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      New Concerns for Neurocognitive Function during Deep Space Exposures to Chronic, Low Dose-Rate, Neutron Radiation

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          Abstract

          As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates ∼1.5×10 5 higher than those actually encountered in space. Using a new, low dose-rate neutron irradiation facility, we have uncovered that realistic, low dose-rate exposures produce serious neurocognitive complications associated with impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and dose rate (1 mGy/d) exposures of mice to a mixed field of neutrons and photons result in diminished hippocampal neuronal excitability and disrupted hippocampal and cortical long-term potentiation. Furthermore, mice displayed severe impairments in learning and memory, and the emergence of distress behaviors. Behavioral analyses showed an alarming increase in risk associated with these realistic simulations, revealing for the first time, some unexpected potential problems associated with deep space travel on all levels of neurological function.

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          Most cited references58

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          Theta oscillations in the hippocampus.

          Theta oscillations represent the "on-line" state of the hippocampus. The extracellular currents underlying theta waves are generated mainly by the entorhinal input, CA3 (Schaffer) collaterals, and voltage-dependent Ca(2+) currents in pyramidal cell dendrites. The rhythm is believed to be critical for temporal coding/decoding of active neuronal ensembles and the modification of synaptic weights. Nevertheless, numerous critical issues regarding both the generation of theta oscillations and their functional significance remain challenges for future research.
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            Moving beyond P values: data analysis with estimation graphics

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              The medial temporal lobe.

              The medial temporal lobe includes a system of anatomically related structures that are essential for declarative memory (conscious memory for facts and events). The system consists of the hippocampal region (CA fields, dentate gyrus, and subicular complex) and the adjacent perirhinal, entorhinal, and parahippocampal cortices. Here, we review findings from humans, monkeys, and rodents that illuminate the function of these structures. Our analysis draws on studies of human memory impairment and animal models of memory impairment, as well as neurophysiological and neuroimaging data, to show that this system (a) is principally concerned with memory, (b) operates with neocortex to establish and maintain long-term memory, and (c) ultimately, through a process of consolidation, becomes independent of long-term memory, though questions remain about the role of perirhinal and parahippocampal cortices in this process and about spatial memory in rodents. Data from neurophysiology, neuroimaging, and neuroanatomy point to a division of labor within the medial temporal lobe. However, the available data do not support simple dichotomies between the functions of the hippocampus and the adjacent medial temporal cortex, such as associative versus nonassociative memory, episodic versus semantic memory, and recollection versus familiarity.
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                Author and article information

                Journal
                eNeuro
                eNeuro
                eneuro
                eneuro
                eNeuro
                eNeuro
                Society for Neuroscience
                2373-2822
                25 July 2019
                22 August 2019
                Jul-Aug 2019
                : 6
                : 4
                : ENEURO.0094-19.2019
                Affiliations
                [1 ]Department of Radiation Oncology, University of California , Irvine, California 92697
                [2 ]Department of Neurosurgery, Stanford University , California 94305
                [3 ]Department of Neurobiology and Behavior, University of California , Irvine, California 92697
                [4 ]Department of Environmental and Radiological Health Sciences, Colorado State University , Fort Collins, Colorado 80523
                [5 ]Department of Radiation Oncology, Eastern Virginia Medical School , Norfolk, Virginia 23507
                Author notes

                The authors declare no competing financial interests.

                Author contributions: M.M.A., J.E.B., I.S., and C.L.L. designed research; M.M.A., J.E.B., P.M.K., A.A.D.B., L.A.A., E.A.K., L.A., C.G., M.C.A., R.S.B., and C.M.F. performed research; M.M.A., J.E.B., P.M.K., T.B.B., and C.L.L. contributed unpublished reagents/analytic tools; M.M.A., J.E.B., P.M.K., E.A.K., R.A.B., and I.S. analyzed data; M.M.A., J.E.B., P.M.K., C.E.L.S., M.A.W., R.A.B., I.S., and C.L.L. wrote the paper.

                This work was supported by UCI Institute for Clinical and Translational Sciences (ICTS) KL2 training award KL2TR001416 (M.M.A.), NASA Specialized Center of Research (NSCOR) grant NNX15AK13G for funding the neutron irradiator, and NSCOR grant NNX15AI22G (R.A.B., I.S., C.L.L.).

                [*]

                M.M.A., J.E.B., and P.M.K. contributed equally to this work.

                Correspondence should be addressed to Charles L. Limoli at Climoli@ 123456uci.edu .
                Author information
                https://orcid.org/0000-0003-1493-3744
                https://orcid.org/0000-0002-1321-4142
                Article
                eN-NWR-0094-19
                10.1523/ENEURO.0094-19.2019
                6709229
                31383727
                b345661a-521f-4876-8d1e-058435ef279f
                Copyright © 2019 Acharya et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 13 March 2019
                : 8 July 2019
                : 16 July 2019
                Page count
                Figures: 5, Tables: 3, Equations: 6, References: 67, Pages: 15, Words: 11714
                Funding
                Funded by: http://doi.org/10.13039/100006203NASA | Johnson Space Center (JSC)
                Award ID: NNX15AI22G
                Categories
                3
                3.1
                New Research
                Disorders of the Nervous System
                Custom metadata
                July/August 2019

                cognitive dysfunction,electrophysiology,long-term potentiation,low dose-rate,neutrons,space radiation

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