Time-dependent reversal of long-term potentiation by brief cooling shocks in rat hippocampal slices

Using a recording chamber built with peltier elements, we studied the effects of fast and brief reductions in temperature on synaptic transmission and plasticity in area CA1 of rat hippocampal slices. Cooling shocks consisted of a drop in temperature from 33°C to 30°C, 27°C or 24°C for 2–5 min. Equilibrium to the new temperature was reached in about 30 s. During these cooling episodes, marked modifications of the size and time course of synaptic responses were observed. Changing the temperature for 4–5 min from 33°C to 24°C resulted in a 75% reduction in amplitude and 158% prolongation of the rise time of excitatory postsynaptic potentials (EPSPs). These changes were followed by a complete recovery of synaptic transmission. This recovery was very fast to the EPSP rise time (about 30 s), but much slower for the amplitude or initial slope (20–30 min). This slow recovery was correlated with changes in size of the presynaptic fiber volley, thereby indicating transient modifications of cell excitability. Application of cooling episodes of 4–5 min from 33°C to 24°C during the first 20 min that followed induction of long-term potentiation resulted in a complete reversal of synaptic potentiation. The LTP abolished by a cooling shock could be re-instated by re-applying high frequency trains. Several sequential induction/abolition effects could thus be obtained. In contrast, cooling episodes applied later than 25 min after LTP induction did not affect synaptic potentiation. These results show that fast and transient modifications in temperature can be used to explore mechanisms of synaptic transmission and plasticity, and they indicate that LTP can be fully reversed by cooling shocks applied during a specific time window after high frequency stimulation.