title: Neurophysiology of space travel: energetic solar particles cause cell type-specific plasticity of neurotransmission.
abstract: In the not too distant future, humankind will embark on one of its greatest adventures, the travel to distant planets. However, deep space travel is associated with an inevitable exposure to radiation fields. Space-relevant doses of protons elicit persistent disruptions in cognition and neuronal structure. However, whether space-relevant irradiation alters neurotransmission is unknown. Within the hippocampus, a brain region crucial for cognition, perisomatic inhibitory control of pyramidal cells (PCs) is supplied by two distinct cell types, the cannabinoid type 1 receptor (CB1)-expressing basket cells (CB1BCs) and parvalbumin (PV)-expressing interneurons (PVINs). Mice subjected to low-dose proton irradiation were analyzed using electrophysiological, biochemical and imaging techniques months after exposure. In irradiated mice, GABA release from CB1BCs onto PCs was dramatically increased. This effect was abolished by CB1blockade, indicating that irradiation decreased CB1-dependent tonic inhibition of GABA release. These alterations in GABA release were accompanied by decreased levels of the major CB1ligand 2-arachidonoylglycerol. In contrast, GABA release from PVINs was unchanged, and the excitatory connectivity from PCs to the interneurons also underwent cell type-specific alterations. These results demonstrate that energetic charged particles at space-relevant low doses elicit surprisingly selective long-term plasticity of synaptic microcircuits in the hippocampus. The magnitude and persistent nature of these alterations in synaptic function are consistent with the observed perturbations in cognitive performance after irradiation, while the high specificity of these changes indicates that it may be possible to develop targeted therapeutic interventions to decrease the risk of adverse events during interplanetary travel.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA. sanghunlee@uams.edu.|Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. sanghunlee@uams.edu.
authors.forename: Sang-Hun
authors.identifier: http://orcid.org/0000-0001-8880-2785
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083, Budapest, Hungary.|School of Ph.D. Studies, Semmelweis University, Budapest, Hungary.
authors.forename: Barna
authors.initials: B
authors.lastname: Dudok
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA, 92697, USA.
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA.
authors.forename: Kwang-Mook
authors.initials: KM
authors.lastname: Jung
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083, Budapest, Hungary.|School of Ph.D. Studies, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Zöldi
authors.affiliation: Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA.|Department of Neurosurgery, and Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, 94305, USA.
authors.forename: Mattia
authors.initials: M
authors.lastname: Maroso
authors.affiliation: Department of Neurosurgery, and Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, 94305, USA.
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Alexander
authors.affiliation: Division of Radiation Research, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, 92350, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.affiliation: Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Katona
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA, 92697, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
authors.affiliation: Department of Neurosurgery, and Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, 94305, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D010320:Parvalbumins / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid
keywords: Cannabinoid signaling system; GABAergic interneurons; Irradiation-induced cognitive impairments