Neurochemical identity and electrophysiology of defense neurocircuitries involving specific dorsal raphe subnuclei

Abstract

One of the main neurochemical systems related to anxiety and panic responses is the serotonergic system, arising from the Dorsal Raphe nucleus (DR). Previous evidence suggests that the DR is not homogeneous, but a group of distinct neuronal subpopulations, with morphological and functional differences. The serotonergic (5-HT) neurons of the dorsal region of the dorsal raphe (DRD) seem to increase anxiety-related responses, while neurons in the lateral wings of the dorsal raphe (lwDR) seem to inhibit panic-related behaviors. In a previous study of our research group the effects of Deep Brain Stimulation (DBS) applied to these two subnuclei of the DR were evaluated in the Elevated T Maze (ETM) model of anxiety. The ETM measures two distinct defensive responses, escape and inhibitory avoidance, measurements which have been associated, in terms of psychopatology, to Panic Disorder (PD) and Generalized Anxiety Disorder (GAD), respectively. Results showed that DBS applied to the DRD possesses an anxiolytic-like effect in the ETM, inhibiting avoidance responses, and increases Fos-immunoreactivity (Fos-ir) in the cingulate cortex, lateral septum and medial amigdala. On the other hand, DBS applied to the lwDR exerts panicolytic-like effects, inhibiting escape responses, and increases Fos-ir in the medial amígdala. These results corroborate the existence of two distinct neurocircuitries involved in the anxiolytic and panicolytc-like effects found. The purpose of the present study is to investigate the neurochemical and eletrophysiological identity of the neurons involved in the impairment of the anxiety and panic-like responses induced by DBS. For this, immunoistochemical double staining for the Fos protein, serotonin and GABA will be performed. These two neurotransmitter systems have been targeted by different pharmaceutical agents found in clinical settings for the treatment of both PD and GAD. Moreover, the electrophysiological activity of the two DR subnuclei will be investigated in awaken rats submitted or not to DBS in the ETM through telemetrical measurements. (AU)