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      Fabrication and modification of implantable optrode arrays for in vivo optogenetic applications

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          Recent advances in optogenetics have established a precisely timed and cell-specific methodology for understanding the functions of brain circuits and the mechanisms underlying neuropsychiatric disorders. However, the fabrication of optrodes, a key functional element in optogenetics, remains a great challenge. Here, we report reliable and efficient fabrication strategies for chronically implantable optrode arrays. To improve the performance of the fabricated optrode arrays, surfaces of the recording sites were modified using optimized electrochemical processes. We have also demonstrated the feasibility of using the fabricated optrode arrays to detect seizures in multiple brain regions and inhibit ictal propagation in vivo. Furthermore, the results of the histology study imply that the electrodeposition of composite conducting polymers notably alleviated the inflammatory response and improved neuronal survival at the implant/neural-tissue interface. In summary, we provide reliable and efficient strategies for the fabrication and modification of customized optrode arrays that can fulfill the requirements of in vivo optogenetic applications.

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          Neocortical excitation/inhibition balance in information processing and social dysfunction.

          Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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            Dopamine neurons modulate neural encoding and expression of depression-related behaviour.

            Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.
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              Midbrain circuits for defensive behaviour.

              Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.
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                Author and article information

                Contributors
                lp.wang@siat.ac.cn
                luyi@siat.ac.cn
                Journal
                Biophys Rep
                Biophys Rep
                Biophysics Reports
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2364-3439
                2364-3420
                20 April 2018
                20 April 2018
                2018
                : 4
                : 2
                : 82-93
                Affiliations
                [1 ]ISNI 0000000119573309, GRID grid.9227.e, Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, CAS Center for Excellence in Brain Science and Intelligence Technology, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, , Chinese Academy of Sciences, ; Shenzhen, 518055 China
                [2 ]Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen, 518055 China
                Article
                52
                10.1007/s41048-018-0052-4
                5937899
                29756008
                5ec7e3bd-2b1c-46c5-9c34-1d8bba8db724
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 3 March 2018
                : 20 March 2018
                Categories
                Method
                Custom metadata
                © The Author(s) 2018

                optogenetics,optrode,neural electrode,electrodeposition,optical stimulation,electrophysiological recording

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