The Effect of Caffeine on Various Forms of Synaptic Plasticity in the CA1 Region of Mouse Hippocampal Slices

Caffeine is a widely consumed psychostimulant known to affect memory, yet its dual role in impairing long-term potentiation (LTP) while enhancing cognitive performance remains unresolved. This study aimed to clarify this paradox by investigating the differential effects of caffeine on distinct forms of synaptic plasticity in the hippocampus. Using extracellular recordings in mouse hippocampal slices, we assessed long-term (LTP and E-S potentiation), short-term plasticity, and neuronal excitability under 30 μM caffeine exposure – a physiologically relevant concentration. Our findings confirm that caffeine suppresses LTP but does not inhibit E-S potentiation; instead, it enhances it. Furthermore, caffeine alters excitability in a form-dependent manner, reducing it following LTP and increasing it following E-S potentiation. We also show that caffeine blocks short-term synaptic plasticity regardless of prior LTP induction. These results suggest that E-S potentiation may serve as a caffeine-resistant mechanism for memory formation, potentially mediated by selective modulation of adenosine receptors. This study provides new insight into how caffeine influences synaptic processes underlying learning and memory.