ROBERTSON, R.M.; Queen’s University, Kingston: 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, such as those controlling locomotion and ventilation, 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 (flight, jump, and ventilation of locusts, neuromuscular transmission and larval peristaltic locomotion in drosophila, respiration in mice) we have been investigating the mechanisms underlying stress-mediated neuroprotection, particularly thermotolerance imparted by a prior heat shock. Neuronal potassium conductance, action potential generation and synaptic transmission 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. Heat shock also increases short-term plasticity at insect neuromuscular junctions and this can be mimicked by increased extracellular calcium concentrations, which is itself thermoprotective, indicating that presynaptic calcium handling may have a role. In the locust, prior anoxia imparts thermotolerance of action potential generation suggesting that different stressors activate common protective pathways. 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.