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      Interneurons in the mouse visual thalamus maintain a high degree of retinal convergence throughout postnatal development

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          Abstract

          Background

          The dorsal lateral geniculate nucleus (dLGN) of the mouse thalamus has emerged as a powerful experimental system for understanding the refinement of developing sensory connections. Interestingly, many of the basic tenets for such developmental remodeling (for example, pruning of connections to form precise sensory maps) fail to take into account a fundamental aspect of sensory organization, cell-type specific wiring. To date, studies have focused on thalamocortical relay neurons and little is known about the development of retinal connections onto the other principal cell type of dLGN, intrinsic interneurons. Here, we used a transgenic mouse line in which green fluorescent protein (GFP) is expressed within dLGN interneurons (GAD67-GFP), making it possible to visualize them in acutely prepared thalamic slices in order to examine their morphology and functional patterns of connectivity throughout postnatal life.

          Findings

          GFP-expressing interneurons were evenly distributed throughout dLGN and had highly complex and widespread dendritic processes that often crossed eye-specific borders. Estimates of retinal convergence derived from excitatory postsynaptic potential (EPSP) amplitude by stimulus intensity plots revealed that unlike relay cells, interneurons recorded throughout the first 5 weeks of life, maintain a large number (approximately eight to ten) of retinal inputs.

          Conclusions

          The lack of pruning onto interneurons suggests that the activity-dependent refinement of retinal connections in dLGN is cell-type specific. The high degree of retinal convergence onto interneurons may be necessary for these cells to provide both widespread and local forms of inhibition in dLGN.

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          Most cited references27

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          Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period.

          The neocortical GABAergic network consists of diverse interneuron cell types that display distinct physiological properties and target their innervations to subcellular compartments of principal neurons. Inhibition directed toward the soma and proximal dendrites is crucial in regulating the output of pyramidal neurons, but the development of perisomatic innervation is poorly understood because of the lack of specific synaptic markers. In the primary visual cortex, for example, it is unknown whether, and to what extent, the formation and maturation of perisomatic synapses are intrinsic to cortical circuits or are regulated by sensory experience. Using bacterial artificial chromosome transgenic mice that label a defined class of perisomatic synapses with green fluorescent protein, here we show that perisomatic innervation developed during a protracted postnatal period after eye opening. Maturation of perisomatic innervation was significantly retarded by visual deprivation during the third, but not the fifth, postnatal week, implicating an important role for sensory input. To examine the role of cortical intrinsic mechanisms, we developed a method to visualize perisomatic synapses from single basket interneurons in cortical organotypic cultures. Characteristic perisomatic synapses formed through a stereotyped process, involving the extension of distinct terminal branches and proliferation of perisomatic boutons. Neuronal spiking in organotypic cultures was necessary for the proliferation of boutons and the extension, but not the maintenance, of terminal branches. Together, our results suggest that although the formation of perisomatic synapses is intrinsic to the cortex, visual experience can influence the maturation and pattern of perisomatic innervation during a postnatal critical period by modulating the level of neural activity within cortical circuits.
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            Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway.

            Increases in the intracellular concentration of calcium ([Ca2+]i) activate various signaling pathways that lead to the expression of genes that are essential for dendritic development, neuronal survival, and synaptic plasticity. The mode of Ca2+ entry into a neuron plays a key role in determining which signaling pathways are activated and thus specifies the cellular response to Ca2+. Ca2+ influx through L-type voltage-activated channels (LTCs) is particularly effective at activating transcription factors such as CREB and MEF-2. We developed a functional knock-in technique to investigate the features of LTCs that specifically couple them to the signaling pathways that regulate gene expression. We found that an isoleucine-glutamine ("IQ") motif in the carboxyl terminus of the LTC that binds Ca2+-calmodulin (CaM) is critical for conveying the Ca2+ signal to the nucleus. Ca2+-CaM binding to the LTC was necessary for activation of the Ras/mitogen-activated protein kinase (MAPK) pathway, which conveys local Ca2+ signals from the mouth of the LTC to the nucleus. CaM functions as a local Ca2+ sensor at the mouth of the LTC that activates the MAPK pathway and leads to the stimulation of genes that are essential for neuronal survival and plasticity.
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              Developmental remodeling of the retinogeniculate synapse.

              Anatomical rearrangement of retinogeniculate connections contributes to the refinement of synaptic circuits in the developing visual system, but the underlying changes in synaptic function are unclear. Here, we study such changes in mouse brain slices. Each geniculate cell receives a surprisingly large number of retinal inputs (>20) well after eye-specific zones are formed. All but one to three of these inputs are eliminated over a 3-week period spanning eye opening. Remaining inputs are strengthened approximately 50-fold, in part through an increase in quantal size, but primarily through an increase in the number of release sites. Changes in release probability do not contribute significantly. Thus, a redistribution of release sites from many inputs to few inputs at this late developmental stage contributes to the precise receptive fields of thalamic relay neurons.
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                Author and article information

                Journal
                Neural Dev
                Neural Dev
                Neural Development
                BioMed Central
                1749-8104
                2013
                21 December 2013
                : 8
                : 24
                Affiliations
                [1 ]Department of Anatomical Sciences and Neurobiology, University of Louisville, 511 South Floyd Street, Louisville, KY 40202, USA
                [2 ]Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA
                Article
                1749-8104-8-24
                10.1186/1749-8104-8-24
                3878090
                24359973
                2436f24b-e89a-45c8-a180-096cf9971a64
                Copyright © 2013 Seabrook et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 September 2013
                : 6 December 2013
                Categories
                Short Report

                Neurosciences
                dorsal lateral geniculate nucleus,interneuron,retinogeniculate pathway,retinal convergence

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