AMYGDALA INTERNEURON · Characterisation of GABAergic interneurons in the amygdala of GAD65-GFP transgenic mice

Final Activity Report Summary - AMYGDALA INTERNEURON (Characterisation of GABAergic interneurons in the amygdala of GAD65-GFP transgenic mice)

I studied GABAergic synaptic transmission in a brain area, such as the amygdala, which is important for post-traumatic stress disorders. At chemical inhibitory synapses, the transmitter GABA is released from the nerve terminal, diffuses across the synaptic cleft and binds to GABA-A receptors of the postsynaptic membrane. Useful medicines selectively interact with GABA-A receptors and therefore their study is of considerable clinical interest. GABAergic medial paracapsular intercalated neurons (Imp) of amygdala are thought of playing a central role in fear extinction. My work reports novel insights into their synaptic organisation. I discovered that the pairs of synaptically-coupled intercalated neurons exhibit three distinct short-term synaptic responses, such as facilitating, depressing and constant, as a function of the frequency of stimulation of the presynaptic cells. These differences are linked to differences in presynaptic release probabilities and also to specialisations in the dendritic and axonal patterns of different cell pairs. I propose that the diverse functional connectivity of Imp neurons is required to maintain the stability of firing patterns which is critical for the computational role of the amygdala in fear extinction a mechanism of great clinical importance in humans. It is well known that different synapses of the mammalian brain have different synaptic strengths. This heterogeneity offers a computational advantage compared to equal synaptic weights in all synapses, because it provides a large dynamic range of action. At the population level, one can imagine that synapses with heterogeneous synaptic strengths can contribute to maintain stability of firing rates in the cellular network. (objective 1, 2, 3). In order to more accurately define the anatomy of Imp neurones, in a subsequent set of experiments, in collaboration with Prof. Francesco Ferraguti, we have evaluated how the diverse anatomical features correlate with the heterogeneous short-term synaptic plasticity observed amongst Imp cells (objective 4). In conclusion, a theoretical model in which the strengths of inhibitory synapses in a central pattern-generating circuit is dependent on activity-dependent plasticity has been proposed in the literature. My results represent the experimental demonstration of such theoretical model and may also lead to elucidate the mechanisms of action for widely used drugs such as anxiolytics.

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