Role of the ventral pallido-accumbal projections in the susceptibility to social defeat stress

Abstract

Depression is a serious public health problem intrinsically related to chronic stress exposure. Nevertheless, not every individual exposed to stress develops stress-related disorders. This individual difference may be related to an individual's ability to adapt to aversive events, i.e. their resilience or susceptibility to stress. Recent studies using the animal model of social defeat stress (SDS), along with the use of specific region and cell manipulation are helping to elucidate the neural circuitry of depression. In this context, the nucleus accumbens and ventral pallidum are interesting candidates to be manipulated in future treatment strategies. Two distinct classes of nucleus accumbens medium spiny neurons, D1 and D2 medium spiny neurons have opposite roles in stress-induced depressive behaviors. D1 medium spiny neurons of susceptible mice have reduced frequency of miniature excitatory synaptic currents, while D2 medium spiny neurons have increased frequency of miniature excitatory synaptic currents. Furthermore, optogenetic stimulation of D1 medium spiny neurons is antidepressant, whereas D2 medium spiny neurons inhibition is prodepressant. Elevated neuronal excitability of ventral pallidum parvalbumin positive neurons is related to depressive-like behavior. Considering the extensive and reciprocal connections between these regions, pallido-accumbal projections could be interesting targets related to the susceptibility to stress. Thus, our hypothesis is that the inhibition of pallido-accumbal projections during social defeat stress could prevents the development of stress-induced depressive behavior. The aim of the present work is to evaluate the role of ventral pallidum projections to the Acb in the susceptibility to SDS and related alterations in ”FosB expression. We will use Npas1-Cre-2A-tdTomato mice exposed to chronic SDS to inhibit ventral pallidum projections to nucleus accumbens using DREADD technology and double staining of D1/D2 dopaminergic receptors and ”FosB protein in the nucleus accumbens. (AU)