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 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-016-1345-3) contains supplementary material, which is available to authorized users.

Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition

“…Strikingly, both Tppp and GAD65 were upregulated at the mRNA level in vitro, and at the protein level in vivo, 2 weeks after discontinuation of lithium (PND 91), further confirming the positive modulatory effects of lithium on the neurogenic process as well as the importance of discontinuing the proliferative drive of lithium to allow integration of the newborn cells. The decrease in GAD65 expression after irradiation is in accordance with previous observations demonstrating that irradiation decreases the number and activation of GABAergic, parvalbuminpositive cells in the infralimbic cortex [71], while others reported increased GABA release in cannabinoid1 interneurons, decreased tonic GABAergic signaling, and increased principal cell activation in the hippocampus [72]. Both types of interneurons modulate principal cells activation and we previously demonstrated that early life irradiation increases excitability and impairs long-term potentiation in the adult dentate gyrus [73].…”

Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation

“…It is unknown how the HZE particle parameters used here influence dentate gyrus GABAergic interneurons and mossy cells in mature mice. However, exposure to other energetic particles that comprise space radiation alters the inhibitory network in the dentate gyrus and other hippocampal subregions of young adult rodents 86,87 . In the future, evaluation of GABAergic signaling and other measures relevant to sparse encoding (e.g.…”

Multi-domain cognitive assessment of male mice reveals whole body exposure to space radiation is not detrimental to high-level cognition and actually improves pattern separation

“…However, exposure to other energetic particles that comprise space radiation alters the inhibitory network in the dentate gyrus and other hippocampal subregions of young adult rodents (131,132) . In A third possibility -and related to conditions that favor sparse encoding -is that HZE particle exposure increases dentate gyrus neurogenesis.…”