Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells

Lu, Juan; Tucciarone, Jason; Padilla-Coreano, Nancy; He, Miao; Gordon, Joshua A.; Huang, Z. Josh

doi:10.1038/nn.4624

Cited by 103 publications

(161 citation statements)

References 56 publications

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“…Consistent with this observation, activation of the ChC population in vivo has diverse effects on nearby PyCs, from strong inhibition to no response (Lu et al, 2017), despite nearly all PyCs likely receiving ChC input (Inan et al, 2013). The logic underlying this variability, and thus the heterogeneity of ChC influence on the downstream targets, is largely unknown, although categorical differences in long-range projection targets are one potential factor (Lu et al, 2017). A second reason is functional.…”

Section: Introductionmentioning

confidence: 76%

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

Schneider-Mizell

Collman

et al. 2020

Preprint

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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.

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Section: Introductionmentioning

confidence: 76%

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

Schneider-Mizell

Collman

et al. 2020

Preprint

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“…Firing of pvBCs coordinates synchrony of neuronal networks in the cortex (Hu H and P Jonas 2014;Lu J et al 2017;Cardin JA 2018). Through robust autapses, pvBCs adjust their temporal firing interval and correspondingly set inhibition in their target neurons.…”

Section: Discussionmentioning

confidence: 99%

Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex

Szegedi

Paizs

Baka

et al. 2019

Preprint

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Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron types is poorly known. We investigated GABAergic parvalbumin-expressing basket cells (pvBCs) in layer 2/3 (L2/3) in mice as well as in human neocortical tissue resected in deep-brain surgery. Most pvBCs showed robust GABAAR-mediated self-innervation in both species, but autapses were rare in nonfast spiking GABAergic interneurons. Light-and electron microscopy analyses revealed pvBC axons innervating their own soma and proximal dendrites. GABAergic selfinhibition conductance was similar in human and mouse pvBCs and comparable to that of synapses from pvBCs to other L2/3 neurons. Autaptic conductance prolonged somatic inhibition in pvBCs after a spike and inhibited repetitive firing. Perisomatic autaptic inhibition has evolved in pvBCs of various cortical layers and different mammalian species to control discharge of these interneurons.

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“…AIS-colocalized cartridges and presynaptic boutons were quantified, as off-target varicosities lack presynaptic markers and symmetric synaptic densities (55). The AIS was immunolabeled by an anti-phospho-IκB antibody (pIκB) (50,51,53,56), which strongly correlates with the AIS labeled by ankyrin-G antibodies in the mouse neocortex (57)( Figure S2). Quantification was performed in a double-blinded fashion to avoid experimenters' bias.…”

Section: Loss Of Dscam Impairs Chc Presynaptic Development In Micementioning

confidence: 99%

Dscamgene triplication causes neocortical overinhibition in Down syndrome

Liu

Caballero‐Florán

Yang

et al. 2020

Preprint

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A growing number of molecules have been identified as regulators of inhibitory synapse development, but whether dysregulated expression of these molecules contribute to brain disorders is poorly understood. Here we show that Down syndrome cell adhesion molecule (Dscam) regulates the inhibition of neocortical pyramidal neurons (PyNs) in a level-dependent fashion. Loss of Dscam impairs inhibitory neuron development and function.In the Ts65Dn mouse model for Down syndrome, where Dscam is overexpressed, GABAergic innervation of cortical PyNs by chandelier and basket cells is increased. Genetic normalization of Dscam expression rescues the excessive GABAergic innervation and the increased inhibition of PyNs. These findings demonstrate excessive GABAergic innervation and inhibition in the neocortex of Down syndrome mouse model and identify Dscam overexpression as the cause. They also implicate dysregulated Dscam levels as a potential pathogenic driver in related neurological disorders. Dscam| Down syndrome| GABAergic| synapse| chandelier cells| basket cells| Neocortex| Ts65Dn

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Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells

Cited by 103 publications

References 56 publications

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

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

Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex

Dscamgene triplication causes neocortical overinhibition in Down syndrome

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