22nd Annual NASA Space Radiation Investigators' Workshop (2011) 7093.pdf
Charged-Particle Radiation Affects Neuronal Properties of Mouse Hippocampal Slices
I,  Sokolova,  R.  Vlkolinsky,  *I.  Spigelman,  *V.  Marty,  M.  Campbell-­‐Beachler,  A .
Obenaus,  GA.
Nelson
Department  of  Radiation  Medicine,  Loma  Linda  University,  Loma  Linda,  CA  92354.
*  School  of  Dentistry;  UCLA,  Los  Angeles,  CA  90095-­‐1668.
Collective  effects  of  ionizing  radiation  on  astronauts’  CNS  during  deep  space   missions  are  largely  unknown.    It  has  been  demonstrated  in  mice  that  low  doses  of  high-­‐
LET  radiation  produce  persistent  cognitive  deficits.  Since  the  hippocampus  plays  a  major   role  in  cognition,  we  evaluated  long-­‐term  effects  of  low  doses  of  proton  radiation  on   electrophysiological  properties  of  the  CA1  pyramidal  neurons  and  granular  cells  of  the   dentate  gyrus  (DG)  in  the  mouse  hippocampus.  Adult  C57Bl6/J  mice  were  irradiated  with  a   proton  beam  at  a  1  Gy  dose  and,  3  months  after  irradiation,  electrophysiological  recordings   in  hippocampal  slices  from  both  irradiated  and  non-­‐irradiated  control  mice  were  obtained   using  the  patch-­‐clamp  technique.  In  the  CA1  pyramidal  neurons,  we  found  that  the  resting   membrane  potential,  threshold  for  the  Na +  current,  amplitude  of  after-­‐hyperpolarization,   and  the  action  potential  amplitudes  were  not  affected  by  irradiation.  However,  proton   radiation  reduced  the  amplitudes  of  spontaneous  excitatory  postsynaptic  currents  (EPSCs)
(7%,  p<0.01,  Kolmogoroff-­‐Smirnoff  test,  n=8-­‐15)  without  affecting  EPSC  frequency.  Proton   irradiation  also  affected  current-­‐voltage  relationships  in  the  CA1  pyramidal  neurons.
Membrane  currents  induced  by  depolarization  to  -­‐30  and  -­‐20  mV  and  reflecting  largely  the   persistent  Na +  and  K +  currents  were  significantly  lower  in  irradiated  mice  compared  to   those  in  the  control  mice  (p<0.03,  student  t-­‐test,  n=11).  In  the  DG  granular  cells,  proton   radiation  caused  a  dose-­‐dependent  decrease  in  the  amplitude  and  area  of  GABAergic   miniature  inhibitory  postsynaptic  currents  (mIPSCs)  indicating  decrements  in  inhibitory   synaptic  transmission.  No  other  kinetic  parameters  were  significantly  affected.  In   summary,  our  data  demonstrate  that  proton  irradiation  is  associated  with  persistent   changes  in  the  adult  mouse  hippocampus  leading  to  alteration  of  electrophysiological   properties  of  CA1  and  DG  neurons  with  possible  implications  to  impaired  cognitive   processes.