Efferent projections of thyrotropin‐releasing hormone‐synthesizing neurons residing in the anterior parvocellular subdivision of the hypothalamic paraventricular nucleus

Abstract

The anterior parvocellular subdivision of the PVN (aPVN) contains non-hypophysiotropic TRH neurons that are densely innervated by feeding-related neuronal groups of the hypothalamic arcuate nucleus. To determine how these TRH neurons are integrated within the brain, the major projection fields of this cell group was studied by anterograde and retrograde tract-tracing methods. Projection sites were identified by injection of the anterograde tracer Phaseolus vulgaris leuco-agglutinin (PHAL) into the aPVN, and subsequent double immunofluorescent staining was used to visualize axons containing both PHAL and proTRH. To distinguish between the projection sites of TRH neurons residing in the aPVN and the closely situated perifornical area. the retrograde tracer, cholera toxin B subunit (CTB), was injected into regions where PHAL/proTRHcontaining axons were densely accumulated. TRH neurons in the aPVN were found to project to the hypothalamic arcuate, dorsomedial and ventral premammillary nuclei, medial preoptic region, tuber cinereum area, paraventricular thalamic nucleus, bed nucleus of the stria terminalis, lateral septal nucleus and central amygdaloid nucleus. Projection fields of perifornical TRH neurons were in partial overlap with that of the aPVN TRH cells. In addition, these neurons also innervated the hypothalamic ventromedial nucleus, the medial amygdaloid nucleus and the amygdalohippocampal area. These data suggest that through its efferent connections, aPVN TRH neurons may be involved in the regulation of energy homeostasis co-ordinately with effects on behavior, locomotor activity and thermogenesis. In addition, the major differences in the projection fields of aPVN and perifornical TRH neurons suggest that these two TRH-synthesizing neuronal groups are functionally different.

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

“…In addition, we evaluated whether proTRH mRNA levels in the anterior PVN (aPVN) changed in a manner correlated with the hyperphagia of animals, since the peptide from this subcompartment has been implicated in feeding regulation (Wittmann et al 2009a, Alvarez-Salas et al 2012. To identify the functioning of the transduction pathway of leptin in adults, we also evaluated expression patterns of target genes of leptin signaling in the arcuate nucleus (ARC) and PVN, such as Lepr and Npy, which directly or indirectly affect PVN proTRH mRNA levels during fasting.…”

Differential Adaptations of the Hypothalamus-Pituitary-Thyroid Axis Between Food Restriction and Anorexia

“…As an icv injection of TRH in different animal species, reduces their food and liquid intake (Choi et al, 2002;Karydis & Tolis, 1998;Vijayan & McCann, 1977;Vogel et al, 1979), it has been proposed as an anorexigenic factor, which has been tested in ad libitum feeding animals, in those subjected to stress-induced eating models, and also in fasted and hungry animals during the re-feeding period (Horita, 1998;Morley & Levine, 1980;Steward et al, 2003;Suzuki et al, 1982;Vijayan & McCann, 1977). As mentioned, PVN TRHergic neurons express receptors for different feeding-regulating peptides synthesized in the ARC, such as NPY, AgRP, CART and -MSH; also for leptin (Ob-Rb) which suggests that the hormone has an indirect effect on TRH expression by acting on feeding-related synthesizing neurons of the ARC, but also has a direct action on PVN TRHergic cells (Wittmann et al, 2009). As TRHergic neurons of the anterior part of the PVN are known to have projections to the ARC, to dorsomedial and to ventromedial hypothalamic nuclei, it is likely that besides its role in energy homeostasis, motivational aspects related to food intake might also be under TRH control.…”

“…Two of the major projection fields of aPVN TRH neurons are the ARC and the dorsomedial hypothalamus (DMH) (Morton et al, 2006;Wittmann et al, 2009) thus, it is possible that the observed anorectic effect of the icv administered TRH is mediated by neurons of that subdivision (Wittmann et al, 2009), but it awaits to be elucidated. Feeding-regulating role of TRH from the anterior part of the PVN TRH is also supported by studies showing an unaltered expression of the peptide in suckling rats (Sanchez et al, 2001) that are known to develop hyperphagia during lactation periods (Xu et al, 2009).…”

“…It is likely that the lack of increase in TRH synthesis only in the aPVN of suckling rats would allow them to increase their food intake. Moreover, NPY from DMH is responsible for the hyperphagic drive during lactation, a major projection field of TRHergic neurons from the aPVN (Wittmann et al, 2009).…”

“…The main projection of aPVN TRH neurons is the dorsomedial part of the ARC (Wittmann et al, 2009), a region involved in the regulation of prolactin secretion (Freeman et al, 2000), suggests that aPVN subdivision may be involved in changes induced by dehydration, however, speculations may be confirmed by in situ hybridization analysis that would allow the identification of PVN TRHergic neurons activated in DIA.…”