• Synaptic potentiation onto lateral habenula neurons in the learned helplessness model of depression

JOAQUIN PIRIZ

Huerta Grande, Cordoba

Congreso; Segunda Reunión Conjunta en Neurociencias; 2010

Sociedad Argentina de Investigación en Neurociencias

The cellular basis of depressive disorders is poorly understood1. Recent studies inmonkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediatescommunication between forebrain and midbrain structures, can increase their activitywhen an animal fails to receive an expected positive reward or receives a stimulus thatpredicts aversive conditions (i.e. disappointment or anticipation of a negative outcome).LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2 that control reward-seeking behavior3 and participate indepressive disorders4. In this study we show in the learned helplessness, a wellestablished model of depression whereby animals show reduced escape from escapablefoot shock5, that excitatory synapses onto LHb neurons projecting to the VTA arepotentiated. Synaptic potentiation is due to an enhanced presynaptic release probability.Depleting transmitter release by repeated electrical stimulation of LHb afferents, using aprotocol that can be effective on depressed patients6, dramatically suppresses synapticdrive onto VTA-projecting LHb neurons in brain slices and significantly reduces learnedhelplessness behavior in rats. Our findings suggest an aberrant cellular process previouslyunexamined in the context of mood disorders that may be critical in the etiology ofdepression. Future studies aimed at determining the molecular signaling changesunderlying the synaptic hyperactivity in the VTA-projecting LHb neurons may lead tonovel and effective treatments potentially able to reverse some forms of depressivedisorders.