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

Sang-Hun Lee,Kwang-Mook Jung,István Katona,Charles L Limoli,Miklós Zöldi,Barna Dudok,Allyson L Alexander,Vipan K Parihar,Young-Jin Kang,Ivan Soltesz,Mattia Maroso,Gregory A Nelson,Daniele Piomelli

doi:10.1007/s00429-016-1345-3

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.

Highlights

Deep space travel poses variety of challenges to humankind, including an unavoidable exposure to unique radiation fields that present a range of health risks (Cucinotta et al 2014)
Because recent studies have shown that high- and lowdose irradiation paradigms can compromise dendritic structures (Parihar and Limoli 2013; Allen et al 2015) and intrinsic properties (Sokolova et al 2015) of hippocampal principal neurons, we carried out a detailed analysis of the neuronal morphology and intrinsic properties of CB1BCs from control and proton-irradiated animals
Proton irradiation did not change passive or active electrophysiological properties of CB1BCs (Fig S2). These experiments showed that the morphological and intrinsic properties of CB1BCs remained unaltered by low-dose proton irradiation, in contrast to what has been shown in excitatory hippocampal cells (Parihar et al 2014; Sokolova et al 2015)

Summary

Introduction

Deep space travel poses variety of challenges to humankind, including an unavoidable exposure to unique radiation fields that present a range of health risks (Cucinotta et al 2014). Cognitive changes can be linked to structural alterations in specific neuronal subsets, involving reduced dendritic complexity and spine density and alterations in the distribution and levels of critical synaptic proteins (Lonart et al 2012; Parihar and Limoli 2013; Sweet et al 2014; Allen et al 2015; Chmielewski et al 2016). Despite these findings, relatively little is known regarding the impact of charged particles on specific excitatory and inhibitory circuits in the brain

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