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      Functional Properties of Dendritic Gap Junctions in Cerebellar Golgi Cells

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          Summary

          The strength and variability of electrical synaptic connections between GABAergic interneurons are key determinants of spike synchrony within neuronal networks. However, little is known about how electrical coupling strength is determined due to the inaccessibility of gap junctions on the dendritic tree. We investigated the properties of gap junctions in cerebellar interneurons by combining paired somato-somatic and somato-dendritic recordings, anatomical reconstructions, immunohistochemistry, electron microscopy, and modeling. By fitting detailed compartmental models of Golgi cells to their somato-dendritic voltage responses, we determined their passive electrical properties and the mean gap junction conductance (0.9 nS). Connexin36 immunofluorescence and freeze-fracture replica immunogold labeling revealed a large variability in gap junction size and that only 18% of the 340 channels are open in each plaque. Our results establish that the number of gap junctions per connection is the main determinant of both the strength and variability in electrical coupling between Golgi cells.

          Highlights

          • The mean conductance of dendritic gap junctions between Golgi cells is 0.9 nS

          • Dendritic gap junctions have 340 connexin36 channels of which 18% are open

          • Dendritic location contributes little to coupling strength variability

          • Gap junction number is the main determinant of coupling strength variability

          Abstract

          Variation in the strength of electrical synapses influences spike synchrony in interneuron networks. Szoboszlay et al. investigated the properties of electrical synapses between cerebellar Golgi cells and showed that the number of gap junctions is the main determinant of coupling strength variability.

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          Most cited references65

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          Two networks of electrically coupled inhibitory neurons in neocortex.

          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.
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            Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle.

            Tuft dendrites are the main target for feedback inputs innervating neocortical layer 5 pyramidal neurons, but their properties remain obscure. We report the existence of N-methyl-D-aspartate (NMDA) spikes in the fine distal tuft dendrites that otherwise did not support the initiation of calcium spikes. Both direct measurements and computer simulations showed that NMDA spikes are the dominant mechanism by which distal synaptic input leads to firing of the neuron and provide the substrate for complex parallel processing of top-down input arriving at the tuft. These data lead to a new unifying view of integration in pyramidal neurons in which all fine dendrites, basal and tuft, integrate inputs locally through the recruitment of NMDA receptor channels relative to the fixed apical calcium and axosomatic sodium integration points.
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              A network of fast-spiking cells in the neocortex connected by electrical synapses.

              Encoding of information in the cortex is thought to depend on synchronous firing of cortical neurons. Inhibitory neurons are known to be critical in the coordination of cortical activity, but how interaction among inhibitory cells promotes synchrony is not well understood. To address this issue directly, we have recorded simultaneously from pairs of fast-spiking (FS) cells, a type of gamma-aminobutyric acid (GABA)-containing neocortical interneuron. Here we report a high occurrence of electrical coupling among FS cells. Electrical synapses were not found among pyramidal neurons or between FS cells and other cortical cells. Some FS cells were interconnected by both electrical and GABAergic synapses. We show that communication through electrical synapses allows excitatory signalling among inhibitory cells and promotes their synchronous spiking. These results indicate that electrical synapses establish a network of fast-spiking cells in the neocortex which may play a key role in coordinating cortical activity.
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                Author and article information

                Contributors
                Journal
                Neuron
                Neuron
                Neuron
                Cell Press
                0896-6273
                1097-4199
                01 June 2016
                01 June 2016
                : 90
                : 5
                : 1043-1056
                Affiliations
                [1 ]Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest 1083, Hungary
                [2 ]János Szentágothai School of Neurosciences, Semmelweis University, Budapest 1085, Hungary
                [3 ]Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK
                Author notes
                []Corresponding author a.silver@ 123456ucl.ac.uk
                [∗∗ ]Corresponding author nusser@ 123456koki.hu
                [4]

                Co-first author

                [5]

                Present address: Institute of Basic Medical Sciences, University of Oslo, Oslo 0317, Norway

                Article
                S0896-6273(16)30020-4
                10.1016/j.neuron.2016.03.029
                4893164
                27133465
                92e79786-4b6c-430f-bab3-1f0ae7afade5
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 December 2015
                : 3 March 2016
                : 22 March 2016
                Categories
                Article

                Neurosciences
                gap junctions,electrical synapses,dendrites,interneuron,cerebellum,immunolocalization,connexin36

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