The Synaptic Organization of Layer 6 Circuits Reveals Inhibition as a Major Output of a Neocortical Sublamina
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The canonical cortical microcircuit has principally been defined by interlaminar excitatory connections among the six layers of the neocortex. However, excitatory neurons in layer 6 (L6), a layer whose functional organization is poorly understood, form relatively rare synaptic connections with other cortical excitatory neurons. Here, we show that the vast majority of parvalbumin inhibitory neurons in a sublamina within L6 send axons through the cortical layers toward the pia. These interlaminar inhibitory neurons receive local synaptic inputs from both major types of L6 excitatory neurons and receive stronger input from thalamocortical afferents than do neighboring pyramidal neurons. The distribution of these interlaminar interneurons and their synaptic connectivity further support a functional subdivision within the standard six layers of the cortex. Positioned to integrate local and long-distance inputs in this sublayer, these interneurons generate an inhibitory interlaminar output. These findings call for a revision to the canonical cortical microcircuit.
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The interlaminar or translaminar projections of these Pvalb met-types resemble projections previously reported for layer 6 fast-spiking neurons.
“These interlaminar or translaminar projections resemble those described previously for fast-spiking neurons in L6 (Frandolig et al., 2019; Bortone et al., 2014).”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Frandolig et al., 2019
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Motor Control of Distinct Layer 6 Corticothalamic Feedback Circuits
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Complementary Organization of Mouse Driver and Modulator Cortico-thalamo-cortical Circuits
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The Interneuron Class Struggle
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Layer 6 is a hub for cholinergic modulation in the mouse auditory cortex
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Correlated Somatosensory Input in Parvalbumin/Pyramidal Cells in Mouse Motor Cortex
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Homeostatic regulation of neuronal excitability by probiotics in male germ‐free mice
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Layered Structure of Cortex Explains Reversal Dynamics in Bistable PerceptionPreprint
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Uncovering network mechanism underlying thalamic deep brain stimulationPreprint
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Intercellular communication in the brain via dendritic nanotubular networkPreprint
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Layer 6 Corticothalamic Neurons in the Somatosensory System
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Self-citationVisual field specializations in mouse dLGNPreprint
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Effects of corticothalamic feedback depend on visual responsiveness and stimulus type
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Self-citationDeviance detection via competitive inhibition between local neocortical ensembles
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GABAergic interneurons in local circuits of primate prefrontal cortex
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- Authors
- Frandolig, J. E., Matney, C. J., Lee, K., Kim, J., Chevée, M., Kim, S.-J., Bickert, A. A., & Brown, S. P.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Brown, Solange Pezon
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 28
- Issue
- 12
- Pages
- 3131-3143.e5
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6941480
- OpenAlex
- W2974656325
- Cited by
- 78
- References
- 107
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 18 · 2020: 13 · 2019: 1
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (1656592)
- Johns Hopkins University
- National Institute of Neurological Disorders and Stroke (P30NS050274)
- National Research Foundation of Korea (NRF-2011-357-E00005)
- Center for Outcomes Research and Evaluation, Yale School of Medicine
- Boehringer Ingelheim
- Boehringer Ingelheim Fonds
- Esther A. and Joseph Klingenstein Fund
- Office of the Provost, Johns Hopkins University
- National Institutes of Health (5T32EY017203)
- 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 › Visual perception and processing mechanisms
- Keywords
- layer 6, neocortex, parvalbumin interneurons, cortical microcircuits, thalamocortical afferents, pyramidal neurons, synaptic connectivity
- MeSH terms
- Animals, Interneurons, Mice, Transgenic, Neural Inhibition, Synapses, Pyramidal Cells, Neocortex, Mice
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