Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats

Abstract

New Findings r What is the central question of this study?As the parabrachial complex plays a role in the cardiorespiratory response evoked from the hypothalamic defence area (pressor response and tachycardia) and the A5 region is involved in the responses evoked from the parabrachial complex, a possible interaction between the hypothalamic defence area and A5 is suggested. Accordingly, the present study was carried out to assess this hypothesis in rats. r What is the main finding and its importance?The neuromorphological, neuropharmacological and electrophysiological results of our study demonstrate, for the first time, that the A5 region is an important component of those brainstem pathways known to be involved in mediating the autonomic changes associated with the electrically evoked defence response. In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague-Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P < 0.001 in both cases). A second group of experiments was done to examine the importance of the A5 region in modulating the cardiorespiratory response evoked from the HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P < 0.001) due to a decrease in expiratory time (P < 0.01). The respiratory response was accompanied by a pressor response (P < 0.001) and tachycardia (P < 0.001). After muscimol microinjection within the A5 region, pressor and heart rate responses to HDA stimulation were reduced (P < 0.01 and P < 0.001, respectively). The respiratory response persisted unchanged. Finally, to confirm functional interactions between the HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that

Role of the Dorso- and Ventrolateral Pons in Cardiorespiratory Hypothalamic Defense Responses

“…Moreover, there are electrophysiological evidences of interactions between HDA and A5 catecholaminergic neurons. The importance of the connections between both regions is confirmed with the observation that a significant number of these A5 neurons are activated from HDA stimulation [136]. In the same way as with PBc, antidromic and orthodromic activation are observed in A5 neurons.…”

“…A c-Fos-ir expression is induced during HDA stimulation in both A5 noncatecholaminergic (TH-negative) and A5 catecholaminergic (TH-positive) cells of the pons [136]. This increase in c-Fos expression is higher in noncatecholaminergic than in catecholaminergic neurons [136].…”

“…A c-Fos-ir expression is induced during HDA stimulation in both A5 noncatecholaminergic (TH-negative) and A5 catecholaminergic (TH-positive) cells of the pons [136]. This increase in c-Fos expression is higher in noncatecholaminergic than in catecholaminergic neurons [136]. In addition, in both populations of neurons of the A5 region, this activation seems probably to be due to a direct activation from the HDA and not due to a secondary activation to the pressure response elicited during stimulation of the HDA.…”

Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions

“…In adults, lesions of the brainstem catecholaminergic neurons reduce resting arterial pressure and breathing frequency, impair hypoxia-induced sympathoexcitatory response and depress the ventilatory response to hypercapnia (Schreihofer and Guyenet, 2000; Li and Nattie, 2006). It has been evidenced that pontine catecholaminergic neuronal groups are essential for the appropriate basal and reflex regulation of cardiorespiratory functions (Guyenet et al, 1993; Biancardi et al, 2008; Taxini et al, 2011; Lopez Gonzalez et al, 2013). Among them, the A5 area, located within the ventrolateral pons, is suggested as an important nucleus involved in cardiorespiratory control (Loewy et al, 1979b; Byrum and Guyenet, 1987; Dobbins and Feldman, 1994).…”

Monosynaptic Input Mapping of Diencephalic Projections to the Cerebrospinal Fluid-Contacting Nucleus in the Rat

“…The Pa is regarded as an integrative region that modulates the sympathetic outflow and cardiovascular activity (Coote, 2005;Li et al, 2019). Electrical stimulation of the DM and PeF results in tachycardia in rats (López-Gonzalez et al, 2013). Lesions in the VMH can aggravate the gastric mucosal injury through the vagal nerve pathway (Sun H. et al, 2018).…”