Neurotransmitter Regulation of Cellular Activation and Neuropeptide Gene Expression in the Paraventricular Nucleus of the Hypothalamus

Abstract

Norepinephrine (NE), glutamate (Glu), and GABA have been identified as important neurotransmitters governing neuroendocrine mechanisms represented in the paraventricular nucleus of the hypothalamus (PVH). Microinjection studies were used to compare the efficacy of these transmitter mechanisms in stimulating PVH output neurons. Local administration of NE provoked an increase in plasma corticosterone levels and Fos induction in the both the parvocellular and magnocellular divisions of the nucleus. This treatment also stimulated a robust increase in corticotropin-releasing factor (CRF) heteronuclear (hn) RNA in the parvocellular PVH and a more subtle, although reliable, increase in arginine vasopressin (AVP) hnRNA in this same compartment. Local administration of the GABA A receptor antagonist bicuculline methiodide (BMI) resulted in increased plasma corticosterone and, in contrast to NE treatment, Fos induction limited primarily to the parvocellular PVH.BMI elicited marked increases in both CRH and AVP hnRNAs within the parvocellular division of the nucleus. Over a wide range of concentrations, Glu failed to produce reliable increases in corticosterone secretion and induced only weak activational responses limited primarily to non-neurosecretory regions of the PVH. Local Glu administration did, however, provoke Fos induction in identified GABAergic neurons immediately adjoining the PVH, suggesting that the muted response to Glu may be a consequence of concurrent activation of local inhibitory interneurons. These results support a differential involvement of adrenergic, glutamatergic and GABAergic mechanisms in regulating neurosecretory populations of the PVH and suggest that involvement of local circuit neurons must be carefully considered in the interpretation of microinjection studies.

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

“…Stress-induced increase of CRH mRNA depends on the integrity of ascending catecholaminergic (noradrenergic) pathways originating in the brain stem (Pacak et al 1996). Stress-induced activation of parvocellular neurons and CRH synthesis can be reproduced by norepinephrine (NE) injection into the PVH that selectively increases CRH heteronuclear ( hn)RNA in the parvocellular neurosecretory neurons (Cole & Sawchenko 2002, Itoi et al 1999.…”

“…It is noteworthy that glutamatergic excitatory input does not reliably increase CRH expression in the parvocellular neurosecretory neurons (Cole & Sawchenko 2002). In contrast, pharmacological (by GABA A receptor antagonist) or genetical (GABBA A1b KO in CRH neurons) interference with inhibitory GABAergic input to the parvocellular neurons, increased CRH expression in PVN (Bali & Kovacs 2003, Cole & Sawchenko 2002, Gafford et al 2012.…”

“…In contrast, pharmacological (by GABA A receptor antagonist) or genetical (GABBA A1b KO in CRH neurons) interference with inhibitory GABAergic input to the parvocellular neurons, increased CRH expression in PVN (Bali & Kovacs 2003, Cole & Sawchenko 2002, Gafford et al 2012.…”

“…Furthermore One other important aspect of the negative feedback on HPA axis is the effect of glucocorticoids on limbic areas, which is mediated by local GABAergic inputs to the CRH neurons (Bali & Kovacs 2003, Cole & Sawchenko 2002, Cullinan et al 2008, Miklos & Kovacs 2002). …”

Ventral tegmental area involvement in pair bonding in male prairie voles

“…It is unlikely that the partner preferences induced by either NBQX or bicuculline resulted from the actions of these drugs during the behavioral testing period. The effects of these drugs are manifested within the first 3 h after administration [8,23,33,36,41]. Since the partner preference tests were conducted between 6 and 9 h after drug administration, it is likely that these drugs were no longer exerting direct effects on behavior.…”