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Involvement of the dorsal hippocampus in the modulation of cardiac baroreflex activity: implication of NMDA, CB1, TRPV1 and muscarinic receptors and of the nitric oxide.

Grant number: 11/19494-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2012
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Pharmacology - Autonomic Pharmacology
Principal researcher:Leonardo Resstel Barbosa Moraes
Grantee:Nilson Carlos Ferreira Junior
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The hippocampus is part of limbic system, which can be subdivided in dorsal hippocampus (DH) and ventral hippocampus (VH). The limbic system is involved in the integration of autonomic and emotional responses. It may modulate cardiovascular responses associated with stressful situations. During aversive situation there is blood pressure (BP) increases together with rise of heart rate (HR). This is due, at least in part, to a reduction of baroreflex sensitivity. This reduction is characterized by a reset in the reflex response of HR to higher BP values. The baroreflex is a reflex neural mechanism responsible for maintaining the BP in homeostatic levels. This BP control occurs beat-to-beat through modulation of variables such as HR, systolic volume and peripheral vascular resistance. The neurocircuitry involved with baroreflex modulation include areas of the brain stem such as the nucleus of the solitary tract (NTS), the dorsal and ambiguous vague nucleus, rostral and caudal ventrolateral medulla. However, studies show that forebrain areas such as the bed nucleus of the stria terminalis, the medial prefrontal cortex and DH are also involved with baroreflex activity modulation. The DH neurotransmission inhibition increases the tachycardic and bradycardic reflex responses evoked by intravenous infusion of vasoactive drugs, showing a DH inhibitory influence on baroreflex response. The glutamate (Glu) is a DH neurotransmitter involved with modulation of both autonomic and cardiovascular activity. Glutamatergic terminals and ionotropic receptors were identified within the mice DH. Moreover, administration of Glu into DH was able to evoke cardiovascular responses, suggesting that the glutamatergic system within the DH could modulate the cardiovascular activity. Moreover, the increase in BP and HR evoked by administration of Glu into DH is dependent of the activation of the neuronal isoform of the enzyme that synthesizes nitric oxide (NO), suggesting the existence of an interaction between NMDA receptors and NO within the DH, modulating the cardiovascular system. Finally, it has been shown that Glu release within the DH can be reduced by endocannabinoids through pre-synaptic CB1 receptors activation. However, the role of the DH Glu in the baroreflex modulation has not been studied, as well as the pathway NMDA/NO, and also a possible interaction of the endocannabinoid system with this pathway on baroreflex response. Thus, the proposal this study is to verify the involvement of the glutamatergic neurotransmission, nitrergic and endocannabinoid within the DH on the baroreflex activity modulation.

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LAGATTA, DAVI C.; KUNTZE, LUCIANA B.; FERREIRA-JUNIOR, NILSON C.; RESSTEL, LEONARDO B. M.. Medial prefrontal cortex TRPV1 and CB1 receptors modulate cardiac baroreflex activity by regulating the NMDA receptor/nitric oxide pathway. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 10, p. 1521-1542, . (11/19494-8)
FERREIRA-JUNIOR, NILSON CARLOS; LAGATTA, DAVI CAMPOS; MORAES RESSTEL, LEONARDO BARBOSA. Glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the dorsal hippocampus modulate the cardiac baroreflex function in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 2, p. 395-411, . (11/19494-8, 11/07332-3)
LAGATTA, DAVI C.; FERREIRA-JUNIOR, NILSON C.; DEOLINDO, MILENA; CORREA, FERNANDO M. A.; RESSTEL, LEONARDO B. M.. Ventrolateral periaqueductal grey matter neurotransmission modulates cardiac baroreflex activity. European Journal of Neuroscience, v. 44, n. 11, p. 2877-2884, . (11/19494-8)
KUNTZE, LUCIANA BAERG; FERREIRA-JUNIOR, NILSON CARLOS; LAGATTA, DAVI CAMPOS; MORAES RESSTEL, LEONARDO BARBOSA. Ventral hippocampus modulates bradycardic response to peripheral chemoreflex activation in awake rats. Experimental Physiology, v. 101, n. 4, p. 482-493, . (11/19494-8)
FERREIRA-JUNIOR, NILSON C.; FEDOCE, ALESSANDRA G.; ALVES, FERNANDO H. F.; RESSTEL, LEONARDO B. M.. Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses. Journal of Neuroscience Research, v. 91, n. 10, p. 1338-1348, . (11/07332-3, 11/19494-8, 11/20762-7, 10/09462-9)
TRINDADE FORTALEZA, EDUARDO ALBINO; FERREIRA-JUNIOR, NILSON CARLOS; LAGATTA, DAVI CAMPOS; MORAES RESSTEL, LEONARDO BARBOSA; AGUIAR CORREA, FERNANDO MORGAN. The medial amygdaloid nucleus modulates the baroreflex activity in conscious rats. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 193, p. 44-50, . (11/19494-8, 12/18556-2)
FERREIRA-JUNIOR, NILSON CARLOS; LAGATTA, DAVI CAMPOS; FABRI, DENISE RESENDE; FERRARI ALVES, FERNANDO HENRIQUE; AGUIAR CORREA, FERNANDO MORGAN; MORAES RESSTEL, LEONARDO BARBOSA. Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site-dependent manner in rats. Experimental Physiology, v. 102, n. 1, p. 14-24, . (11/07332-3, 11/19494-8)

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