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Science (New York, N.Y.) Apr 2014Many neurologic and psychiatric disorders are marked by imbalances between neural excitation and inhibition. In the cerebral cortex, inhibition is mediated largely by... (Review)
Review
Many neurologic and psychiatric disorders are marked by imbalances between neural excitation and inhibition. In the cerebral cortex, inhibition is mediated largely by GABAergic (γ-aminobutyric acid-secreting) interneurons, a cell type that originates in the embryonic ventral telencephalon and populates the cortex through long-distance tangential migration. Remarkably, when transplanted from embryos or in vitro culture preparations, immature interneurons disperse and integrate into host brain circuits, both in the cerebral cortex and in other regions of the central nervous system. These features make interneuron transplantation a powerful tool for the study of neurodevelopmental processes such as cell specification, cell death, and cortical plasticity. Moreover, interneuron transplantation provides a novel strategy for modifying neural circuits in rodent models of epilepsy, Parkinson's disease, mood disorders, and chronic pain.
Topics: Animals; Cell Count; Cell Separation; Cell- and Tissue-Based Therapy; Cerebral Cortex; Embryonic Development; Humans; Interneurons; Mental Disorders; Mice; Nervous System Diseases
PubMed: 24723614
DOI: 10.1126/science.1240622 -
Nature Jan 2014Understanding brain circuits begins with an appreciation of their component parts - the cells. Although GABAergic interneurons are a minority population within the... (Review)
Review
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.
Topics: Animals; Behavior; Cell Lineage; Cell Proliferation; Humans; Interneurons; Mental Processes; Models, Neurological; Neural Pathways
PubMed: 24429630
DOI: 10.1038/nature12983 -
Journal of Neurophysiology Sep 2022Integrative functions of spinal interneurons are well recognized but the relative role of different interneuronal populations in this process continues to be... (Review)
Review
Integrative functions of spinal interneurons are well recognized but the relative role of different interneuronal populations in this process continues to be investigated. It therefore appeared useful to review the principles of integration of afferent information by the interneurons analyzed so far as these principles should apply also to those remaining to be analyzed. Considering the results of both functional and morphological studies of spinal interneurons and of the morphology and immunochemistry of afferent fibers that provide input to them, the following five basic principles of processing of afferent information by them will be outlined; ) afferent information of any origin is forwarded to several neuronal populations, ) information from any sources of input is distributed unevenly, ) input from several sources is integrated by individual neurons as well as by their populations, ) specific combinations of input are integrated by different neuronal populations, and ) afferent input to spinal interneurons is only one of the features distinguishing their functional populations. As the spinal neuronal organization and properties of neurons and afferent fibers in the so far investigated species (cat, rodents, and primates) have been found to resemble, future studies using molecular techniques in the mouse should allow the new data to integrate with those of the preceding studies and the principles outlined earlier as well as any new ones should apply also in humans.
Topics: Afferent Pathways; Animals; Humans; Interneurons; Mice; Neurons, Afferent; Spinal Cord
PubMed: 36043802
DOI: 10.1152/jn.00344.2022 -
The Journal of Neuroscience : the... Sep 2018Changes in excitatory neuron and synapse structure have been recognized as a potential physical source of age-related cognitive decline. Despite the importance of...
Changes in excitatory neuron and synapse structure have been recognized as a potential physical source of age-related cognitive decline. Despite the importance of inhibition to brain plasticity, little is known regarding aging-associated changes to inhibitory neurons. Here we test for age-related cellular and circuit changes to inhibitory neurons of mouse visual cortex. We find no substantial difference in inhibitory neuron number, inhibitory neuronal subtypes, or synapse numbers within the cerebral cortex of aged mice compared with younger adults. However, when comparing cortical interneuron morphological parameters, we find differences in complexity, suggesting that arbors are simplified in aged mice. two-photon microscopy has previously shown that in contrast to pyramidal neurons, inhibitory interneurons retain a capacity for dendritic remodeling in the adult. We find that this capacity diminishes with age and is accompanied by a shift in dynamics from balanced branch additions and retractions to progressive prevalence of retractions, culminating in a dendritic arbor that is both simpler and more stable. Recording of visually evoked potentials shows that aging-related interneuron dendritic arbor simplification and reduced dynamics go hand in hand with loss of induced stimulus-selective response potentiation (SRP), a paradigm for adult visual cortical plasticity. Chronic treatment with the antidepressant fluoxetine reversed deficits in interneuron structural dynamics and restored SRP in aged animals. Our results support a structural basis for age-related impairments in sensory perception, and suggest that declines in inhibitory neuron structural plasticity during aging contribute to reduced functional plasticity. Structural alterations in neuronal morphology and synaptic connections have been proposed as a potential physical basis for age-related decline in cognitive function. Little is known regarding aging-associated changes to inhibitory neurons, despite the importance of inhibitory circuitry to adult cortical plasticity and the reorganization of cortical maps. Here we show that brain aging goes hand in hand with progressive structural simplification and reduced plasticity of inhibitory neurons, and a parallel decline in sensory map plasticity. Fluoxetine treatment can attenuate the concurrent age-related declines in interneuron structural and functional plasticity, suggesting it could provide an important therapeutic approach for mitigating sensory and cognitive deficits associated with aging.
Topics: Aging; Animals; Antidepressive Agents, Second-Generation; Dendrites; Evoked Potentials, Visual; Fluoxetine; Interneurons; Male; Mice, Transgenic; Neural Inhibition; Neuronal Plasticity; Optical Imaging; Visual Cortex
PubMed: 30108129
DOI: 10.1523/JNEUROSCI.0808-18.2018 -
Developmental Neurobiology Jan 2011The regulation of progenitor proliferation in developing brain in has been extensively studied in the cerebral cortex, but relatively little is known about progenitor... (Review)
Review
The regulation of progenitor proliferation in developing brain in has been extensively studied in the cerebral cortex, but relatively little is known about progenitor divisions in ventral germinal zones. Recent observations pertinent to interneuron genesis in the ventral forebrain, especially in the medial ganglionic eminence, indicate similarities to cerebral cortical neurogenesis and hint at some interesting differences between ventral and dorsal telencephalon progenitors. Proliferation within the ganglionic eminences is discussed from the vantage point of neural precursor cell cycles, especially G1-phase, and current models of neurogenic divisions in cortex that may apply to ventral forebrain as well.
Topics: Animals; Cell Cycle Proteins; Humans; Interneurons; Neural Stem Cells; Neurogenesis; Telencephalon
PubMed: 21154905
DOI: 10.1002/dneu.20823 -
Current Opinion in Neurobiology Jun 2014The exquisite architecture of cortex incorporates a myriad of inhibitory interneuron types. Until recently, the dearth of techniques for cell type identification in... (Review)
Review
The exquisite architecture of cortex incorporates a myriad of inhibitory interneuron types. Until recently, the dearth of techniques for cell type identification in awake animals has made it difficult to link interneuron activity with circuit function, computation and behavior. This situation has changed dramatically in recent years with the advent of novel tools for targeting genetically distinct interneuron types so their activity can be observed and manipulated. The association of different interneuron subtypes with specific circuit functions, such as gain modulation or disinhibition, is starting to reveal canonical circuit motifs conserved across neocortical regions. Moreover, it appears that some interneuron types are recruited at specific behavioral events and likely control the flow of information among and within brain areas at behavioral time scales. Based on these results we propose that interneuron function goes beyond network coordination and interneurons should be viewed as integral elements of cortical computations serving behavior.
Topics: Animals; Behavior; Brain Mapping; Cerebral Cortex; Interneurons; Models, Neurological; Nerve Net
PubMed: 24508565
DOI: 10.1016/j.conb.2014.01.007 -
Neurobiology of Disease May 2013GABAergic interneurons of the cerebral cortex (cINs) play crucial roles in many aspects of cortical function. The diverse types of cINs are classified into subgroups... (Review)
Review
GABAergic interneurons of the cerebral cortex (cINs) play crucial roles in many aspects of cortical function. The diverse types of cINs are classified into subgroups according to their morphology, intrinsic physiology, neurochemical markers and synaptic targeting. Recent advances in mouse genetics, imaging and electrophysiology techniques have greatly advanced our efforts to understand the role of normal cIN function and its dysfunction in neuropsychiatric disorders. In schizophrenia (SCZ), a wealth of data suggests that cIN function is perturbed, and that interneuron dysfunction may underlie key symptoms of the disease. In this review, we discuss the link between cINs and SCZ, focusing on the evidence for GABAergic signaling deficits from both SCZ patients and mouse models.
Topics: Animals; Cerebral Cortex; GABAergic Neurons; Humans; Interneurons; Neural Inhibition; Schizophrenia; gamma-Aminobutyric Acid
PubMed: 23201207
DOI: 10.1016/j.nbd.2012.11.013 -
Neuron Oct 2018The study of interneuron diversity in the spinal cord is complex and needs new models that can accelerate discovery. In this issue, Hoang et al. (2018) use ESC-derived...
The study of interneuron diversity in the spinal cord is complex and needs new models that can accelerate discovery. In this issue, Hoang et al. (2018) use ESC-derived neurons to create simplified microcircuits to study spinal interneuron diversification, connectivity, and function.
Topics: Interneurons; Spinal Cord; Stem Cells
PubMed: 30308170
DOI: 10.1016/j.neuron.2018.09.034 -
Cell Reports Jun 2022Dendrites are essential determinants of the input-output relationship of single neurons, but their role in network computations is not well understood. Here, we use a...
Dendrites are essential determinants of the input-output relationship of single neurons, but their role in network computations is not well understood. Here, we use a combination of dendritic patch-clamp recordings and in silico modeling to determine how dendrites of parvalbumin (PV)-expressing basket cells contribute to network oscillations in the gamma frequency band. Simultaneous soma-dendrite recordings from PV basket cells in the dentate gyrus reveal that the slope, or gain, of the dendritic input-output relationship is exceptionally low, thereby reducing the cell's sensitivity to changes in its input. By simulating gamma oscillations in detailed network models, we demonstrate that the low gain is key to increase spike synchrony in PV basket cell assemblies when cells are driven by spatially and temporally heterogeneous synaptic inputs. These results highlight the role of inhibitory neuron dendrites in synchronized network oscillations.
Topics: Action Potentials; Dendrites; Interneurons; Neurons; Parvalbumins
PubMed: 35705055
DOI: 10.1016/j.celrep.2022.110948 -
Neuron Nov 2005Neocortical interneurons are very diverse in morphological, physiological, molecular, and developmental characteristics. Recent work is discovering strong correlations... (Review)
Review
Neocortical interneurons are very diverse in morphological, physiological, molecular, and developmental characteristics. Recent work is discovering strong correlations between these phenotypic features, confirming the intuition of Cajal and Lorente that distinct classes of interneurons exist, each presumably mediating a different circuit function. A paper by Butt et al. in this issue of Neuron describes correlations between the developmental origin of interneurons and their anatomical, electrophysiological, and molecular properties. An effort to standardize the nomenclature of interneurons is underway. Because different interneuron subtypes have different ontogenic origin, they could be classified based on their developmental specification by transcription factors.
Topics: Animals; Cell Lineage; Electrophysiology; Interneurons; Neocortex
PubMed: 16301166
DOI: 10.1016/j.neuron.2005.11.012