In Vivo Firing Patterns Of Chandelier Cells In The Medial Prefrontal Cortex

Neural network dynamics result from the interplay between excitation and inhibition.The γ-aminobutyric acid(GABA)interneurons which mediate synaptic inhibition,display remarkable diversity and complexity in terms of cell morphology,electrophysiology,plasticity,and connectivity.Therefore,to investigate the function of interneurons at single-cell type precision,we focused on chandelier cells,a specific GABAergic interneuron subtype that targets the axon initiation segments of excitatory pyramidal neurons.Utilizing in vivo multichannel recording and optogenetic identification,we identified and consistently recorded the in vivo firing activity of chandelier cells in layer II of the medial prefrontal cortex for a long time.By analyzing the in vivo firing pattern of chandelier cells,we explored their physiological functions.First,we accomplished the identification of chandelier cells at both morphological and optogenetic levels.The somas of the labeled chandelier cells were mostly distributed at the border between layer 1and layer 2 and targeted 53.2 ± 1.5% of the axon initiation segments within their axon spanning ranges.The morphological verification also revealed that the labeled chandelier cells constituted a relatively homogeneous population.In optogenetic identification experiments,we found that short-latency responses could be elicited in chandelier cells following high-frequency pulse stimulation.Their spontaneous firing sequence distribution had peak intervals between 15-25 ms,suggesting their capacity for rapid firing and significant potential in regulating the balance between excitation and inhibition.Second,the spontaneous firing sequences of chandelier cells exhibited phaselocking relationship with high-frequency oscillations in local field potentials.This modulation was restricted to the local field potentials within the regulatory ranges of chandelier cells,and no phase-locking relationship was observed with distant field potentials or hippocampal field potentials.When opto stimulated chandelier cells,we observed a significant decrease in the firing frequency of numerous pyramidal neurons.This finding implies that in vivo activation of chandelier cells exerts an inhibitory effect on local neural networks.Additionally,we investigated the firing patterns of chandelier cells across various behavioral states.When mice were in the home cage,the firing rate of chandelier cells remained stable at a low level during basal states.However,when mice were subjected to multiple behavioral experiments,the firing rate of chandelier cells significantly increased without displaying selectivity to a specific behavior.Compared to other interneurons recorded simultaneously,the chandelier cells exhibited a lower overall firing rate in any state and demonstrated a more refined activity pattern.These results suggest that chandelier cells exhibit behavioral state adaptations for neural network modulation.Lastly,we discovered a correlation between the firing activity of chandelier cells and the activity of population neurons.Regardless of the state of the mice,the firing rate of chandelier cells increased along with the firing rate of population neurons.This result indicates that chandelier cells may play a role in inhibiting the overexcitation of local neural networks.In conclusion,we elucidated the in vivo firing patterns of chandelier cells in medial prefrontal cortex during free activity in mice from the perspective of in vivo electrophysiology,and revealed their role in regulating the excitation-inhibition balance of neural networks.