Structure and function of axo-axonic inhibition.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
01 12 2021
Historique:
received: 09 09 2021
accepted: 30 11 2021
pubmed: 2 12 2021
medline: 22 1 2022
entrez: 1 12 2021
Statut: epublish

Résumé

Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.

Identifiants

pubmed: 34851292
doi: 10.7554/eLife.73783
pii: 73783
pmc: PMC8758143
doi:
pii:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIMH NIH HHS
ID : RF1 MH123400
Pays : United States
Organisme : NINDS NIH HHS
ID : U19 NS104648
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY027036
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH114824
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104926
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1MH117815
Pays : United States

Informations de copyright

© 2021, Schneider-Mizell et al.

Déclaration de conflit d'intérêts

CS, AB, FC, DB, AB, SD, NT, KL, RL, JW, JZ, AN, BH, JB, MT, RT, GM, DB, YL, TC, NK, WS, DI, JZ, AZ, IT, SP, WW, MC, CJ, EF, LB, SS, CA, RR, NC No competing interests declared, TM discloses financial interests in Zetta AI LLC, JR, AT discloses financial interests in Vathes LLC, HS discloses financial interests in Zetta AI

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Auteurs

Casey M Schneider-Mizell (CM)

Allen Institute for Brain Sciences, Seattle, United States.

Agnes L Bodor (AL)

Allen Institute for Brain Sciences, Seattle, United States.

Forrest Collman (F)

Allen Institute for Brain Sciences, Seattle, United States.

Derrick Brittain (D)

Allen Institute for Brain Sciences, Seattle, United States.

Adam Bleckert (A)

Allen Institute for Brain Sciences, Seattle, United States.

Sven Dorkenwald (S)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Computer Science Department, Princeton University, Princeton, United States.

Nicholas L Turner (NL)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Computer Science Department, Princeton University, Princeton, United States.

Thomas Macrina (T)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Computer Science Department, Princeton University, Princeton, United States.

Kisuk Lee (K)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, United States.

Ran Lu (R)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Jingpeng Wu (J)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Jun Zhuang (J)

Allen Institute for Brain Sciences, Seattle, United States.

Anirban Nandi (A)

Allen Institute for Brain Sciences, Seattle, United States.

Brian Hu (B)

Allen Institute for Brain Sciences, Seattle, United States.

JoAnn Buchanan (J)

Allen Institute for Brain Sciences, Seattle, United States.

Marc M Takeno (MM)

Allen Institute for Brain Sciences, Seattle, United States.

Russel Torres (R)

Allen Institute for Brain Sciences, Seattle, United States.

Gayathri Mahalingam (G)

Allen Institute for Brain Sciences, Seattle, United States.

Daniel J Bumbarger (DJ)

Allen Institute for Brain Sciences, Seattle, United States.

Yang Li (Y)

Allen Institute for Brain Sciences, Seattle, United States.

Thomas Chartrand (T)

Allen Institute for Brain Sciences, Seattle, United States.

Nico Kemnitz (N)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

William M Silversmith (WM)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Dodam Ih (D)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Jonathan Zung (J)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Aleksandar Zlateski (A)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Ignacio Tartavull (I)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Sergiy Popovych (S)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Computer Science Department, Princeton University, Princeton, United States.

William Wong (W)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Manuel Castro (M)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Chris S Jordan (CS)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.

Emmanouil Froudarakis (E)

Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, United States.

Lynne Becker (L)

Allen Institute for Brain Sciences, Seattle, United States.

Shelby Suckow (S)

Allen Institute for Brain Sciences, Seattle, United States.

Jacob Reimer (J)

Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, United States.

Andreas S Tolias (AS)

Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, United States.
Department of Electrical and Computer Engineering, Rice University, Houston, United States.

Costas A Anastassiou (CA)

Allen Institute for Brain Sciences, Seattle, United States.
Department of Neurology, University of British Columbia, Vancouver, Canada.

H Sebastian Seung (HS)

Princeton Neuroscience Institute, Princeton University, Princeton, United States.
Computer Science Department, Princeton University, Princeton, United States.

R Clay Reid (RC)

Allen Institute for Brain Sciences, Seattle, United States.

Nuno Maçarico da Costa (NMD)

Allen Institute for Brain Sciences, Seattle, United States.

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