GABAergic Interneurons: Implications for Understanding Schizophrenia and Bipolar Disorder

doi:10.1016/S0893-133X(01)00225-1

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GABAergic Interneurons: Implications for Understanding Schizophrenia and Bipolar Disorder

Journal Article•DOI•

GABAergic Interneurons: Implications for Understanding Schizophrenia and Bipolar Disorder

Francine M. Benes¹, Sabina Berretta², Sabina Berretta¹•Institutions (2)

McLean Hospital¹, Harvard University²

01 Jul 2001-Neuropsychopharmacology (Nature Publishing Group)-Vol. 25, Iss: 1, pp 1-27

TL;DR: Investigation of the GABA system in rodent, primate and human brain and the characterization of changes in specific phenotypic subclasses of interneurons in schizophrenia and bipolar disorder will undoubtedly provide important new insights into how the integration of this transmitter system may be altered in neuropsychiatric disease.

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About: This article is published in Neuropsychopharmacology.The article was published on 2001-07-01 and is currently open access. It has received 1063 citations till now. The article focuses on the topics: GABAergic & Interneuron.

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Journal Article•DOI•

Cortical inhibitory neurons and schizophrenia

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David A. Lewis¹, Takanori Hashimoto¹, David W. Volk¹•Institutions (1)

University of Pittsburgh¹

01 Apr 2005-Nature Reviews Neuroscience

TL;DR: Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia.

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Abstract: Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (γ-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

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2,153 citations

Journal Article•DOI•

The principal features and mechanisms of dopamine modulation in the prefrontal cortex

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Jeremy K. Seamans¹, Charles R. Yang•Institutions (1)

Medical University of South Carolina¹

01 Sep 2004-Progress in Neurobiology

TL;DR: Certain principles of DA mechanisms are identified by drawing on published, as well as unpublished data from PFC and other CNS sites to shed light on aspects of DA neuromodulation and address some of the existing controversies.

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1,515 citations

Cites background from "GABAergic Interneurons: Implication..."

...In rodent PFC, both D1- and D2-like receptors are found on pyramidal and non-pyramidal neurons (Vincent et al., 1993; Benes and Berretta, 2001)....
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Journal Article•DOI•

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

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Shikshya Shrestha, Steven M. Offer

24 Mar 2016

TL;DR: How various genetic and epigenetic events regulate the GABAergic genes in pre- and postnatal brain contribute to the pathogenesis of neurological disorders and can be used in the development of potential epigenetic therapy for these diseases.

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Abstract: The GABAergic neurotransmission is a highly conserved system that has been attributed to various regulatory events. There has been a notable number of studies on the importance of GABAergic neurotrans

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1,257 citations

Journal Article•DOI•

Interneuron dysfunction in psychiatric disorders

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Oscar Marín¹•Institutions (1)

Universidad Miguel Hernández de Elche¹

01 Feb 2012-Nature Reviews Neuroscience

TL;DR: In conclusion, animal models demonstrate that the molecular basis of disruption is linked to specific defects in the development and function of interneurons — the cells that are responsible for establishing inhibitory circuits in the brain.

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Abstract: The notion that the disruption of inhibitory circuits might underlie certain clinical features — notably cognitive impairment — in various neuropsychiatric disorders, including schizophrenia and autism, is receiving considerable attention. Focusing heavily on studies in animal models, Oscar Marin reviews the evidence indicating that the basis of such disruption is linked to specific defects in interneuron development and function.

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991 citations

Journal Article•DOI•

The origin and specification of cortical interneurons

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Carl P. Wonders¹, Stewart A. Anderson¹•Institutions (1)

Cornell University¹

01 Sep 2006-Nature Reviews Neuroscience

TL;DR: Recent data that are beginning to illuminate the origins and specification of distinct subgroups of cortical interneurons are discussed.

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Abstract: GABA-containing interneurons are crucial to both the development and function of the cerebral cortex. Unlike cortical projection neurons, which have a relatively conserved set of characteristics, interneurons include multiple phenotypes that vary on morphological, physiological and neurochemical axes. This diversity, and the relatively late, context-dependent maturation of defining features, has challenged efforts to uncover the transcriptional control of cortical interneuron development. Here, we discuss recent data that are beginning to illuminate the origins and specification of distinct subgroups of cortical interneurons.

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887 citations

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References

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Journal Article•DOI•

Interneurons of the hippocampus

[...]

Tamás F. Freund¹, György Buzsáki²•Institutions (2)

Hungarian Academy of Sciences¹, Rutgers University²

07 Dec 1998-Hippocampus

3,359 citations

"GABAergic Interneurons: Implication..." refers background in this paper

...These neurons show characteristics very similar to those described in the cerebral cortex; however, different subtypes of hippocampal basket neurons can be distinguished on the basis of axonal arborization, location, shape and neurochemical markers (Freund and Buzsaki 1996)....
[...]
...…of a pyramidal neuron, such as the soma, dendritic branches and spines, and the initial axonal segment, receives dense GABAergic synaptic innervation (O’Kusky and Colonnier 1982; Hendry et al. 1983; Houser et al. 1983; Beaulieu et al. 1992; for reviews see Jones 1993; Freund and Buzsaki 1996)....
[...]
...…implies that each contact may have only a very weak effect on the postsynaptic neuron, suggesting that the activity of dendritic inhibitory cells may have to be synchronized in order to effectively modulate the membrane potential of pyramidal neurons (Freund and Buzsaki 1996; Miles et al. 1996)....
[...]
...It is interesting to note that every segment of a pyramidal neuron, such as the soma, dendritic branches and spines, and the initial axonal segment, receives dense GABAergic synaptic innervation (O’Kusky and Colonnier 1982; Hendry et al. 1983; Houser et al. 1983; Beaulieu et al. 1992; for reviews see Jones 1993; Freund and Buzsaki 1996)....
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...However, when networks of interneurons are interconnected with one another, the final results of such complex interactions are not easily predictable by simple mathematical models (Freund and Buzsaki 1996)....
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Journal Article•DOI•

Cholinergic innervation of cortex by the basal forebrain : cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey

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M.-Marsel Mesulam¹, Elliott J. Mufson¹, Allan I. Levey², Bruce H. Wainer²•Institutions (2)

Beth Israel Deaconess Medical Center¹, University of Chicago²

20 Feb 1983-The Journal of Comparative Neurology

TL;DR: The organization of projections from the cholinergic neurons of the basal forebrain to neocortex and associated structures was investigated in the rhesus monkey with the help of horseradish peroxidase transport, acetyl‐cholinesterase histochemistry, and choline acetyltransferase immunohis‐tochemistry.

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Abstract: The organization of projections from the cholinergic neurons of the basal forebrain to neocortex and associated structures was investigated in the rhesus monkey with the help of horseradish peroxidase transport, acetyl-cholinesterase histochemistry, and choline acetyltransferase immunohis-tochemistry. Four groups of neurons contained cholinergic perikarya and were designated as Chl-Ch4. The Ch1 group corresponds to the medial septal nucleus; about 10% of its neurons are cholinergic, and it provides a substantial projection to the hippocampus. The Ch2 group corresponds to the vertical nucleus of the diagonal band; at least 70% of its neurons are cholinergic, and it is the major source of innervation that the hippocampus and hypothalamus receive from the Chl-Ch4 complex. The Ch3 group most closely corresponds to the horizontal nucleus of the diagonal band; only 1% of its neurons can definitely be shown to be cholinergic, and it is the major source of Chl-Ch4 projections to the olfactory bulb. The Ch4 group most closely corresponds to the nucleus basalis of Meynert; at least 90% of its neurons are cholinergic, and it has projections to widespread areas of cortex and to the amygdala. In fact, the Ch4 group provides the single major source of cholinergic innervation for the entire cortical surface. In this respect, it is analogous to the raphe nuclei and to the nucleus locus coeruleus, which constitute the major sources of widespread cortical serotonergic and nor-adrenergic innervation, respectively. The extensive Ch4 group can be divided into several subdivisions. Each subdivision has a preferential set of targets for its projections even though the connection patterns contain considerable overlap. The anteromedial subdivision of Ch4 is the major source of cholinergic projections to areas on the medial aspect of the cerebral hemispheres; the anterolateral Ch4 sub-division is the major source of cholinergic projections to frontoparietal op-ercular areas and to the amygdala; the intermediate Ch4 subdivision pro-vides the major cholinergic input for a variety of dorsal prefrontal, insular, posterior parietal, inferotemporal, and peristriate areas; and the posterior subdivision of Ch4 provides the major cholinergic innervation of superior temporal and immediately adjacent areas. The basal forebrain in the human contains a cytoarchitechture analogous to that of the monkey. The Ch4 group (nucleus basalis) of the human is very extensive and can be subdivided into the same components that were identfied in the monkey brain. Pathological changes in Ch4 neurons have been described in a variety of human disease. In Alzheimer's disease, the relatively selective depression of neocortical cholinergic innervation may be closely associated with the neuronal loss in Ch4, which has also been described inthis condition. In the rhesus monkey, all types of cortical areas receive substantial projections from the hippocampus. Virtually all of this hypothalamic input into neocortex arises from acetylcholinesterase-rich neurons which lack choline acetyltransferase. The hypothalamocortical pathway is therefore acetylcholinesterase-rich but not cholinergic.

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1,866 citations

"GABAergic Interneurons: Implication..." refers background in this paper

...Based on anatomic studies, a variety of subcortical nuclei such as the nucleus basalis of Meynert (Mesulam et al. 1983), raphe nuclei (Descarries et al. 1975; Lindvall and Bjorklund 1978), locus coeruleus (Levitt and Moore 1978), and ventral tegmental area (Thierry et al. 1973; Lindvall and Bjorklund 1984) send afferents to the cortex....
[...]
...Based on anatomic studies, a variety of subcortical nuclei such as the nucleus basalis of Meynert (Mesulam et al. 1983), raphe nuclei (Descarries et al....
[...]
...Based on anatomic studies, a variety of subcortical nuclei such as the nucleus basalis of Meynert (Mesulam et al. 1983), raphe nuclei (Descarries et al. 1975; Lindvall and Bjorklund 1978), locus coeruleus (Levitt and Moore 1978), and ventral tegmental area (Thierry et al. 1973; Lindvall and…...
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Journal Article•DOI•

Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation

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Miles A. Whittington¹, Roger D. Traub², Roger D. Traub³, John G. R. Jefferys¹•Institutions (3)

Imperial College London¹, IBM², Columbia University³

16 Feb 1995-Nature

TL;DR: It is proposed that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

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Abstract: Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

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1,625 citations

"GABAergic Interneurons: Implication..." refers background in this paper

...These networks have also been shown to be able to maintain rhythmic network activity even in the absence of excitatory inputs (Whittington et al. 1995)....
[...]
...…ranges (Buzsaki and Eidelberg 1983; Fraser and MacVicar 1991; Buzsaki et al. 1992; Soltesz and Deschenes 1993; Amzica and Steriade 1995; Bragin et al. 1995; Buzsaki and Chrobak 1995; Whittington et al. 1995; Ylinen et al. 1995a,b; Freund and Buzsaki, 1996; Jefferys et al. 1996; Buzsaki 1997)....
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...This results in coherent oscillations that have been proposed to ‘group’ or ‘ bind’ features detected in different cortical areas into a unified perceived object (Whittington et al. 1995)....
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Journal Article•DOI•

Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat

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Anatol Bragin¹, G. Jandó¹, Zoltan Nadasdy¹, J Hetke¹, K Wise¹, György Buzsáki¹ - Show less +2 more•Institutions (1)

Rutgers University¹

01 Jan 1995-The Journal of Neuroscience

TL;DR: It is suggested that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus and that Gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.

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Abstract: The cellular generation and spatial distribution of gamma frequency (40-100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40-100 Hz and 5-10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.

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1,529 citations

"GABAergic Interneurons: Implication..." refers background in this paper

...…frequency ranges (Buzsaki and Eidelberg 1983; Fraser and MacVicar 1991; Buzsaki et al. 1992; Soltesz and Deschenes 1993; Amzica and Steriade 1995; Bragin et al. 1995; Buzsaki and Chrobak 1995; Whittington et al. 1995; Ylinen et al. 1995a,b; Freund and Buzsaki, 1996; Jefferys et al. 1996;…...
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Journal Article•DOI•

Two networks of electrically coupled inhibitory neurons in neocortex

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Jay R. Gibson¹, Michael Beierlein¹, Barry W. Connors¹•Institutions (1)

Brown University¹

04 Nov 1999-Nature

TL;DR: Two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons are described, which may allow each inhibitory network to function independently.

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Abstract: Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex There are many types of inhibitory neurons, but their synaptic organization is poorly understood Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare The electrical synapses were strong enough to synchronize spikes in coupled interneurons Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently

...read moreread less

1,437 citations

"GABAergic Interneurons: Implication..." refers background in this paper

...‘Fast spiking’ neurons have been shown to be connected to each other both through chemical synapses as well as through electrical synapses (gap junctions) so that they have been proposed to form networks that might contribute to the synchronization of electrical activity in cortical neurons (Gibson et al. 1999)....
[...]
...1 Gene Dose Effects in Receptor Knockout Mice 5 ‘Low threshold’ neurons have been found to be selectively connected to each other through electrical synapses and thus proposed to play a role in generating synchronous inhibitory activity in the cortex (Gibson et al. 1999)....
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...1 throughout the cortex in which one specific interneuronal subtype preferentially synapses with neurons of the same type (Gibson et al. 1999)....
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...It has been shown that thalamic inputs selectively contact and strongly excite ‘fast spiking’ interneurons, while other interneuronal subtypes such as the ‘low threshold spiking’ neurons receive weaker or no thalamic input (Gibson et al. 1999)....
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...‘Fast spiking’ neurons have thus been proposed to be the mediators of fast, feedforward thalamocortical inhibition (Agmon and Connors 1992; Gibson et al. 1999)....
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