Schreiber WB, Keller S, Knox D (2014) The role of the basal forebrain cholinergic neurons in cued extinction memory. Neuroscience 2014 Abstracts 748.01. Society for Neuroscience, Washington, DC.
Summary: Fear extinction learning and memory requires inhibition of neural activity in amygdala (AMY) nuclei driven by neural substrates in the ventromedial prefrontal cortex (vmPFC), resulting in the behavioral phenotype of a decreased fear response (e.g. low levels of conditioned freezing). Fear extinction memory retrieval is sensitive to contextual feature manipulations, rendering extinction memory retrieval sensitive to hippocampal (HIPP) input to the AMY. Function of the vmPFC and HIPP requires cholinergic innervation from basal forebrain cholinergic neurons (BFCNs), including neurons in the nucleus basalis (NB), horizontal diagonal band of Broca (hDBB), vertical diagonal band of Broca (vDBB), and medial septum (MS). Given the importance of the vmPFC and HIPP for extinction memory, we hypothesized that intact BFCNs would be critical for extinction memory. We found that complete BFCN lesions using 192 IgG-saporin disrupted acquisition of cued fear extinction memory (Experiment 1). Follow-up studies examining more restrictive cholinergic lesions of the MS/vDBB (Experiment 2) or the NB/hDBB (Experiment 3) suggest these two clusters of BFCNs may differentially modulate acquisition and retention of cued extinction memory. The overall results of this study suggest that BFCNs are a component of the fear extinction circuit and a potential target for the pharmacological treatment of psychological disorders thought to stem from extinction memory deficits (e.g. PTSD).
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