Impact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling study

Department of Psychology, Cornell University, Ithaca, New York 14850, USA.
Learning & memory (Cold Spring Harbor, N.Y.) (Impact Factor: 3.66). 03/2011; 18(4):226-40. DOI: 10.1101/lm.1938011
Source: PubMed


Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce neurons to BLA inputs. These effects were hypothesized to result from the activation of ITC cells projecting to Ce. However, ITC cells inhibit each other, leading to the question of how IL inputs could overcome the inter-ITC inhibition to regulate the responses of Ce neurons to aversive conditioned stimuli (CSs). To investigate this, we first developed a compartmental model of a single ITC cell that could reproduce their bistable electroresponsive properties, as observed experimentally. Next, we generated an ITC network that implemented the experimentally observed short-term synaptic plasticity of inhibitory inter-ITC connections. Model experiments showed that strongly adaptive CS-related BLA inputs elicited persistent responses in ITC cells despite the presence of inhibitory interconnections. The sustained CS-evoked activity of ITC cells resulted from an unusual slowly deinactivating K(+) current. Finally, over a wide range of stimulation strengths, brief IL activation caused a marked increase in the firing rate of ITC neurons, leading to a persistent decrease in Ce output, despite inter-ITC inhibition. Simulations revealed that this effect depended on the bistable properties and synaptic heterogeneity of ITC neurons. These results support the notion that IL inputs are in a strategic position to control extinction of conditioned fear via the activation of ITC neurons.

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    • "However, the projections from the PL and IL have distinct effects on amygdala activity and may provide a potential mechanism for balancing the impact of an explicit CS-US association stored in the BLA and the more general excitation evoked by a stimulus maintained by CeN circuitry. Excitatory inputs from the PL project directly onto the BLA (Cassell and Wright, 1986; Vertes, 2004), enhancing BLA activity and BLA-mediated inhibition of CeN outputs (Burgos-Robles et al., 2009) whereas excitatory inputs from the IL to intercalated cells (ITC) between the BLA and CeN (Cassell and Wright, 1986) disinhibit CeN activity modulated by the BLA (Quirk et al., 2003; Li et al., 2011a). "
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    • "Both soma and dendritic compartments had the following currents: I L , I Na , I DR , persistent muscarinic, and I Ca . In addition to these, the dendrite had the following currents: I KCa , slow apamininsensitive , voltage-independent afterhyperpolarization channel, I D , and I H (same as in Li et al. 2011). For the Ce lateral (CeL) neurons, we used a modified version of the regular spiking CeM cell, with the same passive properties above, except for E L which was Ϫ70 mV. "
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