Site-Specific Regulation of Stress Responses Along the Rostrocaudal Axis of the Insular Cortex in Rats

Abstract

The insular cortex (IC) has been described as a part of the central network implicated in the integration and processing of limbic information, being related to the behavioral and physiological responses to stressful events. Besides, a site-specific control of physiological functions has been reported along the rostrocaudal axis of the IC. However, a functional topography of the IC in the regulation of stress responses has never been reported. Therefore, this study aimed to investigate the impact of acute restraint stress in neuronal activation at different sites along the rostrocaudal axis of the IC. Furthermore, we evaluated the involvement of IC rostrocaudal subregions in the cardiovascular responses to acute restraint stress. We observed that an acute session of restraint stress increased the number of Fos-immunoreactive cells in the rostral posterior region of the IC, while fewer activated cells were identified in the anterior and caudal posterior regions. Bilateral injection of the non-selective synaptic inhibitor CoCl2 into the anterior region of the IC did not affect the blood pressure and heart rate increases and the sympathetically mediated cutaneous vasoconstriction to acute restraint stress. However, synaptic ablation of the rostral posterior IC decreased the restraint-evoked arterial pressure increase, whereas tachycardia was reduced in animals in which the caudal posterior IC was inhibited. Taken together, these pieces of evidence indicate a site-specific regulation of cardiovascular stress response along the rostrocaudal axis of the IC.

Pharmacological Manipulation of Corticotropin-Releasing Factor Receptors in the Anterior and Posterior Subregions of the Insular Cortex Differently Affects Anxiety-Like Behaviors in the Elevated Plus Maze in Rats

“…On the other hand, activation of CRF receptors within the posterior IC could inhibit local CeA-projecting neurons, thus causing anxiolytic effects. This idea is further supported by previous results indicating a deactivation of posterior IC neurons during stressful events [ 34 ]. However, precluding this hypothesis, a recent study identified that CRF acting via the CRF 1 receptor depolarizes pyramidal neurons within the posterior IC [ 31 ].…”

“…The injection needles (33 G, Small Parts, Miami Lakes, Florida, USA) used for intrabrain microinjection of the drugs were 1 mm longer than the guide cannulas previously fixed to the skull and were connected to a 2 μ L syringe (7002-KH, Hamilton Co., Reno, NV, USA) through a polyethylene tube (PE-10) (Clay Adams, Parsippany, NJ, USA). The drugs were injected in a volume of 100 nL/side [ 11 , 16 , 34 ].…”

“…Independent sets of animals underwent stereotaxic surgery for implantation of bilateral guide cannulas directed to either the anterior or posterior subregions of the IC and then were kept in recovery for at least four days. Definitions of the IC rostrocaudal subregions were based on previous studies [34][35][36][37][38][39]. On the test day, the animals were taken to the trial room at least 60 min before the start of the experiment for habituation to the room conditions.…”

Ischemic insular damage and stress ulcer in patients of acute ischemic stroke

“…These two major subcomponents of the insula are associated with distinct functions: The posterior insula integrates interoceptive, perceptual, and emotional processes and is functionally connected to sensory cortices, whereas the anterior insula domain mediates cognitive processing and salience and is functionally connected to the anterior cingulate cortex and temporal cortices. Damage to either region can lead to significant autonomic dysfunction and cardiac arrhythmias, with right‐hemisphere insular damage, in particular, being associated with autonomic dysfunction and cardiac arrhythmias (Tomeo et al., 2022 ). The extent of dysfunction following insular cortex lesions is evidenced by the increased rates of sudden death and consequent increased cardiac morbidity and mortality (Lin et al., 2021 ).…”

At the heart of the matter: how mental stress and negative emotions affect atrial fibrillation

“…The insular cortex also plays an important role in the central control of cardiac functions as it acts directly on the autonomic nervous system ( 103 , 104 ), and is consistently implicated in stress-related social and anxiety disorders ( 105 , 106 ). Recent work has demonstrated a site-specific regulation of cardiovascular stress response along the rostro-caudal axis of the insular cortex ( 107 ). There is also accumulating evidence indicating that acute stress impacts on the normal organisation of resting-state functional brain networks ( 108 , 109 ), which include prefrontal and insular hubs, and which may serve to enable efficient coping ( 108 ).…”