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      Synaptically Induced Long-Term Modulation of Electrical Coupling in the Inferior Olive

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        1 , 2 , 1 , 2 , 1 ,
      Neuron
      Cell Press

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          Summary

          Electrical coupling mediated by gap junctions is widespread in the mammalian CNS, and the interplay between chemical and electrical synapses on the millisecond timescale is crucial for determining patterns of synchrony in many neural circuits. Here we show that activation of glutamatergic synapses drives long-term depression of electrical coupling between neurons of the inferior olive. We demonstrate that this plasticity is not triggered by postsynaptic spiking alone and that it requires calcium entry following synaptic NMDA receptor activation. These results reveal that glutamatergic synapses can instruct plasticity at electrical synapses, providing a means for excitatory inputs to homeostatically regulate the long-term dynamics of microzones in olivocerebellar circuits.

          Highlights

          • Chemical synapses trigger long-term depression of inferior olive electrical coupling

          • Depression of electrical coupling requires NMDAR activation and calcium entry

          • Plasticity is not triggered by postsynaptic spiking alone and EPSPs remain unchanged

          • Excitatory inputs can thus homeostatically regulate synchrony patterns in the olive

          Abstract

          The interplay between electrical and chemical synapses is crucial for determining patterns of synchrony in neuronal networks. Recording in the inferior olive, Mathy et al. show that coincident excitatory synaptic input and spiking can cause a sustained suppression of electrical coupling.

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          Most cited references55

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          The molecular basis of CaMKII function in synaptic and behavioural memory.

          Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the primary model by which to study the cellular and molecular basis of memory. Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP induction, is persistently activated by stimuli that elicit LTP, and can, by itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII autophosphorylation and dephosphorylation indicates that this kinase could serve as a molecular switch that is capable of long-term memory storage. Consistent with such a role, mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory. These results make CaMKII a leading candidate in the search for the molecular basis of memory.
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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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              Electrical coupling and neuronal synchronization in the Mammalian brain.

              Certain neurons in the mammalian brain have long been known to be joined by gap junctions, which are the most common type of electrical synapse. More recently, cloning of neuron-specific connexins, increased capability of visualizing cells within brain tissue, labeling of cell types by transgenic methods, and generation of connexin knockouts have spurred a rapid increase in our knowledge of the role of gap junctions in neural activity. This article reviews the many subtleties of transmission mediated by gap junctions and the mechanisms whereby these junctions contribute to synchronous firing.
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                Author and article information

                Contributors
                Journal
                Neuron
                Neuron
                Neuron
                Cell Press
                0896-6273
                1097-4199
                19 March 2014
                19 March 2014
                : 81
                : 6
                : 1290-1296
                Affiliations
                [1 ]Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
                Author notes
                []Corresponding author m.hausser@ 123456ucl.ac.uk
                [2]

                These authors contributed equally to this work

                Article
                S0896-6273(14)00009-9
                10.1016/j.neuron.2014.01.005
                3988996
                24656251
                535d32d8-d4c0-4eb0-a494-7aa89e3d7492
                © 2014 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

                History
                : 10 December 2013
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                Neurosciences
                Neurosciences

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