Chandelier cell anatomy and function reveal a variably distributed but common signal

Abstract

The activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activity in vivo was highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.

Connectomes across development reveal principles of brain maturation

“…Moreover, multiple animals need to be analyzed to assess structural and behavioural heterogeneity. Serial-section electron microscopy (EM) allows reconstruction of neural circuits with synapse resolution [14][15][16][17][18][19][20] , but low throughput makes it difficult to compare whole brain samples and comprehensively assess plasticity. EM has been applied to assess wiring differences between species 21 , sexes 22 , genotypes 23 , and ages 4,24 .…”

Multiscale and multimodal reconstruction of cortical structure and function

“…The present paper complements two companion reports (Dorkenwald et al ., 2019; Schneider-Mizell et al ., 2020) that apply this resource to address specific scientific questions. The present work fully describes the resource, and showcases its usefulness through a broad range of scientific analyses.…”

Multi-modal characterization and simulation of human epileptic circuitry

“…To generate human GC single-neuron models we used a 3-stage approach leveraging a genetic optimization framework which relies on comparisons between experimental and model electrophysiology features for a particular morphology reconstruction ( Fig. S4, (25)(26)(27)). Using this optimization framework, we generated GC models accounting for active ionic conductances along their entire soma, axonal and dendritic arbor.…”