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Brain Struct Funct. 2017 Jul;222(5):2345-2357. doi: 10.1007/s00429-016-1345-3. Epub 2016 Nov 30.

Neurophysiology of space travel: energetic solar particles cause cell type-specific plasticity of neurotransmission.

Author information

1
Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA. sanghunlee@uams.edu.
2
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. sanghunlee@uams.edu.
3
Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083, Budapest, Hungary.
4
School of Ph.D. Studies, Semmelweis University, Budapest, Hungary.
5
Department of Radiation Oncology, University of California, Irvine, CA, 92697, USA.
6
Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA.
7
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
8
Department of Neurosurgery, and Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, 94305, USA.
9
Division of Radiation Research, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, 92350, USA.

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 CB1 blockade, indicating that irradiation decreased CB1-dependent tonic inhibition of GABA release. These alterations in GABA release were accompanied by decreased levels of the major CB1 ligand 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.

KEYWORDS:

Cannabinoid signaling system; GABAergic interneurons; Irradiation-induced cognitive impairments

PMID:
27905022
PMCID:
PMC5504243
DOI:
10.1007/s00429-016-1345-3
[Indexed for MEDLINE]
Free PMC Article

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