Functional topography of cardiovascular regulation along the rostrocaudal axis of the rat posterior insular cortex

Abstract

Cardiovascular (CV) representation has been identified within the insular cortex (IC) and a lateralization of function previously suggested. In order to further understand the role of IC on cardiovascular control, the present study compared the CV responses evoked by stimulation of N-metil-D-aspartate (NMDA) receptors in the right and left posterior IC at different rostrocaudal levels. Intracortical microinjections of NMDA were performed into the IC of male Wistar rats anaesthetized with urethane (1.4 g/kg) prepared for blood pressure, heart rate and renal sympathetic nerve activity. Gene expression of NMDA receptor subunits NR2A and NR2B in the IC was confirmed by RT-PCR. Immunofluorescence for the NMDA receptor NR1 subunit was demonstrated in the IC (coordinates anteroposterior (AP) +1.5, 0.0 and -1.5 mm). A cardiac sympathoinhibitory site was identified, more rostrally located than identified in previous studies. A site of sympathoexcitatory cardiac control was identified more caudal to this region in agreement with earlier work. Under the experimental conditions, no lateralization of cardiovascular function was identified with chemical stimulation eliciting the same responses from either left or right insular cortices. No tonic role of the insula on cardiovascular control was identified with the use of the NMDA antagonist, AP-5. Peri-insular microinjection of NMDA was without cardiovascular effect indicating the specificity of the insula as a cardiovascular regulatory site. The current study reveals a functional topography for autonomic cardiovascular control along the rostrocaudal axis of the posterior IC.

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans

“…In the same way, the anteroposterior distribution of activations or deactivations evidenced by functional neuroimaging studies varies across studies. Here, based on responses to direct electrical stimulation, we observed that the insular representation of tachycardia is more posterior than that of bradycardia and that both types of cardiac responses are equally represented in right and left insula, in agreement with electrical stimulations in animals (Marins et al, ; Oppenheimer & Cechetto, ). This is also consistent with the insular descending pathways projecting on the subcortical regions described, including the nucleus ambiguus, dorsale motor nucleus and the rostroventral medulla, through the periaqueductal gray, parabrachial nuclei, nucleus tractus solatarius, and hypothalamus (Cechetto & Chen, ; Hyam, Kringelbach, Silburn, Aziz, & Green, ; Salman, ; Saper, ; Shivkumar et al, ).…”

“…However, the location of insular subregions involved in this control shows large variations across studies, particularly along the rostro‐caudal axis. Similarly, the lateralization of cardiac regulation in the right insula for sympathetic control and in the left insula for parasympathetic control reported by some authors (Lacuey et al, ; Oppenheimer et al, ; Oppenheimer & Cechetto, ; Ruiz Vargas et al, ) was not confirmed by others (Chouchou et al, ; Marins et al, ; Szurhaj et al, ).…”

Evidence that remodeling of insular cortex neurovascular unit contributes to hypertension‐related sympathoexcitation

“…), anterior cingulate cortex (Cechetto and Chen ) and the insular cortex (Cechetto and Saper ; Oppenheimer ) are involved in the maintenance and regulation of heart rate, blood pressure and autonomic control and thus may play a role in the development of hypertension (Benarroch ; Asahina ; Marins et al. ). To this end, the insular cortex (IC), a key component of the central autonomic network, has been implicated in cardiovascular and autonomic control under physiological (Yasui et al.…”

“…; Marins et al. ) and pathological conditions, including hypertension (Butcher and Cechetto , ; Laowattana et al. ; Nagai et al.…”

Sex differences in insular cortex gyri responses to a brief static handgrip challenge

“…The insular cortex processes autonomic stimuli and regulates autonomic outflow via projections to the hypothalamus and brainstem sites [10–17]. In animals, insular regulation of autonomic functions is region specific, and this regulation appears dynamic but not necessarily tonic [18]. The human insula also activates in response to blood pressure challenges [19–21] in a region-specific manner [22].…”