NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state

Katayun Cohen-Kashi Malina; Emmanouil Tsivourakis; Dahlia Kushinsky; Daniella Apelblat; Stav Shtiglitz; Eran Zohar; Michael Sokoletsky; Gen ichi Tasaka; Adi Mizrahi; Ilan Lampl; Ivo Spiegel

doi:10.1016/j.neuron.2021.05.001

NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state

Katayun Cohen-Kashi Malina, Emmanouil Tsivourakis, Dahlia Kushinsky, Daniella Apelblat, Stav Shtiglitz, Eran Zohar, Michael Sokoletsky, Gen ichi Tasaka, Adi Mizrahi, Ilan Lampl, Ivo Spiegel^*

^*Corresponding author for this work

Department of Neurobiology (Natural Sciences)

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Processing of sensory information in neural circuits is modulated by an animal's behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.

Original language	American English
Pages (from-to)	2150-2164.e5
Journal	Neuron
Volume	109
Issue number	13
DOIs	https://doi.org/10.1016/j.neuron.2021.05.001
State	Published - 7 Jul 2021

Bibliographical note

Funding Information:
We thank all the members of the Spiegel lab for comments and discussions; Shakked Ganor for assistance with animal husbandry; and Drs. Jackie Schiller (Technion, Haifa, Israel), Michal Rivlin, and Amos Arieli (Weizmann Institute of Science, Rehovot, Israel) for critical reading of the manuscript. We also thank Dr. Michal Rivlin for her help with establishing visual stimulation protocols. This work was supported by a Minna James Heineman grant ( 712566-01 to I.S.), an Israel Science Foundation (ISF) Israeli Centers for Research Excellence (I-CORE) grant ( 1916/12 to I.S.), a Deutsche Forschungsgemeinschaft (DFG)-Sonderforschungsbereiche (SFB) grant ( 1089 to I.L.), an ISF grant ( 1539/17 to I.L.), and a Minerva Foundation grant (to I.L.). I.S. is the incumbent of the Friends and Linda and Richard Price Career Development Chair and a scholar in the Zuckerman STEM leadership program.

Funding Information:
We thank all the members of the Spiegel lab for comments and discussions; Shakked Ganor for assistance with animal husbandry; and Drs. Jackie Schiller (Technion, Haifa, Israel), Michal Rivlin, and Amos Arieli (Weizmann Institute of Science, Rehovot, Israel) for critical reading of the manuscript. We also thank Dr. Michal Rivlin for her help with establishing visual stimulation protocols. This work was supported by a Minna James Heineman grant (712566-01 to I.S.), an Israel Science Foundation (ISF) Israeli Centers for Research Excellence (I-CORE) grant (1916/12 to I.S.), a Deutsche Forschungsgemeinschaft (DFG)-Sonderforschungsbereiche (SFB) grant (1089 to I.L.), an ISF grant (1539/17 to I.L.), and a Minerva Foundation grant (to I.L.). I.S. is the incumbent of the Friends and Linda and Richard Price Career Development Chair and a scholar in the Zuckerman STEM leadership program. K.C.-K.M. and I.S. initiated and conceived the project. Experiments and analyses were performed by K.C.-K.M. except as follows: all ex vivo recordings in acute slices were done by E.T.; rabies-tracing experiments were done by D.K. who also prepared key viral reagents and made essential contributions to 2P imaging; FISH in Figure S1 was done by D.A.; S.S. helped with 2P imaging experiments and their analyses; E.Z. cloned and tested the pAAV-hSyn-Flex-mRuby3 construct; M.S. and I.L. helped with initial 2P imaging and pupillometry experiments and with custom-written software to analyze these experiments (I.L. also helped with analyzing in vivo electrophysiology experiments); and G.T. and A.M. helped with establishing and quantifying the rabies-tracing experiments. I.S. supervised the project and acquired funding. K.C.-K.M. and I.S. wrote the manuscript with input and comments from all authors. The authors declare no competing interests.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

L1 NDNF interneurons
brain state
cortex
dendritic inhibition
gain modulation
layer 1
somatic disinhibition
stimulus selectivity
top-down processing
visual processing

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10.1016/j.neuron.2021.05.001

Cite this

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title = "NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state",

abstract = "Processing of sensory information in neural circuits is modulated by an animal's behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.",

keywords = "L1 NDNF interneurons, brain state, cortex, dendritic inhibition, gain modulation, layer 1, somatic disinhibition, stimulus selectivity, top-down processing, visual processing",

author = "{Cohen-Kashi Malina}, Katayun and Emmanouil Tsivourakis and Dahlia Kushinsky and Daniella Apelblat and Stav Shtiglitz and Eran Zohar and Michael Sokoletsky and Tasaka, {Gen ichi} and Adi Mizrahi and Ilan Lampl and Ivo Spiegel",

note = "Funding Information: We thank all the members of the Spiegel lab for comments and discussions; Shakked Ganor for assistance with animal husbandry; and Drs. Jackie Schiller (Technion, Haifa, Israel), Michal Rivlin, and Amos Arieli (Weizmann Institute of Science, Rehovot, Israel) for critical reading of the manuscript. We also thank Dr. Michal Rivlin for her help with establishing visual stimulation protocols. This work was supported by a Minna James Heineman grant ( 712566-01 to I.S.), an Israel Science Foundation (ISF) Israeli Centers for Research Excellence (I-CORE) grant ( 1916/12 to I.S.), a Deutsche Forschungsgemeinschaft (DFG)-Sonderforschungsbereiche (SFB) grant ( 1089 to I.L.), an ISF grant ( 1539/17 to I.L.), and a Minerva Foundation grant (to I.L.). I.S. is the incumbent of the Friends and Linda and Richard Price Career Development Chair and a scholar in the Zuckerman STEM leadership program. Funding Information: We thank all the members of the Spiegel lab for comments and discussions; Shakked Ganor for assistance with animal husbandry; and Drs. Jackie Schiller (Technion, Haifa, Israel), Michal Rivlin, and Amos Arieli (Weizmann Institute of Science, Rehovot, Israel) for critical reading of the manuscript. We also thank Dr. Michal Rivlin for her help with establishing visual stimulation protocols. This work was supported by a Minna James Heineman grant (712566-01 to I.S.), an Israel Science Foundation (ISF) Israeli Centers for Research Excellence (I-CORE) grant (1916/12 to I.S.), a Deutsche Forschungsgemeinschaft (DFG)-Sonderforschungsbereiche (SFB) grant (1089 to I.L.), an ISF grant (1539/17 to I.L.), and a Minerva Foundation grant (to I.L.). I.S. is the incumbent of the Friends and Linda and Richard Price Career Development Chair and a scholar in the Zuckerman STEM leadership program. K.C.-K.M. and I.S. initiated and conceived the project. Experiments and analyses were performed by K.C.-K.M. except as follows: all ex vivo recordings in acute slices were done by E.T.; rabies-tracing experiments were done by D.K. who also prepared key viral reagents and made essential contributions to 2P imaging; FISH in Figure S1 was done by D.A.; S.S. helped with 2P imaging experiments and their analyses; E.Z. cloned and tested the pAAV-hSyn-Flex-mRuby3 construct; M.S. and I.L. helped with initial 2P imaging and pupillometry experiments and with custom-written software to analyze these experiments (I.L. also helped with analyzing in vivo electrophysiology experiments); and G.T. and A.M. helped with establishing and quantifying the rabies-tracing experiments. I.S. supervised the project and acquired funding. K.C.-K.M. and I.S. wrote the manuscript with input and comments from all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

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doi = "10.1016/j.neuron.2021.05.001",

language = "American English",

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T1 - NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state

AU - Cohen-Kashi Malina, Katayun

AU - Tsivourakis, Emmanouil

AU - Kushinsky, Dahlia

AU - Apelblat, Daniella

AU - Shtiglitz, Stav

AU - Zohar, Eran

AU - Sokoletsky, Michael

AU - Tasaka, Gen ichi

AU - Mizrahi, Adi

AU - Lampl, Ilan

AU - Spiegel, Ivo

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PY - 2021/7/7

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N2 - Processing of sensory information in neural circuits is modulated by an animal's behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.

AB - Processing of sensory information in neural circuits is modulated by an animal's behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.

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KW - brain state

KW - cortex

KW - dendritic inhibition

KW - gain modulation

KW - layer 1

KW - somatic disinhibition

KW - stimulus selectivity

KW - top-down processing

KW - visual processing

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DO - 10.1016/j.neuron.2021.05.001

M3 - Article

C2 - 34038743

AN - SCOPUS:85108956865

SN - 0896-6273

VL - 109

SP - 2150-2164.e5

JO - Neuron

JF - Neuron

IS - 13

ER -

NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state

Abstract

Bibliographical note

Keywords

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