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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Available from: Denis Paré, Oct 02, 2015
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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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    ABSTRACT: The amygdala has traditionally been associated with fear, mediating the impact of negative emotions on memory. However, this view does not fully encapsulate the function of the amygdala, nor the impact that processing in this structure has on the motivational limbic corticostriatal circuitry of which it is an important structure. Here we discuss the interactions between different amygdala nuclei with cortical and striatal regions involved in motivation; interconnections and parallel circuitries that have become increasingly understood in recent years. We review the evidence that the amygdala stores memories that allow initially motivationally neutral stimuli to become associated through pavlovian conditioning with motivationally relevant outcomes which, importantly, can be either appetitive (e.g. food) or aversive (e.g. electric shock). We also consider how different psychological processes supported by the amygdala such as conditioned reinforcement and punishment, conditioned motivation and suppression, and conditioned approach and avoidance behavior, are not only psychologically but also neurobiologically dissociable, being mediated by distinct yet overlapping neural circuits within the limbic corticostriatal circuitry. Clearly the role of the amygdala goes beyond encoding aversive stimuli to also encode the appetitive, requiring an appreciation of the amygdala's mediation of both appetitive and fearful behavior through diverse psychological processes.
    Frontiers in Behavioral Neuroscience 12/2013; 7:190. DOI:10.3389/fnbeh.2013.00190 · 3.27 Impact Factor
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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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    ABSTRACT: The acquisition and expression of conditioned fear depends on prefrontal-amygdala circuits. Auditory fear conditioning increases the tone responses of lateral amygdala (LA) neurons, but the increase is transient, lasting only a few hundred milliseconds after tone onset. It was recently reported that that the prelimbic (PL) prefrontal cortex transforms transient LA input into a sustained PL output, which could drive fear responses via projections to the lateral division of basal amygdala (BL). To explore the possible mechanisms involved in this transformation, we developed a large-scale biophysical model of the BL-PL network, consisting of 850 conductance-based Hodgkin-Huxley type cells, calcium-based learning, and neuromodulator effects. The model predicts that sustained firing in PL can be derived from BL-induced release of dopamine and norepinephrine that is maintained by PL-BL interconnections. These predictions were confirmed with physiological recordings from PL neurons during fear conditioning with the selective β-blocker propranolol and by inactivation of BL with muscimol. Our model suggests that PL has a higher bandwidth than BL, due to PL's decreased internal inhibition and lower spiking thresholds. It also suggests that variations in specific micro-circuits in the PL-BL interconnection can have a significant impact on the expression of fear, possibly explaining individual variability in fear responses. The human homologue of PL could thus be an effective target for anxiety disorders.
    Journal of Neurophysiology 05/2013; 110(4). DOI:10.1152/jn.00961.2012 · 2.89 Impact Factor
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    • "In summary, the available data suggest a prominent role of Imp cells of amygdala in fear learning, and the α2 and/or α3 subunit of GABA A receptors appears to be a novel molecular target for anxiolytic drugs (Likhtik et al., 2008; Rudolph and Knoflach, 2011). Therefore, we aimed to define whether these subunit-containing GABA A receptors are functionally present at synapses between Imp neurons. "
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