity in Male Diet-Induced Obese Rats

“…Recent anatomical data indicate the existence of both shared and separate CNS circuits that control SNS outflow to IBAT and IWAT ( Nguyen et al, 2016 ). In particular, parvocellular PVN OT neuronal cell bodies have been found to project to IBAT ( Oldfield et al, 2002 ; Doslikova et al, 2019 ), EWAT ( Shi and Bartness, 2001 ; Stanley et al, 2010 ) and IWAT ( Shi and Bartness, 2001 ; Doslikova et al, 2019 ) and a small subset of PVN OT neurons overlap and project to both IBAT and IWAT ( Doslikova et al, 2019 ). OT neurons are thus anatomically positioned to control SNS outflow to IBAT and IWAT to regulate fat mass and adipocyte size.…”

Sex and age influence gonadal steroid hormone receptor distributions relative to estrogen receptor β‐containing neurons in the mouse hypothalamic paraventricular nucleus

“…For example, previous reports have shown that ERβ‐containing neurons in the PVN colocalize OT (Oyola et al, 2017), and the expression of OT in these neurons is completely abolished in ERβ knock‐out male mice (Nomura et al, 2002). Functionally, OT is involved in energy balance (Doslikova et al, 2019; Maejima et al, 2018), food intake regulation (Maejima et al, 2018), and sodium (Almeida‐Pereira et al, 2016) balance, processes that, when dysregulated, can contribute to autonomic dysfunction, including hypertension. Thus, the greater number of ERβ‐containing PVN cells in neuroendocrine regions known to express OT neurons suggests a mechanism whereby ERβ may preferentially contribute to autonomic dysfunction in females.…”

Mapping the vocal circuitry of Alston’s singing mouse with pseudorabies virus

“…This seems likely to be a novel elaboration of vocal circuitry in the singing mouse. A second is the high level of bilateral infection we see in this circuit compared to some other reports (Doslikova et al 2019, Hettigoda et al 2015. The third and final difference is that most models of mammalian vocalization posit that descending forebrain projections from the hypothalamus influence vocalization through effects on the PAG (Jurgens REF, Tschida REF); in our data, however, robust double-labeling within PAG appeared either coincident with or following double-labeling in the hypothalamus -a pattern that suggests the hypothalamus may have some modulatory role that is not mediated by the PAG.…”

“…Before discussing such interpretations, it is worthwhile to provide some caveats. The first is that in dual-labeling studies with virally infected neurons, the presence of one virus infection might limit infection by a second, a phenomenon known as the "principle of exclusion" or "superinfection inhibition" (Kobiler et al 2010, Doslikova et al 2019, Saleeba et al 2019. The widespread and regionspecific presence of double-labelling in our study, however, suggests this may not be a major concern (Figure 13).…”

“…Lastly, the availability of multiple isogenic strains of PRV-Bartha allows dual labeling of neurons that shape activity of different end-organs (Hogue, Card, Rinaman, Staniszewska Goraczniak, & Enquist, 2018). Although the dual isogenic PRV approach has been used extensively to examine the control of feeding, homeostasis and sympathetic function (Doslikova et al, 2019;Pérez et al, 2011;Stanley et al, 2010;Wee, Lorenz, Bekirov, Jacquin, & Scheller, 2019;Wiedmann, Stefanidis, & Oldfield, 2017), to our knowledge it has not been used in the context of vocalization.…”