Citation

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NEURAL CIRCUITRY UNDERLYING CONTEXTUAL REGULATION OF FEAR AFTER EXTINCTION

Orsini, CA;

Fear expression after extinction is context-dependent. For example, fear to a previously conditioned stimulus (CS) is suppressed when presented within the extinction context; however, fear renews when the CS is encountered outside the extinction context. Contextual modulation of fear after extinction is mediated by a tripartite circuit consisting of the hippocampus, prefrontal cortex (PFC) and basal amygdala (BA). For instance, the prelimbic (PL) area of the PFC is selectively engaged during renewal while the inactivation of either the ventral hippocampus (VH) or BA impairs renewal. The VH has both direct projections to the BA as well as indirect projections via the PL. Thus, contextual information can be relayed from the VH to the BA through two different pathways during renewal. To examine this neural organization, we used functional retrograde tracing to assess neuronal activation, as indexed by c-fos expression, in BA-projecting neurons in the PL and VH during renewal. We found that renewal was associated with significantly more c-fos in BA-projecting neurons in the VH and PL than that induced by extinction recall. Though this indicates that both pathways are engaged during renewal, it does not reveal the necessity of each route. We therefore disconnected the VH from either the BA or PL after the extinction of conditioned fear. The elimination of either pathway severely disrupted renewal, suggesting that convergence of PL and VH input in the BA is required for renewal. Lastly, we explored whether the cellular representation of an extinguished CS is expressed in a context-dependent manner. Interestingly, the BA contained unique neuronal populations devoted to renewal or extinction recall that arose after extinction training. In contrast, the PL contained neurons that responded to the CS regardless of extinction training or context. Lastly, the VH contained a heterogeneous population of neurons that were engaged during renewal, extinction or both. As a whole, these findings indicate that convergence of VH and PL input in the BA during extinction is necessary for renewal and may yield discrete cell assemblies in the BA that respond in a context-dependent manner.