Chrna2-Martinotti cells synchronize layer 5 type A pyramidal cells via rebound excitation
Open accessAbstract
Martinotti cells are the most prominent distal dendrite-targeting interneurons in the cortex, but their role in controlling pyramidal cell (PC) activity is largely unknown. Here, we show that the nicotinic acetylcholine receptor α2 subunit (Chrna2) specifically marks layer 5 (L5) Martinotti cells projecting to layer 1. Furthermore, we confirm that Chrna2-expressing Martinotti cells selectively target L5 thick-tufted type A PCs but not thin-tufted type B PCs. Using optogenetic activation and inhibition, we demonstrate how Chrna2-Martinotti cells robustly reset and synchronize type A PCs via slow rhythmic burst activity and rebound excitation. Moreover, using optical feedback inhibition, in which PC spikes controlled the firing of surrounding Chrna2-Martinotti cells, we found that neighboring PC spike trains became synchronized by Martinotti cell inhibition. Together, our results show that L5 Martinotti cells participate in defined cortical circuits and can synchronize PCs in a frequency-dependent manner. These findings suggest that Martinotti cells are pivotal for coordinated PC activity, which is involved in cortical information processing and cognitive control.
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SST+ Martinotti cells are transcriptionally heterogeneous and have an ascending axon that arborizes profusely in layer 1.
“SST+ Martinotti cells constitute a transcriptionally heterogeneous group of interneurons characterized by an ascending axon that arborizes profusely in layer 1”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Hilscher et al., 2017
In mPFC of Chrna2-Cre mice, 90.61±4.210% (n=6 mice) of Chrna2-Cre+ cells show SST immunoreactivity.
“To selectively manipulate LTS-SST interneurons, we used Chrna2-Cre mice13 in which 90.61+/−4.210% (n=6 mice) of mPFC Chrna2-Cre+cells show SST immunoreactivity (Fig.6A).”
From A prefrontal–paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice (2020) · cites this paper as [13]
Chrna2+ LTS-SST interneurons selectively target deep-layer pyramidal neurons that typically project to sub-cortical targets but not callosal projection neurons or intratelencephalic neurons.
“Importantly, Chrna2+LTS-SST interneurons were previously shown to selectively target deep-layer pyramidal neurons that typically project to sub-cortical targets but not to callosal projection neurons or intratelencephalic neurons13; consistent with this finding, we observed no change in inhibitory drive in mPFC neurons projecting to the contralateral PFC (mPFC->cPFC) or nucleus accumbens (mPFC->NA”
From A prefrontal–paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice (2020) · cites this paper as [13]
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References 63 · Cited by 118
- Authors
- Hilscher, M. M., Leão, R. N., Edwards, S. J., Leão, K. E., & Kullander, K.
- Affiliations
- Uppsala University (SE)
- Universidade Federal do Rio Grande do Norte (BR)
- Corresponding author
- Hilscher, Markus M.
- Kullander, Klas
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-02-09
- Volume
- 15
- Issue
- 2
- Pages
- e2001392
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC5300109
- OpenAlex
- W2586597606
- Cited by
- 118
- References
- 63
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 11 · 2023: 21 · 2022: 14 · 2021: 9 · 2020: 11 · 2019: 13 · 2018: 15 · 2017: 6
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- American Tinnitus Association
- Swedish Foundation for International Cooperation in Research and Higher Education
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Governo Brasil
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Vetenskapsrådet
- Division of Graduate Education
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- Martinotti cells, CHRNA2, nicotinic acetylcholine receptors, layer 5 pyramidal cells, rebound excitation, neuronal synchronization, cortical circuits, optogenetics, cognitive control
- MeSH terms
- Action Potentials, Animals, Female, Interneurons, Male, Mice, Transgenic, Receptors, Nicotinic, Time Factors, Pyramidal Cells, Cell Shape, Inhibitory Postsynaptic Potentials, Optogenetics
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