Likhtik E, Popa D, Apergis-Schoute J, Fidacaro GA, Pare D (2007) Lesion of intercalated (ITC) amygdala neurons interfere with extinction of classically conditioned fear responses. Neuroscience 2007 Abstracts 426.6/HHH29. Society for Neuroscience, San Diego, CA.
Summary: The acquisition of conditioned fear responses (CRs) is thought to involve the potentiation of synapses conveying information about the conditioned stimulus (CS) to the basolateral (BLA) amygdala. Expression of CRs would depend on the transfer of potentiated CS inputs by the BLA to the central amygdala (CE). In contrast, the mechanisms of extinction remain controversial. It has been proposed that ITC neurons, which receive BLA inputs and generate feedforward inhibition in CE, are in a key position to mediate extinction. In this view, NMDA-dependent potentiation of BLA inputs to ITC cells during extinction training, would dampen the impact of CS-related BLA activity on CE neurons, inhibiting CRs. However, this idea is difficult to test because ITC cells occur in small, lateromedially dispersed clusters, making conventional lesioning methods inadequate. Here, we took advantage of the fact that, compared to the rest of the amygdala, ITC cells express a much higher concentration of mu opioid receptors (muORs). As a result, we could lesion them by performing local injections of a peptide-toxin conjugate (demorphin conjugated to saporin, D-Sap) that selectively targets cells expressing muORs. Control rats received injections of saporin conjugated to a blank peptide (B-Sap). On Day 1, intact rats were subjected to a standard cued fear conditioning protocol in context A. On Day 2, they received 20 CS alone presentations in a different context (B). On Day 3, rats then received either D-Sap or B-Sap injections in the ITC cell masses. One week later, extinction recall was tested in context B with 10 CS alone presentations. Compared to control (B-Sap) rats (n=10), ITC-lesioned rats (n=5) had an extinction deficit (ANOVA, F=11.687, p = 0.005). Post-hoc t-tests comparing % time freezing during the first five or last five CSs revealed that rats with ITC lesions had significantly higher freezing levels throughout the extinction recall test (p<0.002 for both tests). These differences were not attributable to a non-specific increase in freezing or anxiety levels as exploratory behaviors in a novel open field in control and ITC-lesioned rats were indistinguishable. Overall, these results indicate that ITC cells are involved in the expression of extinction.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)