Interneuron cell types are fit to function

Kepecs, Adam; Fishell, Gordon

doi:10.1038/nature12983

Cited by 1,110Neuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanismsNeural dynamics and brain function

Interneuron cell types are fit to function

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Kepecs, Adam, Fishell, Gordon·2014·Nature

DOI 10.1038/nature12983PMC PMC4349583

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Abstract

Understanding brain circuits begins with an appreciation of their component parts - the cells. Although GABAergic interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define interneuron types by function.

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Interneuron subtypes differ in expression of molecules such as calcium-binding proteins and neuropeptides.
“IN subtypes differ in their expression of molecules such as calcium-binding proteins and neuropeptides”
From GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits (2016) · cites this paper as Kepecs and Fishell, 2014
Transcriptomic data from development appear consistent with the idea that early development is dominated by transcription-factor cascades and positive feedback, which later give way to activity-dependent feedback that refines neuronal form and synaptic connections.
“Developmental transcriptomic data seems compatible with the hypothesis that that cascades of transcription factors and positive feedback autoregulatory loops predominate early in development, but pass the baton to activity-dependent feedback mechanisms that fine-tune neuronal morphology and synaptic connectivity (see (Fishell and Heintz, 2013; Kepecs and Fishell, 2014) for review).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Kepecs and Fishell, 2014
Cortical interneurons are developmentally derived from progenitors in the medial, caudal and lateral ganglionic eminences.
“This diverse group of neurons is developmentally derived from progenitors residing in embryonic proliferative zones known as the medial, caudal and lateral ganglionic eminences (MGE, CGE, LGE, respectively)1.”
From Developmental diversification of cortical inhibitory interneurons (2018) · cites this paper as [1]
Decades of developmental studies established a clear division of transcription programmes between interneurons derived from the medial and caudal ganglionic eminence.
“For example, decades of developmental studies have established a clear division of transcription programmes between the interneurons derived from the medial and caudal ganglionic eminence (MGE and CGE, respectively)9,31,32,33.”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [9]
Defining neuronal types on the basis of function seems intuitive and most relevant to nervous system operation, but neuronal functions manifest at multiple levels that carry different meanings, vary according to behavioural context, and thus seem not well suited for defining cell types.
“Defining neuronal types on the basis of their ‘function’ seems intuitive and the most relevant to nervous system operation9,51, but neuronal functions manifest at multiple levels that carry different meanings, vary according to behavioural context, and thus seem not to be well suited for use in defining cell types.”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [9]

The cardinal identity of a cell is probably already instilled at the postmitotic stage during development, and its subsequent phenotypic differentiation and expression are regulated by extrinsic signals such as cell interactions and neural activity.
“The cardinal identity of a cell is probably already instilled at the postmitotic stage during development9,61,62,63,64, and its subsequent phenotypic differentiation and expression are regulated by extrinsic signals such as cell interactions and neural activity.”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [9]
PVBCs have origin in the MGE with specification driven by the homeodomain transcription factor Nkx2.1 (21% of MGE-derived interneurons).
“PVBCs have origin in the MGE with specification driven by the homeodomain transcription factor Nkx2.1 (21% of MGE-derived interneurons, see assumptions above) (147, 575, 1138, 1233).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [575]
Interneuron diversity does not emerge in response to activity-dependent mechanisms in the cortex, but is established early before cells reach the cortex by specific transcriptional programs that unfold over weeks.
“This suggests that interneuron diversity does not emerge in response to activity-dependent mechanisms in the cortex (1, 9), but rather is established early, before these cells reach the cortex, by specific transcriptional programs that then unfold over the course of several weeks.”
From Early emergence of cortical interneuron diversity in the mouse embryo (2018) · cites this paper as [1]
MGE produces SST and PVALB cortical types; CGE produces VIP and LAMP5 cortical types.
“(the MGE gives rise to SST and PVALB cortical types; the CGE gives rise to VIP and LAMPS cortical types)”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [19]
Vip and Tac2, the mouse homologue of TAC3, are neuropeptide genes linked to CGE origin in mouse.
“Vip and Tac2 (the mouse homologue of TAC3) are neuropeptide genes associated with a CGE origin in the mouse19”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [19]
In mouse, neocortical Lamp5+ interneurons mainly comprise neurogliaform and single-bouquet types, the most numerous layer-1 neurons with distinct morphological, neurochemical and connectivity properties.
“In the mouse, neocortical Lamp5+ interneurons primarily consist of neurogliaform and single-bouquet types, which are the most numerous layer-1 neurons and have distinct morphological, neurochemical and connectivity properties19.”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [19]
Many markers commonly used for mouse interneuron subtypes (Calb1, Calb2, Htr3a, Reln, Cck, Nos1) had different expression patterns across corresponding primate subtypes.
“many markers that are widely used to identify specific subtypes of interneurons in mice (such as Calb1, Calb2, Htr3a, Reln, Cck and Nos1)19,33 had different patterns of expression across the corresponding subtypes in primates”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [19]
Diverse sources of inhibition from the various interneuronal types are believed to enable networks to achieve more complex behaviors, including oscillations.
“Since the diverse sources of inhibition from the various interneuronal types are believed to enable networks to achieve more complex behaviors, including oscillations (Soltesz, 2006; Rotstein et al., 2005; Kepecs and Fishell, 2014)”
From Interneuronal mechanisms of hippocampal theta oscillations in a full-scale model of the rodent CA1 circuit (2016) · cites this paper as Kepecs and Fishell, 2014

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Authors: Kepecs, A., & Fishell, G.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2014-01
Volume: 505
Issue: 7483
Pages: 318-326
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12983
PMC: PMC4349583
OpenAlex: W1970789949
Cited by: 1,110
References: 120
Citations by year: 2026: 46 · 2025: 95 · 2024: 85 · 2023: 77 · 2022: 92 · 2021: 114 · 2020: 92 · 2019: 118 · 2018: 105 · 2017: 107 · 2016: 82 · 2015: 71 · 2014: 26
FWCI: 10.89
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institute of Mental Health (R01MH071679, MH095147, R01MH095147, MH071679, R37MH071679)
National Institute of Neurological Disorders and Stroke (NS 081297, P01NS074972, R01NS075531, NS074972, R01NS081297)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords: GABAergic interneurons, interneuron classification, brain circuits, inhibition, telencephalon, interneuron development
MeSH terms: Animals, Behavior, Humans, Interneurons, Mental Processes, Models, Neurological, Neural Pathways, Cell Lineage, Cell Proliferation

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