Excitatory amino acid receptors mediate asymmetry and lateralization in the descending cardiovascular pathways from the dorsomedial hypothalamus.

Carlos Henrique Xavier,Gisele Vaz,Marco Antônio Peliky Fontes,Fernanda Ribeiro Marins,Eugene Nalivaiko,Danielle Ianzer,Gustavo Batista Menezes,Augusto Martins Lima,Gustavo Rodrigues Pedrino

doi:10.1371/journal.pone.0112412

Abstract

The dorsomedial hypothalamus (DMH) and lateral/dorsolateral periaqueductal gray (PAG) are anatomically and functionally connected. Both the DMH and PAG depend on glutamatergic inputs for activation. We recently reported that removal of GABA-ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R-) sided predominance in cardiac chronotropism, and lateralization, that is, a greater increase in ipsilateral renal sympathetic activity (RSNA). In the current study, we investigated whether excitatory amino acid (EAA) receptors in the DMH–PAG pathway contribute to the functional interhemispheric difference. In urethane (1.2 to 1.4 g/kg, i.p.) anesthetized rats, we observed that: (i) nanoinjections of N-methyl D-aspartate (NMDA 100 pmol/100 nl) into the unilateral DMH produced the same right-sided predominance in the control of cardiac chronotropy, (ii) nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA responses, and (iii) blockade of EAA receptors in the unilateral DMH attenuated the cardiovascular responses evoked by injection of NMDA into either the R- or left- (L-) PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL) into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress. However, the magnitude of stress-evoked tachycardia was smallest when the EAA receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to the right-sided predominance in cardiac chronotropism. This interhemispheric difference that involves EAA receptors was observed in the DMH but not in the PAG.

Highlights

Asymmetries are the left-right differences in the properties of central nervous system and are found at different levels of the neuraxis [1,2]
The major findings of this study are as follows: i) N-methyl D-aspartate (NMDA) nanoinjected into the Right-dorsomedial hypothalamus (DMH) evoked greater cardiac chronotropic changes than did nanoinjections into the Left-DMH; ii) nanoinjection of NMDA into the unilateral DMH and periaqueductal gray (PAG) evoked lateralized increases in RSNA; and iii) blockade of excitatory amino acid (EAA) receptors in the right DMH nearly abolished stress-evoked tachycardia, whereas identical blockade in the Left-DMH, Leftand Right-PAG only attenuated the tachycardic response
The present study demonstrates that this asymmetric cardiac control by GABAA receptors involves EAA receptors in the DMH

Summary

Introduction

Asymmetries are the left-right differences in the properties of central nervous system and are found at different levels of the neuraxis [1,2]. Studies have highlighted the involvement of diencephalic and mesencephalic regions in the organization of physiological responses to stress [for review, see [7,8]]. The dorsomedial hypothalamus (DMH) region plays a key role in organizing physiological responses to emotional stress [18]. Previous studies have demonstrated that this selective GABA-ergic blockade results in DMH activation that allows for a predominant local excitatory input [20,21]. These findings suggest that both phenomena should happen simultaneously to produce the aforementioned responses

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