Disinhibition of the medial prefrontal cortex reveals functionally distinct regions that influence diverse autonomic outflows in the rattus norvegicus

      The prefrontal cortex (PFC) is traditionally defined for its role in more recently evolved cognitive processes. However, evidence also suggests that this area influences autonomic function. We aimed to identify and map the cardiovascular, respiratory and thermogenic responses evoked by disinhibition of the medial PFC (mPFC) using a GABA-a receptor antagonist (bicuculline methiodide, 2 mM; BIC) as evidence suggests that strong inhibitory influences tightly regulate cortical activity. In vivo electrophysiological experiments were conducted in urethane-anaesthetised, paralysed, artificially-ventilated, male Sprague-Dawley rats which received microinjections of BIC spanning the mPFC and rostral pole of the lateral septal nucleus (LSN) (90 sites, n=10). The maps reveal functionally discrete regions centred in the ventral mPFC and the rostral LSN from which a range of autonomic outflows were altered. Within the ventral mPFC (2.52-3.00 mm rostral to Bregma), BIC at a single site in the infralimbic cortex (IL) evoked increases as large as 30% in SNA, 40 bpm in HR, 116% in PNamp, 27 bpm in PNf, 23% in expired CO2 and 0.43 °C in core temperature. Grouped by location (including unresponsive sites), sites within the IL increased SNA (12.9%±3.6), HR (17 bpm±3.8), PNamp (44.0%±18.7%), PNf (14 bpm±4), expired CO2 (5.5%±2.5) and core temperature (0.14 °C±0.07). Conversely, a number of dorsal sites in the mPFC evoked changes in respiration exclusively (increases in PNamp and irregular PNf). Disinhibition of the rostral LSN (0.72-2.28 mm rostral to Bregma) elicited directionally similar responses to the mPFC. However, distinct alterations observed in lumbar and splanchnic SNA characterised by a novel low frequency rhythmic oscillation were restricted to the LSN. These findings indicate that the mPFC and LSN exert a profound and discrete excitatory influence on thermoregulatory, respiratory and cardiovascular systems in a top-down manner. The effect on these systems is being investigated through selectively targeting catecholamines which provide significant innervation to the PFC.
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