Medial prefrontal depressor response: involvement of the rostral and caudal ventrolateral medulla in the rat

doi:10.1016/S0165-1838(99)00062-4

Journal of the Autonomic Nervous System

Volume 78, Issues 2–3, 14 January 2000, Pages 86-93

Journal of the Auton...

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Abstract

The importance of neurones of the caudal and rostral ventrolateral medulla (CVLM and RVLM, respectively) in mediation of the medial prefrontal cortex depressor response was studied in halothane-anaesthetised rats. Blockade of GABA_A receptors in the RVLM produced by microinjection of bicuculline (50 nl, 2 mM, n=6) resulted in reversal of the depressor (−9.5±1.2 mm Hg) and lumbar sympathetic (−6.5±5.7 units) responses to pressor (+7.8±3.5 mm Hg) and sympathoexcitatory (+19.3±12.5 units) responses and simultaneous blockade of baroreceptor reflex-mediated sympathoinhibition. Baroreflex blockade was reflected by a significant reduction in the gain (slope of the blood pressure vs. lumbar sympathetic nerve discharge regression line) of the reflex. Microinjection of the excitatory amino acid antagonist kynurenic acid (100 nl, 50 mM, n=6) into the CVLM blocked the baroreflex and significantly reduced the depressor (−9.6±0.4 to −6.9±0.6 mm Hg) and lumbar sympathetic (−4.0±2.1 to 2.9±1.9 units) responses to medial prefrontal cortex stimulation. These results support the hypothesis that the medial prefrontal cortex depressor response is mediated by a pathway which converges at the level of the RVLM and which is only partly dependent on an excitatory input to caudal ventrolateral medullary neurones.

Introduction

The infralimbic region (IL) and ventral portion of the prelimbic area (PL) of the medial prefrontal cortex (MPFC) have been implicated in the central control of autonomic function (Verberne and Owens, 1998). Depressor responses elicited by electrical stimulation of the MPFC are accompanied by sympathoinhibition (Verberne, 1996) and may also be produced by injection of chemical excitants into the MPFC suggesting that they are the result of stimulation of MPFC neurones (Verberne, 1996; Fisk and Wyss, 1997).

At present, the precise pathways mediating the MPFC-evoked depressor and sympathoinhibitory responses are poorly understood (Verberne, 1996; Verberne et al., 1997). Potentially, connections with the lateral hypothalamic area, periaqueductal grey region and structures in the medulla such as the solitary tract nucleus (NTS), may all be implicated in the underlying circuitry (Hardy and Leichnetz, 1981; van der Kooy et al., 1984; Terreberry and Neafsey, 1987; Hurley et al., 1991). We have reported previously that stimulation of the MPFC depressor region induces a pattern of c-fos gene expression in the medulla oblongata that is consistent with the notion that the depressor response is mediated by an intramedullary pathway which also mediates arterial baroreceptor reflex sympathoinhibition (Verberne et al., 1997; Owens et al., 1999). The favoured model for the intramedullary baroreflex pathway consists of: (i) glutamatergic arterial baroreceptor afferents which terminate in the NTS, relaying to (ii) glutamatergic NTS neurones projecting to GABAergic neurones within the caudal ventrolateral medulla (CVLM) which in turn project to (iii) premotor, sympathoexcitatory neurones of the rostral ventrolateral medulla (RVLM) (Guyenet et al., 1996; Chan and Sawchenko, 1998).

That the MPFC-evoked depressor response is mediated by neuronal pools which also form the basis of intramedullary circuitry involved in baroreflex sympathoinhibition is suggested by several lines of evidence. Firstly, MPFC stimulation at sites which elicit depressor and sympathoinhibitory responses inhibited the discharge of putative premotor, sympathoexcitatory neurones of the RVLM (Verberne, 1996). Secondly, inhibition of the baroreflex at the level of the NTS attenuated the MPFC-evoked depressor and sympathoinhibitory responses (Owens et al., 1999). Finally, the gain of the baroreceptor heart rate reflex is altered by excitotoxic bilateral lesions of the MPFC that include the IL and PL (Verberne et al., 1987).

In this study, we sought further physiological evidence for the involvement of the baroreflex in the MPFC-evoked depressor response using pharmacological blockade of the baroreflex pathway at the level of the RVLM and CVLM.

Section snippets

General preparation

All experimental procedures complied with the principles outlined in the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes, and were approved by the Austin Hospital Animal Welfare Committee, Melbourne, Australia. Male Sprague–Dawley rats weighing 332±59 g (280–376 g, The Animal Resources Centre, Perth, WA, Australia) were subjected to induction anaesthesia with enflurane (Ethrane; Abbott, Australasia, Sydney, Australia) followed by tracheostomy for artificial

Location of the MPFC depressor region

The MPFC depressor region was located by stimulating every 200 μm in a step wise fashion beginning 4.0 mm below the dorsal surface of the cortex. Depressor responses were generally elicited from sites 4.6 to 4.8 mm using a current intensity of 78.6±6.9 μA (50–100 μA, n=14). Electrical stimulation of the MPFC elicited a depressor response that was accompanied by a small reduction of LSND (Fig. 1A). Brief, gradual, aortic occlusion produced an elevation in arterial blood pressure and

Blockade of the baroreflex by microinjection of BIC into RVLM

In these experiments, low intensity electrical stimulation was used to elicit a depressor response from the MPFC. It remains a possibility that the MPFC depressor responses were mediated in part by stimulation of passing fibres. The location of the depressor region found in the present study is in close agreement with previous observations made our laboratory (Verberne, 1996; Owens et al., 1999) and in other laboratories (Hardy and Holmes, 1988; Fisk and Wyss, 1997). It was demonstrated that

Acknowledgements

The authors wish to thank Daniela Sartor for excellent technical assistance. This study was supported by grants from the National Health and Medical Research Council of Australia and the Austin Hospital Medical Research Foundation. A.J.M.V. is a Research Fellow of the National Health and Medical Research Council of Australia.

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¹: Present address: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3084, Australia.

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Medial prefrontal depressor response: involvement of the rostral and caudal ventrolateral medulla in the rat

Abstract

Introduction

Section snippets

General preparation

Location of the MPFC depressor region

Blockade of the baroreflex by microinjection of BIC into RVLM

Acknowledgements

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Prog. Brain Res.

Neurosci. Lett.

Neuroscience

Brain Res. Bull.

Neuroscience

Prog. Neurobiol.

Brain Res.

Brain Res.

Brain Res.

Descending projections of hypothalamic neurones with sympathetic nerve-related activity

J. Neurophysiol.

Electrophysiological study of cardiovascular neurons in the rostral ventrolateral medulla in rats

Circ. Res.

Hypothalamic and cortical sympathetic responses relay in the medulla of the rat

Am. J. Physiol.