Computational Modeling of Lateral Amygdala Neurons During Acquisition and Extinction of Conditioned Fear, Using Hebbian Learning

摘要

The amygdaloid complex located within the medial temporal lobe plays an important role in the acquisition and expression of learned fear associations (Quirk et al. 2003) and contains three main components: the lateral nucleus (LA), the basal nucleus (BLA), and the central nucleus (CE) (Faber and Sah, 2002). The lateral nucleus of the amygdala (LA) is widely accepted to be a key site of plastic synaptic events that contributes to fear learning (Pare, Quirk, LeDoux, 2004). There are two main types of neurons within the LA and the BLA: principal pyramidal-like cells which form projection neurons and are glutamatergic and local circuit GABAergic interneurons (Faber and Sah, 2002). In auditory fear conditioning, convergence of tone [conditioned stimulus (CS)] and foot-shock [unconditioned stimulus (US)] inputs potentiates the synaptic transmission containing CS information from the thalamus and cortex to LA, which leads to larger responses in LA in the presentation of subsequent tones only. The increasing LA responses disinhibit the CE neurons via the intercalated (ITC) cells, eliciting fear responses via excessive projections to brain stem and hypothalamic sites (Pare, Quirk, LeDoux, 2004). As a result, rats learn to freeze to a tone that predicts a foot-shock. Once acquired, conditioned fear associations are not always expressed and repeated presentation of the tone CS in the absence of US causes conditioned fear responses to rapidly diminish, a phenomenon termed fear extinction (Quirk et al. 2003). Extinction does not erase the CS-US association, instead it forms a new memory that inhibits conditioned response (Quirk et al. 2003). To investigate the underlying mechanisms of fear acquisition and extinction in the LA, a two-neuron model consisting of one pyramidal cell and one GABAergic interneuron is developed, using Hodgkin-Huxley formulations with each containing two compartments, soma and the major dendrite. The firing patterns of the single pyramidal cell model matches those recorded from LA pyramidal neurons in vitro. Hebbian learning is implemented in the AMPA/NMDA channels in both the pyramidal cell and interneuron to model synaptic plasticity. Using the network model, we have show that LA can by itself learn both fear and extinction given that the pyramidal cell learns faster than the interneuron and the initial weight of the tone synapse of the pyramidal cell is higher than that of the interneuron. We have also shown that the fear memory is not erased by extinction and the inhibition of interneuron on pyramidal cell could play a key role in extinction. This raises the possibility that the fear memory is stored in the pyramidal cell while the extinction memory may be stored in the interneuron in LA, which is a result of the intrinsic firing properties of these two types of neurons.