The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors

By Soohyun Lee, Jens Hjerling-Leffler, Edward Zagha, G. Fishell, B. Rudy. Journal of Neuroscience, 2010

598 citations recorded by the source corpus.

A highly diverse population of neocortical GABAergic inhibitory interneurons has been implicated in multiple functions in information processing within cortical circuits. The diversity of cortical interneurons is determined during development and primarily depends on their embryonic origins either from the medial (MGE) or the caudal (CGE) ganglionic eminences. Although MGE-derived parvalbumin (PV)- or somatostatin (SST)-expressing interneurons are well characterized, less is known about the other types of cortical GABAergic interneurons, especially those of CGE lineage, because of the lack of specific neuronal markers for these interneuron subtypes. Using a bacterial artificial chromosome transgenic mouse line, we show that, in the somatosensory cortex of the mouse, the serotonin 5-hydroxytryptamine 3A (5-HT3A) receptor, the only ionotropic serotonergic receptor, is expressed in most, if not all, neocortical GABAergic interneurons that do not express PV or SST. Genetic fate mapping and neurochemical profile demonstrate that 5-HT3AR-expressing neurons include the entire spectrum of CGE-derived interneurons. We report that, in addition to serotonergic responsiveness via 5-HT3ARs, acetylcholine also depolarizes 5-HT3AR-expressing neurons via nicotinic receptors. 5-HT3AR-expressing neurons in thalamocortical (TC) recipient areas receive weak but direct monosynaptic inputs from the thalamus. TC input depolarizes a subset of TC-recipient 5-HT3AR neurons as strongly as fast-spiking cells, in part because of their high input resistance. Hence, fast modulation of serotonergic and cholinergic transmission may influence cortical activity through an enhancement of GABAergic synaptic transmission from 5-HT3AR-expressing neurons during sensory process depending on different behavioral states.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/96336df69ac6dc5f244cb31418d0460f6da0929d

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Citations in the corpus

Three Groups of Interneurons Account for Nearly 100% of Neocortical GABAergic Neurons (2011, methodology): “Qualitative observation of EGFP fluorescence in neocortical sections from the 5HT3aR-BAC mouse suggests that the population of 5HT3aR neurons is large and of comparable size to the PV and STT groups (Lee et al., 2010; Vucurovic et al., 2010).”
Three-dimensional intact-tissue sequencing of single-cell transcriptional states (2018, unknown): “Although the 5-HT(3A) receptor (Htr3a) expression has been reported in cortical inhibitory neurons (34), Htr3a has not been ranked as a critical genetic marker of inhibitory subtypes in V1.”
Inhibition of Inhibition in Visual Cortex: The Logic of Connections Between Molecularly Distinct Interneurons (2013, unknown): “Because of the reported large overlap between the expression of VIP and 5-HT3A receptor (Htr3a) we used the HTR3A-GFP line as a reference marker[25].”
Neuromodulation of brain states. (2012, unknown): “Much remains to be learned about how each neuromodulator affects circuit functions by activating its multiple receptors that are differentially expressed among neuronal subtypes (Bacci et al., 2005; Lee et al., 2010).”
A cortical circuit for gain control by behavioral state (2014, background): “One interesting feature of VIP neurons is that they express serotonin receptor 5HT3a receptor (Lee et al., 2010; Rudy et al., 2011).”
GABAergic interneurons in the neocortex: From cellular properties to circuits (2016, unknown): “In addition to IS, bursting and strongly adapting Vip cells have been reported (Cauli et al., 2000; Kawaguchi and Kubota, 1996; Lee et al., 2010; Porter et al., 1998; Prönneke et al., 2015).”
Principles of connectivity among morphologically defined cell types in adult neocortex (2015, unknown): “Connectivity patterns of three molecularly identified interneuronal types (PV + , SOM + , and VIP + ) in the developing neocortex have been recently revealed by optogenetic studies (28– 30).”
Critical periods in speech perception: new directions. (2015, background): “…neuromodulators (such as the serotonin and nicotinic acetylcholine receptor signaling onto particular GABA neurons) acutely regulates E-I balance (Lee et al. 2010), effectively disinhibiting the local circuitry to enable adult learning (Brown et al. 2012, Donato et al. 2013, Letzkus et al. 2011).”