Disynaptic Inhibition between Neocortical Pyramidal Cells Mediated by Martinotti Cells
Open accessAbstract
Reliable activation of inhibitory pathways is essential for maintaining the balance between excitation and inhibition during cortical activity. Little is known, however, about the activation of these pathways at the level of the local neocortical microcircuit. We report a disynaptic inhibitory pathway among neocortical pyramidal cells (PCs). Inhibitory responses were evoked in layer 5 PCs following stimulation of individual neighboring PCs with trains of action potentials. The probability for inhibition between PCs was more than twice that of direct excitation, and inhibitory responses increased as a function of rate and duration of presynaptic discharge. Simultaneous somatic and dendritic recordings indicated that inhibition originated from PC apical and tuft dendrites. Multineuron whole-cell recordings from PCs and interneurons combined with morphological reconstructions revealed the mediating interneurons as Martinotti cells. Martinotti cells received facilitating synapses from PCs and formed reliable inhibitory synapses onto dendrites of neighboring PCs. We describe this feedback pathway and propose it as a central mechanism for regulation of cortical activity.
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Facilitation onto Sst interneurons enables even a single high-frequency burst from one presynaptic cell to recruit them and produce feedback inhibition.
“the facilitation onto Sst INs enable even a single high frequency burst from one presynaptic cell to recruit Sst INs and produce feedback inhibition”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Silberberg and Markram, 2007
All Sst interneurons appear to have facilitating excitatory inputs and muscarinic-mediated depolarization.
“Despite these differences, all SST INs seem to have facilitating excitatory inputs and a muscarinic-mediated depolarization”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Silberberg and Markram, 2007
Martinotti cells have relatively heterogeneous firing patterns but often mediate disynaptic inhibition.
“Martinotti cells have relatively heterogenous firing patterns but they often mediate disynaptic inhibition”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Silberberg and Markram, 2007
SOM+ MCs in other layers receive facilitating excitatory inputs from local principal neurons in both S1 and V1.
“SOM+ MCs in other layers are known to receive facilitating excitatory inputs from local principal neurons in both S162,63 and V129,64.”
From Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas (2019) · cites this paper as [63]
A similar connectivity rule exists for SST-containing Martinotti cells in deep cortical layers, as they form circuits preferentially with neighboring subcerebral projecting PCs.
“A similar connectivity rule exists for SST-containing Martinotti cells in deep cortical layers, as they form circuits preferentially with neighboring subcerebral projecting PCs (647, 1015) (FIGURE 8C).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1015]
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References 64 · Cited by 768
- Authors
- Silberberg, G., & Markram, H.
- Affiliations
- Karolinska Institutet (SE)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Silberberg, Gilad
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 53
- Issue
- 5
- Pages
- 735-746
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1991762922
- Cited by
- 768
- References
- 64
- Citations by year
- 2026: 29 · 2025: 40 · 2024: 39 · 2023: 35 · 2022: 40 · 2021: 48 · 2020: 42 · 2019: 43 · 2018: 39 · 2017: 43 · 2016: 47 · 2015: 54 · 2014: 38 · 2013: 40 · 2012: 41
- FWCI
- 15.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2330 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Human Frontier Science Program
- European Commission
- 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
- disynaptic inhibition, Martinotti cells, neocortical pyramidal cells, layer 5 pyramidal cells, inhibitory microcircuits, dendritic inhibition, interneurons, excitation-inhibition balance, product inhibition
- MeSH terms
- Action Potentials, Animals, Cell Communication, Dendrites, Interneurons, Neural Inhibition, Neural Pathways, Organ Culture Techniques, Receptors, GABA-A, Synapses, Rats, Wistar, Pyramidal Cells, Patch-Clamp Techniques, Neocortex, Rats, Inhibitory Postsynaptic Potentials
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