Effects of Focal Ionizing Radiation of the Squid Stellate Ganglion on Synaptic and Axonal Transmission in the Giant-Fiber Pathway.

William F Gilly,Edward E Graves,Jackei Lo,Reese Zasio,P Teal,M Bret Schneider,John R Adler

doi:10.7759/cureus.13110

Abstract

Ionizing radiation is clinically used to treat neurological problems and reduce pathological levels of neural activity in the brain, but its cellular-level mechanisms are not well understood. Although spontaneous and stimulated synaptic activity has been produced in rodents by clinically and environmentally relevant doses of radiation, the effects on basic excitability properties of neurons have seldom been reported. This study examined the effects of focused ionizing radiation on synaptic transmission and action potential generation in the squid giant-fiber system, which includes the giant synapse between a secondary interneuron and the tertiary giant motor axons. Radiation of 140-300 Gy was delivered to a stellate ganglion of a living squid over several minutes, with the contralateral stellate ganglion serving as an internal control. No qualitative changes in the efficacy of synaptic transmission were noted in conjunction with stimulation of the input to the giant synapse, although in one irradiated ganglion, the refractory period increased from about 5 ms to more than 45 seconds. Small but significant changes in the action potential recorded from the giant motor axon in response to electrical stimulation were associated with an increased maximum rate of fall and a shortened action potential duration. Other action-potential parameters, including resting potential, overshoot, the maximum rate of the rise, and the refractory period were not significantly changed. Attempts to account for the observed changes in the action potential were carried through a Hodgkin-Huxley model of the action potential. This approach suggests that an increase in the maximum voltage-gated potassium conductance of about 50% mimics the action potential shortening and increased rate of fall that was experimentally observed. We propose that such an effect could result from phosphorylation of squid potassium channels.

Highlights

Sub-ablative doses of focused ionizing radiation delivered to brain circuit nodes have been proposed as a basis of therapy for some intractable conditions
This study examined the effects of focused ionizing radiation on synaptic transmission and action potential generation in the squid giant-fiber system, which includes the giant synapse between a secondary interneuron and the tertiary giant motor axons
No qualitative changes in the efficacy of synaptic transmission were noted in conjunction with stimulation of the input to the giant synapse, in one irradiated ganglion, the refractory period increased from about 5 ms to more than 45 seconds

Summary

Introduction

Sub-ablative doses of focused ionizing radiation delivered to brain circuit nodes have been proposed as a basis of therapy for some intractable conditions. Focused irradiation of 20 and 40 Gray (Gy) delivered to the hippocampal region in rats using a gamma knife substantially decreased penicillin-induced epileptiform spiking in hippocampal neurons several weeks after exposure, but not before [2]. Doses in this range delivered via a proton beam did not appear to alter synaptic input and excitability of granule cells in hippocampal slices, but stronger doses (90130 CGE) reduced activity and caused necrosis [3]. Older studies using similar doses of radiation to isolated hippocampal slices from guinea pigs reported a variety of effects related to the synaptic activity, which were observed immediately after irradiation [4,5]

Methods

Results

Discussion

Conclusion