Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs
Open accessAbstract
Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating excitation with inhibition during the earliest steps of somatosensory processing in the cortex. Although the same TC afferents contact both FS and RS cells, FS cells receive larger and faster excitatory inputs from individual TC afferents. Here, we show that this larger thalamic excitation of FS cells occurs via GluR2-lacking AMPA receptors (AMPARs), and results from a fourfold larger quantal amplitude compared with the thalamic inputs onto RS cells. Thalamic afferents also activate NMDA receptors (NMDARs) at synapses onto both cells types, yet RS cell NMDAR currents are slower and pass more current at physiological membrane potentials. Because of these synaptic specializations, GluR2-lacking AMPARs selectively maintain feedforward inhibition of RS cells, whereas NMDARs contribute to the spiking of RS cells and hence to cortical recurrent excitation. Thus, thalamic afferent activity diverges into two routes that rely on unique complements of postsynaptic AMPARs and NMDARs to orchestrate the dynamic balance of excitation and inhibition as sensory input enters the cortex.
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These thalamocortical connections onto PV cells are provided by high quantal amplitude with calcium-permeable AMPA receptors and multiple clustered release sites.
“provided by high quantal amplitude with calcium permeable AMPA receptors (Hull et al., 2009) and multiple synaptic contacts forming clusters of neurotransmitter release sites (Bagnall et al., 2011).”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Hull et al., 2009
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- Authors
- Hull, C., Isaacson, J. S., & Scanziani, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Scanziani, M.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-07-15
- Volume
- 29
- Issue
- 28
- Pages
- 9127-9136
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2753516
- OpenAlex
- W2046924947
- Cited by
- 147
- References
- 56
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 11 · 2017: 16 · 2016: 10 · 2015: 10 · 2014: 13 · 2013: 14 · 2012: 12
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NH70058)
- National Institute of Mental Health (R01MH070058)
- National Institute of Neurological Disorders and Stroke (F32NS060585)
- 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
- thalamocortical afferents, postsynaptic mechanisms, fast-spiking interneurons, NMDA receptor, feedforward inhibition, excitation-inhibition balance, somatosensory processing, synaptic specializations
- MeSH terms
- Animals, Animals, Newborn, Biophysics, Calcium, Drug Interactions, Electric Stimulation, Mice, Inbred ICR, Neural Inhibition, Neural Pathways, Neurons, Pyridazines, Somatosensory Cortex, Strontium, Synapses, Thalamus, Time Factors, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, GABA Antagonists, Excitatory Postsynaptic Potentials, Principal Component Analysis, Mice, Inhibitory Postsynaptic Potentials, In Vitro Techniques
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