The role of ventral pallidal gabaergic neurons in affective and cognitive processes

Abstract

GABAergic projections from the ventral pallidum (VP) and the associated substantia innominata (SI) are relayed to two limbic structures respectively associated with acute and chronic forms of fear: the amygdala and the bed nucleus of the stria terminalis (BNST). This implicates a key role for VP GABAergic neurons in affective processing. I carried out selective lesion experiments to identify the role of VP GABAergic neurons in several implicit and explicit processes. To reveal the functional role of these neurons, bilateral injections of GAT1-Saporin or vehicle (saline) injections were made into the VP of adult male Wistar rats (n = 16). The animals were then assessed in the forced swim test (FST), open field test (OFT), elevated plus maze (EPM), Morris water maze (MWM) and Pavlovian fear conditioning. I found that VP GAT1-Saporin lesions reduced behavioral despair while not altering general locomotor activity. The experimental animals also exhibited a reduced freezing response and increased darting behavior through the fear conditioning acquisition trials. This indicates that selectively inactivating the GABAergic neurons in the VP have an antidepressant effect while active coping mechanisms are promoted. Despair and fear memory-related differences observed in the GAT1-Saporin group may be related to the local inhibition in the basal forebrain as well as long-range GABAergic projections to the amygdala and the extended amygdala. Silencing these long-range VP GABAergic neurons may prove useful in the treatment of depressive and fear-related disorders.