Brainstem origins of glutamatergic innervation of the rat hypothalamic paraventricular nucleus

Abstract

Multiple lines of evidence document a role for glutamatergic input to the hypothalamic paraventricular nucleus (PVH) in stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. However, the neuro-anatomical origins of the glutamatergic input have yet to be definitively determined. We have previously shown that vesicular glutamate transporter 2 (VGLUT2) is the predominant VGLUT isoform expressed in the basal forebrain and brainstem, including PVH-projecting regions, and that the PVH is preferentially innervated by VGLUT2-immunoreactive terminals/boutons. The present study employed a dual-labeling approach, combining immunolabeling for a retrograde tract tracer, Fluoro-Gold (FG), with in situ hybridization for VGLUT2 mRNA, to map the brainstem and caudal forebrain distribution of glutamatergic PVH-projecting neurons. The present report presents evidence for substantial dual labeling in the periaqueductal gray, caudal portions of the zona incerta and subparafascicular nucleus, and the lateral parabrachial nucleus. The current data also suggest that relatively few PVH-projecting neurons in ascending raphe nuclei, nucleus of the solitary tract, or ventrolateral medulla are VGLUT2 positive. The data reveal multiple brainstem origins of glutamatergic input to PVH that are positioned to play a role in transducing a diverse range of stressful stimuli.

In a rat model of panic, corticotropin responses to dorsal periaqueductal gray stimulation depend on physical exertion

“…Indeed, Pittman et al (1979) had long shown that PAG stimulations excited only 2 of 188 neurons tested in the PVN. These observations were corroborated by a recent study of Ziegler et al (2012) showing that the PAG excitatory projections to PVN arise only from the commissural and ventrolateral PAG. The latter regions are either much rostral or much ventral to the stimulated sites of the present study, respectively.…”

“…The HPA axis unresponsiveness to DPAG stimulations is also supported by the lack of DPAG projections to the PVN (Pittman et al, 1979;Floyd et al, 1996;Ziegler et al, 2012). Indeed, Pittman et al (1979) had long shown that PAG stimulations excited only 2 of 188 neurons tested in the PVN.…”

“…Rostrocaudally, 95% of electrodes were localized at intermediate (−6.1 to −6.8 mm) and caudal (−7.04 to −8.2 mm) levels of PAG. Most importantly, there were no electrodes either in commissural or in ventrolateral areas of PAG known to send glutamatergic projections to the PVN (Floyd et al, 1996;Ziegler et al, 2012).…”

Central Autonomic System

“…The PAG also has reciprocal connections with the hypothalamus (including a recently described glutamatergic projection Carstens et al, 1990;Reichling and Basbaum, 1991;Rizvi et al, 1992;Ziegler et al, 2012), NTS (Ross et al, 1981;Bandler and Tork, 1987;Farkas et al, 1997), RVL (Van Bockstaele et al, 1991;Van Bockstaele and Aston-Jones, 1992), and spinal cord (Skirboll et al, 1983). The ventrolateral PAG, especially near the border of the aqueduct, contains a population of dopaminergic neurons that have been identified as the dorsocaudal part of the A10 group (Hasue and Shammah-Lagnado, 2002).…”

Involvement of non-NMDA glutamate receptors of the hypothalamic paraventricular nucleus in the cardiovascular response to the microinjection of noradrenaline into the dorsal periaqueductal gray area of rats

“…n Statistically different (po0.05) from NA effect when injected on first day. However, it has been proposed that there is no direct glutamatergic projection from the dorsal portion of the PAG to the PVN; it is suggested that there is an indirect neuroanatomic pathway that connects these areas through glutamatatergic afferent projections from the rostral part of the PAG to the PVN, and thereby the dPAG might modulate neuroendocrine and pre-autonomic components of the PVN (Ziegler et al, 2012). L-glutamate (L-glu) is an abundant excitatory amino acid in the central nervous system (CNS), and PVN and SON neurons are known to receive dense glutamate innervations, and to express glutamate receptors (Boudaba and Tasker, 2006;Herman et al, 2000;Meeker et al, 1994).…”