Temperature-dependent separation of a delayed-onset long-lasting enhancement mediated by coactivation of NMDA and metabotropic glutamate receptors following a transient exposure of extracellular high Ca²⁺

Transient increases in the concentration of extracellular Ca²⁺ play an essential role in various physiological and/or pathological implications. Here the effect of low temperatures on synaptic transmission modulated by a brief increase in extracellular high Ca²⁺ was studied in CA1 area of hippocampal slices from hamsters. A high Ca²⁺ pulse (4.5 mM) induced a long-lasting enhancement at 25, 20, or 17°C, but not at 15°C. While the temperature was lowered to 17°C, the overall expression of synaptic responses following a high Ca²⁺ pulse was separated into two sequential enhanced components: an initial component (approximately 30-40 min in duration), followed by a delayed-onset component that was sustained throughout the remainder of the experiment. Application of 100 μM D-2-amino-5-phosphonovalerate, a selective antagonist of N-methyl-D-asparate receptors, or (RS)-α-Methyl-4-carboxyphenylglycine, a selective antagonist of metabotropic glutamate (mGlu) receptors, during a high Ca²⁺ pulse at 17°C blocked the development of the delayed-onset enhanced component without affecting the initial enhanced component significantly. In contrast, the application of D-2-amino-5-phosphonovalerate or (RS)-α-Methyl-4-carboxyphenylglycine immediately after a high Ca²⁺ pulse at 17°C had no discernible effects on the development of both components. These results indicate that low temperatures (e.g. 17°C) unmasked two enhanced components that cannot be seen as separate components in the overall potentiation, while long-lasting enhancement was generated at higher temperatures (e.g. 25°C). The development of the delayed-onset enhanced component primarily depended on coactivation of N-methyl-D-asparate and mGlu receptors during a high Ca²⁺ challenge at 17°C. The findings here may provide new understanding of the use of low temperatures and promise significant insight into a novel therapeutic intervention in the CNS while the glutamatergic signaling pathway is abnormally activated by certain ambient insults, such as transient increases in the concentration of extracellular Ca²⁺.