Modulation of neural circuit operation by prior environmental stress

Many organisms are exposed to harsh environmental conditions that may impair the operation of vital neuronal circuits and imperil the animal before these conditions directly cause cell and tissue death. Prior exposure to extreme but sub-lethal stress has long-term effects on neural circuit function enabling motor pattern generators to operate under previously non-permissive conditions. Using several model systems we have been investigating the mechanisms underlying stress-mediated neuroprotection, particularly thermotolerance imparted by a prior heat shock. Prior anoxia and cold shock also impart thermotolerance of motor pattern generation suggesting that different stressors activate common protective pathways. Synaptic transmission, action potential generation and neuronal potassium conductance are modulated by prior heat shock. Pharmacological block of potassium channels, which increases the duration of action potentials and the amplitude of postsynaptic potentials, mimics the thermoprotective effect of a prior heat shock. A universal consequence of heat shock and other stresses is the increased expression of a suite of heat shock proteins of which HSP70 is most closely linked to organismal thermotolerance. Increased levels of HSP70 are sufficient, but not necessary for synaptic thermoprotection. Accumulating evidence suggests the existence of multiple, overlapping pathways for protection and that these mechanisms may be neuron specific depending on their functional roles.