Expression of ionotropic glutamate receptor subunit mRNAs in the hypothalamic paraventricular nucleus of the rat

Abstract

The hypopthalamic paraventricular nucleus (PVN) coordinates multiple aspects of homeostatic regulation, including pituitary-adrenocortical function, cardiovascular tone, metabolic balance, fluid/electrolyte status, parturition and lactation. In all cases, a substantial component of this function is controlled by glutamate neurotransmission. In this study, the authors performed a high-resolution in situ hybridization analysis of ionotropic glutamate receptor subunit expression in the PVN and its immediate surround. N-methyl-D-aspartate (NMDA) receptor 1 (NMDAR1), NMDAR2A, and NMDAR2B mRNAs were expressed highly throughout the PVN and its perinuclear region as well as in the subparaventricular zone. NMDAR2C/2D expression was limited to subsets of neurons in magnocellular and hypophysiotrophic regions. In contrast with NMDA subunit localization, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate)-preferring and kainate (KA)-preferring receptor subunit mRNAs were expressed heterogeneously in the PVN and surround. Glutamate receptor 1 (GluR1) mRNA labeling was most intense in preautonomic subregions, whereas GluR2, GluR4, GluR5, and KA2 were expressed in hypophysiotrophic cell groups. It is noteworthy that GluR5 mRNA expression was particularly robust in the dorsolateral region of the medial parvocellular PVN, suggesting localization in corticotropin-releasing hormone neurons. All four AMPA subunits and GluR6 and GluR7 mRNAs were expressed highly in the perinuclear PVN region and the subparaventricular zone. These data suggest the capacity for multifaceted regulation of PVN function by glutamate, with magnocellular neurons preferentially expressing NMDA subunits, preautonomic neurons preferentially expressing AMPA subunits, and hypophysiotrophic neurons preferentially expressing KA subunits. Localization of all species in the perinuclear PVN suggests that glutamate input to the immediate region of the PVN may modulate its function, perhaps by communication with local gamma-aminobutyric acid neurons.

Modulation of cardiorespiratory function mediated by the paraventricular nucleus

“…These regions controlling autonomic function express GABA A receptors (Cullinan and Wolfe, 2000; Genest et al, 2007) as well as NMDA and non-NMDA receptors (Herman et al, 2000). Neurons that project from the PVN are quiescent under basal conditions, indicating that GABAergic tone dominates the inhibitory-excitatory balance in the PVN (Bains and Ferguson, 1995; Lovick and Coote, 1988).…”

Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle

“…The NMDAR is believed to be a tetrameric receptor (Laube et al , 1998; Mano and Teichberg, 1998; Rosenmund et al , 1998), and is composed of multiple subunits (NR1, NR2a–d, NR3a–b; Table 1). In the hypothalamus, NR1, NR2a and NR2b are abundant and are co-expressed on GnRH cell bodies (Eyigor et al , 2001; Gore et al , 2000b; Herman et al , 2000; Meeker et al , 1994; Miller and Gore, 2002). Non-NMDARs form tetrameric channels which, for AMPA-type receptors, may contain any of four subunits (GluR1-4), all of which are present in the hypothalamus and are co-expressed with GnRH neurons, although GluR1-2 appear to be the most abundantly expressed (Bailey et al , 2006; Eyigor et al , 2001).…”

GluR5-mediated glutamate signaling regulates hypothalamo–pituitary–adrenocortical stress responses at the paraventricular nucleus and median eminence

“…Anatomical evidence suggests that receptors from the n-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptor families, as well as metabotropic receptors, are localized in CRH-containing regions of the PVN (Herman et al, 2000; Scaccianoce et al, 2003; Eyigor et al, 2005; Ziegler et al, 2005). Antagonist studies have demonstrated functional roles for ionotropic (Ziegler and Herman, 2000) and metabotropic (Johnson et al, 2001; Scaccianoce et al, 2003) glutamate receptors in regulation of the HPA axis.…”

“…One possibility is suggested by the preferential expression of mRNA from the kainate family of receptors in hypophysiotrophic neurons in the PVN (Herman et al, 2000). In addition, kainate has an excitatory influence on the HPA axis when administered directly into the PVN (Zelena et al, 2005), suggesting a role for kainate receptors in HPA axis regulation.…”

“…A possible role of kainate receptors in HPA axis regulation is further supported by increased expression of GluR5 and KA2 kainate receptors in response to hypoglycemia stress (Koenig and Cho, 2005). Because GluR5 mRNA and protein have both been reported to be expressed in the PVN (Herman et al, 2000; Eyigor et al, 2005), the current study investigates the role of GluR5 signaling in regulation of the HPA axis. These experiments were designed to test the hypothesis that GluR5 mediates stress-induced excitation of the PVN and activation of the HPA axis.…”