Long-Lasting Synaptic Potentiation Induced by Depolarization Under Conditions That Eliminate Detectable Ca Signals

Reyes FD, Walters ET. Long-lasting synaptic potentiation induced by depolarization under conditions that eliminate detectable Ca signals. J Neurophysiol 103: 1283–1294, 2010. First published December 30, 2009; doi:10.1152/jn.00704.2009. Activity-dependent alterations of synaptic transmission important for learning and memory are often induced by Ca signals generated by depolarization. While it is widely assumed that Ca is the essential transducer of depolarization into cellular plasticity, little effort has been made to test whether Ca -independent responses to depolarization might also induce memory-like alterations. It was recently discovered that peripheral axons of nociceptive sensory neurons in Aplysia display long-lasting hyperexcitability triggered by conditioning depolarization in the absence of Ca entry (using nominally Ca -free solutions containing EGTA, “0Ca/EGTA”) or the absence of detectable Ca transients (adding BAPTA-AM, “0Ca/EGTA/BAPTA-AM”). The current study reports that depolarization of central ganglia to 0 mV for 2 min in these same solutions induced hyperexcitability lasting 1 h in sensory neuron processes near their synapses onto motor neurons. Furthermore, conditioning depolarization in these solutions produced a 2.5-fold increase in excitatory postsynaptic potential (EPSP) amplitude 1–3 h afterward despite a drop in motor neuron input resistance. Depolarization in 0 Ca/EGTA produced long-term potentiation (LTP) of the EPSP lasting 1 days without changing postsynaptic input resistance. When re-exposed to extracellular Ca during synaptic tests, prior exposure to 0Ca/EGTA or to 0Ca/EGTA/BAPTA-AM decreased sensory neuron survival. However, differential effects on neuronal health are unlikely to explain the observed potentiation because conditioning depolarization in these solutions did not alter survival rates. These findings suggest that unrecognized Ca -independent signals can transduce depolarization into long-lasting synaptic potentiation, perhaps contributing to persistent synaptic alterations following large, sustained depolarizations that occur during learning, neural injury, or seizures.