Contribution of ventral pallidal cholinergic neurons to behavioral despair and fear learning

Abstract

Cholinergic neurons of the Ventral Pallidum (VP) densely innervate the Basolateral Complex (BLA) and Central Nucleus of Amygdala (CeA), and to a lesser extent project to the Bed Nucleus of the Stria Terminalis (BNST). Although basal forebrain cholinergic projections have been heavily studied in relation to cognition and explicit memory, there are very few studies that investigate the role of this neuromodulatory pathway in affective processes. The purpose of this thesis is to investigate the contribution of ventral pallidal cholinergic neurons to behavioral despair, anxiety, and fear learning. 192 IgG saporin, an immunotoxin selective to cells that contain p75 neurotrophin receptor, was bilaterally injected into the VP of eight adult male Wistar rats to eliminate cholinergic neurons. Lesioned animals were tested in the forced swim test (FST), open field test (OFT), elevated plus maze (EPM), Morris water maze (MWM) and Pavlovian fear conditioning. The results reveal that the elimination of VP cholinergic projections exhibit a reduction of behavioral despair, increased escape latency in MWM, and diminished freezing response in fear conditioning. These results indicate that elimination of VP cholinergic neurons have an antidepressant effect, while suppressing conditioned fear memory. VP cholinergic lesions also lead to deficits in hippocampus-dependent spatial learning. These results suggest that VP cholinergic neurons can be therapeutic targets in clinical depression and fear-related disorders.