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Authors & Affiliations
Clara Lenherr, Juan Burrone
Abstract
During cortical development, GABAergic interneurons refine their connectivity in response to changes in activity of their postsynaptic targets, contributing to the establishment of functional neural circuits. Parvalbumin-expressing chandelier cells, a GABAergic interneuron subtype that forms axo-axonic synapses at the axon-initial segment (AIS) of pyramidal neurons, are optimally positioned to regulate network-wide spiking activity. It has been shown that chandelier cells change the number and density of their axon-targeting synapses onto L2/3 pyramidal neurons following chronic changes in network activity during postnatal development in mice. However, it remains unknown whether chandelier cells respond to altered activity of single postsynaptic neurons. Here, we aim to establish the spatial sensitivity of axo-axonic synapses by altering pyramidal cell activity across different spatial scales: from whole networks to single cells. Taking advantage of FLP-FRT recombination, viral delivery of a Flp-dependent excitatory chemogenetic receptor (hM3Dq) and high or low concentrations of Flippase enabled network-wide or sparse expression of hM3Dq. Immediate early gene staining confirmed that CNO treatment caused either network-wide or selective activation of sparse hM3Dq-expressing cells. We found that, in agreement with previous work from the lab, network-wide increases in activity over two days during postnatal development (P16-18) caused a significant reduction in axo-axonic synapse number at the AIS. Importantly, increasing activity in single neurons also resulted in a decrease in axo-axonic synapses in hyperactivated, but not neighbouring cells within the network. We therefore propose that axo-axonic synapses show a highly sensitive spatial resolution that can sense the activity levels of single postsynaptic pyramidal neurons.