Pharmacological Enhancement of Synaptic Efficacy,Spatial Learning,and Memory through Carbonic Anhyrase Activation in Rats

摘要

CA 1 pyramidal cells were recorded in rat hippocampal slices. In the presence of carbonic anhydrase activators, comicrostimu- lation of cholinergic inputs from stratum oriens and y-aminobu- tyric acid (GABA)ergic inputs from stratum pyramidale at low intensities switched the hyperpolarizing GABA-mediated inhib- itory postsynaptic potentials to depolarizing responses. In the absence of the activators, however, the same stimuli were insufficient to trigger the synaptic switch. This synaptic switch changed the function of the GABAergic synapses from excita- tion filter to amplifier and was prevented by carbonic anhydrase inhibitors, indicating a dependence on HCO;;. Intralateral ven- tricular administration of these same carbonic anhydrase acti- vators caused the rats to exhibit superior learning of the Morris water maze task, suggesting that the GABAergic synaptic switch is critical for gating the synaptic plasticity that underlies spatial memory formation. Increased carbonic anhydrase ac- tivity might, therefore, also enhance perception, processing, and storing of temporally associated relevant signals and rep- resents an important therapeutic target in learning and memory pharmacology.