Recruitment and inhibitory action of hippocampal axo-axonic cells during behavior
The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the “chandelier” or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting the initial segment, their in vivo activity p...
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Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2021-12, Vol.109 (23), p.3838-3850.e8 |
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Zusammenfassung: | The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the “chandelier” or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting the initial segment, their in vivo activity patterns and influence over pyramidal cell dynamics are not well understood. We achieved cell-type-specific genetic access to AACs in mice and show that AACs in the hippocampal area CA1 are synchronously activated by episodes of locomotion or whisking during rest. Bidirectional intervention experiments in head-restrained mice performing a random foraging task revealed that AACs inhibit CA1 pyramidal cells, indicating that the effect of GABA on the initial segments in the hippocampus is inhibitory in vivo. Finally, optogenetic inhibition of AACs at specific track locations induced remapping of pyramidal cell place fields. These results demonstrate brain-state-specific dynamics of a critical inhibitory controller of cortical circuits.
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•CA1 axo-axonic cells (AACs) are selectively labeled in Unc5b-2A-CreERT2 mice•AACs are activated by locomotion or whisking in awake mice•AACs exert inhibitory postsynaptic effects on CA1 pyramidal cells in vivo•AAC optogenetic silencing induces novel place fields in pyramidal cells
Dudok et al. introduce a transgenic mouse line for selectively labeling hippocampal axo-axonic cells (AACs). AACs are activated by movements in awake, behaving mice and exert inhibitory postsynaptic effects on CA1 pyramidal cells. During a spatial navigation task, location-specific AAC silencing induces novel place fields in pyramidal cells. |
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ISSN: | 0896-6273 1097-4199 1097-4199 |
DOI: | 10.1016/j.neuron.2021.09.033 |