Article

Interneurons of the neocortical inhibitory system

Laboratory of Neural Microcircuitry, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Nature reviews Neuroscience (Impact Factor: 31.38). 11/2004; 5(10):793-807. DOI: 10.1038/nrn1519
Source: PubMed

ABSTRACT Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.

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    • "Interneuron health is compromised in schizophrenia as evidenced by reduced gene expression and protein levels of glutamic acid decarboxylase (GAD67), an enzyme that synthesizes GABA, in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia (Akbarian et al., 1995; Woo et al., 1998; Guidotti et al., 2000; Lewis et al., 2004b; Thompson et al., 2009; Duncan et al., 2010). These cortical GABAergic inhibitory interneurons are a heterogeneous population of neurons that vary based on morphology, electrophysiological properties, laminar distribution, innervation of pyramidal neurons and expression of neuropeptides and calcium binding proteins (Markram et al., 2004; Petilla Interneuron Nomenclature GROUP, 2008). Three largely independent populations of interneurons expressing i) parvalbumin (PV), ii) somatostatin/calbindin (SST/CB) and iii) calretinin/vasoactive intestinal peptide (CR/VIP) have been identified (Somogyi et al., 1998). "
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    ABSTRACT: Late adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone. Testosterone removal by gonadectomy reduced gene expression of some BDNF transcripts in monkey and rat frontal cortices and the BDNF mRNA reduction was prevented by testosterone replacement. In rat, testosterone replacement increased the potential for classical TrkB signalling by increasing the full length to truncated TrkB mRNA ratio, whereas in the monkey cortex, circulating testosterone was negatively correlated with the TrkB full length/truncated mRNA ratio. We did not identify changes in interneuron gene expression in monkey frontal cortex in response to gonadectomy, and in rat, we showed that only somatostatin mRNA was decreased by gonadectomy but not restored by testosterone replacement. We identified complex and possibly species-specific, relationships between BDNF/TrkB gene expression and interneuron marker gene expression that appear to be dependent on the presence of testosterone at adolescence in rat and monkey frontal cortices. Taken together, our findings suggest there are dynamic relationships between BDNF/TrkB and interneuron markers that are dependent on the presence of testosterone but that this may not be a straightforward increase in testosterone leading to changes in BDNF/TrkB that contributes to interneuron health. Copyright © 2015. Published by Elsevier B.V.
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    • "The H101 GAD-67 antibody has been shown to detect a similar number of GABA cells as other anti- GABA antibodies (Akema et al., 2005). Parvalbumin is a calcium-binding protein that is found in basket and chandelier subtype GABAergic cells (Conde et al., 1994; Gabbott et al., 1997) that directly modulate efferent signaling of cortical pyramidal neurons (Miles et al., 1996; Markram et al., 2004; Lewis et al., 2005). Specificity of the PV 25 anti-parvalbumin antibody has been validated in immunohistochemistry studies of cortical and muscle tissue from wild-type versus parvalbumin knockout mice (Schwaller et al., 1999, 2004). "
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    ABSTRACT: Neural function within the medial prefrontal cortex (mPFC) regulates normal cognition, attention and impulse control, implicating neuroregulatory abnormalities within this region in mental dysfunction related to schizophrenia, depression and drug abuse. Both serotonin -2A (5-HT2A) and -2C (5-HT2C) receptors are known to be important in neuropsychiatric drug action and are distributed throughout the mPFC. However, their interactive role in serotonergic cortical regulation is poorly understood. While the main signal transduction mechanism for both receptors is stimulation of phosphoinositide production, they can have opposite effects downstream. 5-HT2A versus 5-HT2C receptor activation oppositely regulates behavior and can oppositely affect neurochemical release within the mPFC. These distinct receptor effects could be caused by their differential cellular distribution within the cortex and/or other areas. It is known that both receptors are located on GABAergic and pyramidal cells within the mPFC, but it is not clear whether they are expressed on the same or different cells. The present work employed immunofluorescence with confocal microscopy to examine this in layers V-VI of the prelimbic mPFC. The majority of GABA cells in the deep prelimbic mPFC expressed 5-HT2C receptor immunoreactivity. Furthermore, most cells expressing 5-HT2C receptor immunoreactivity notably co-expressed 5-HT2A receptors. However, 27% of 5-HT2C receptor immunoreactive cells were not GABAergic, indicating that a population of prelimbic pyramidal projection cells could express the 5-HT2C receptor. Indeed, some cells with 5-HT2C and 5-HT2A receptor co-labeling had a pyramidal shape and were expressed in the typical layered fashion of pyramidal cells. This indirectly demonstrates that 5-HT2C and 5-HT2A receptors may be commonly co-expressed on GABAergic cells within the deep layers of the prelimbic mPFC and perhaps co-localized on a small population of local pyramidal projection cells. Thus a complex interplay of cortical 5-HT2A and 5-HT2C receptor mechanisms exists, which if altered, could modulate efferent brain systems implicated in mental illness. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 03/2015; 297. DOI:10.1016/j.neuroscience.2015.03.050 · 3.33 Impact Factor
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    • "Throughout the CNS, inhibitory GABAergic neurons play a crucial role in controlling neuronal output. Inhibitory control usually relies on diverse neuronal types, which exhibit distinct morphological and physiological properties as well as specific intricate wiring patterns (Briggman et al., 2011; Markram et al., 2004). In the inner retina, laterally extending inhibitory amacrine cell networks made from diverse cell types (>35 types) control the vertical flow of visual information through the dozen or so types of excitatory bipolar cells that feed into output ganglion cells (MacNeil and Masland, 1998). "
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    ABSTRACT: Local and global forms of inhibition controlling directionally selective ganglion cells (DSGCs) in the mammalian retina are well documented. It is established that local inhibition arising from GABAergic starburst amacrine cells (SACs) strongly contributes to direction selectivity. Here, we demonstrate that increasing ambient illumination leads to the recruitment of GABAergic wide-field amacrine cells (WACs) endowing the DS circuit with an additional feature: size selectivity. Using a combination of electrophysiology, pharmacology, and light/electron microscopy, we show that WACs predominantly contact presynaptic bipolar cells, which drive direct excitation and feedforward inhibition (through SACs) to DSGCs, thus maintaining the appropriate balance of inhibition/excitation required for generating DS. This circuit arrangement permits high-fidelity direction coding over a range of ambient light levels, over which size selectivity is adjusted. Together, these results provide novel insights into the anatomical and functional arrangement of multiple inhibitory interneurons within a single computational module in the retina. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neuron 03/2015; DOI:10.1016/j.neuron.2015.02.035 · 15.98 Impact Factor
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