Depolarizing effect of neocortical chandelier neurons
Open accessAbstract
Chandelier (or axo-axonic) cells are one of the most distinctive types of GABAergic interneurons in the cortex. Although they have traditionally been considered inhibitory neurons, data from rat and human neocortical preparations suggest that chandelier cells have a depolarizing effect on pyramidal neurons at resting membrane potential, and could even activate synaptic chains of neurons. At the same time, recent results from rat hippocampal chandeliers indicate a predominantly inhibitory effect on their postsynaptic targets. To better understand the function of chandelier neurons, we generated Nkx2.1Cre MADM mice, a strain of genetically engineered animals that, by expressing GFP in a subset of neocortical interneurons, enable the identification and targeting of chandelier cells in living brain slices. Using these mice, we characterized the basic electrophysiological properties of a homogeneous population of chandelier neurons from upper layers of somatosensory cortical slices. These chandelier cells have characteristic axon cartridges and stereotypical electrophysiological features, distinguishable from basket cells. To investigate the effect of chandelier cells on target neurons, we performed paired recordings from chandeliers and postsynaptic pyramidal cells. In both perforated patch and cell-attached configurations, chandelier PSPs have in every case a reversal potential that is depolarized from rest. Our results support the idea that chandelier cells depolarize pyramidal neurons and could potentially have an excitatory effect on the network at rest.
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Axo-axonic/chandelier cells are also considered fast spiking, although some intrinsic electrophysiological differences from PV basket cells have been reported.
“Axo-axonic or chandelier cells are also considered fast spiking, although some differences in intrinsic electrophysiological properties with PV basket cells have been reported”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Woodruff et al., 2009
Both hippocampal and neocortical AACs have origins in the medial ganglionic eminence (MGE) with specification driven by the homeodomain transcription factor Nkx2.1.
“Both hippocampal and neocortical AACs have origins in MGE with specification driven by the homeodomain transcription factor Nkx2.1 (1097, 1137, 1218).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1218]
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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes
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Altered Cortical GABA Neurotransmission in Schizophrenia: Insights into Novel Therapeutic Strategies
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Diversity of GABAergic Interneurons in Layer VIa and VIb of Mouse Barrel Cortex
Perrenoud, Q., Rossier, J., Geoffroy, H., Vitalis, T., & Gallopin, T. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs032 · Cited by 60 · see citing works
Statistical analysis and data mining of digital reconstructions of dendritic morphologies
Polavaram, S., Gillette, T. A., Parekh, R., & Ascoli, G. A. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00138 · Cited by 61 · see citing works
Cossart, R. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.10.003 · Cited by 60 · see citing works
Theoretical relation between axon initial segment geometry and excitability
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Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment
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Parvalbumin and parvalbumin chandelier interneurons in autism and other psychiatric disorders
Juárez, P., & Martínez‐Cerdeño, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.913550 · Cited by 55 · see citing works
A cortical sparse distributed coding model linking mini- and macrocolumn-scale functionality
Rinkus, G. J. (2010) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2010.00017 · Cited by 55 · see citing works
Jeevakumar, V., & Kroener, S. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhu293 · Cited by 58 · see citing works
Interneuron development and dysfunction
Yang, J., Yang, X. W., & Tang, K. (2021) · FEBS Journal · doi:10.1111/febs.15872 · Cited by 52 · see citing works
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Spatial and Temporal Dynamics in the Ionic Driving Force for GABAAReceptors
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Chloride homeostasis and GABA signaling in temporal lobe epilepsy
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Subgroups of parvalbumin-expressing interneurons in layers 2/3 of the visual cortex
Helm, J. S., Akgül, G., & Wollmuth, L. P. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00782.2012 · Cited by 43 · see citing works
Linking neuronal lineage and wiring specificity
Li, H., Shuster, S. A., Li, J., & Luo, L. (2018) · Neural Development · doi:10.1186/s13064-018-0102-0 · Cited by 41 · see citing works
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Spatial distribution of neurons innervated by chandelier cells
Blázquez‐Llorca, L., Woodruff, A. R., Inan, M., Anderson, S. A., Yuste, R., DeFelipe, J., & Merchán-Pérez, Á. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0828-3 · Cited by 36 · see citing works
Self-citationCl-out is a novel cooperative optogenetic tool for extruding chloride from neurons
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Chandelier Cells in Functional and Dysfunctional Neural Circuits
Wang, Y., Zhang, P., & Wyskiel, D. R. (2016) · Frontiers in Neural Circuits · doi:10.3389/fncir.2016.00033 · Cited by 37 · see citing works
Chandelier cell anatomy and function reveal a variably distributed but common signalPreprint
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Westerholz, S., de Lima, A. D., & Voigt, T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00121 · Cited by 33 · see citing works
Enrichment of GABAA Receptor α-Subunits on the Axonal Initial Segment Shows Regional Differences
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Classification of neocortical interneurons using affinity propagation
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Genetically encoded sensors for Chloride concentration
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Synaptic gating at axonal branches, and sharp‐wave ripples with replay: a simulation study
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Abnormal GABAergic Function and Negative Affect in Schizophrenia
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Transplantation of GABAergic interneurons for cell-based therapy
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- Authors
- Woodruff, A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Woodruff, Alan
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2009
- Volume
- 3
- Pages
- 15-15
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC2769545
- OpenAlex
- W2156874940
- Cited by
- 163
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 1 · 2018: 9 · 2017: 8 · 2016: 16 · 2015: 2 · 2014: 14 · 2013: 21 · 2012: 16
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- other-oa
- Locations
- Frontiers in Neural Circuits (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- National Institute of Mental Health (MH066912, K02MH070031, R01MH066912, MH070031)
- National Eye Institute (EY-11787, R01EY011787)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- chandelier cells, neocortex, pyramidal neurons, GABAergic interneurons, synaptic inhibition, somatosensory cortex, paired recordings, basket cells
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