Intracellular correlates of spatial memory acquisition in hippocampal slices: Long-term disinhibition of CA1 pyramidal cells

Despite many advances in our understanding of synaptic models of memory suc h as long-term potentiation and depression, cellular mechanisms that correl ate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic respons es of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisitio n. Schaffer collateral stimulation evoked complex postsynaptic potentials ( PSP) consisting of the excitatory and inhibitory postsynaptic potentials (E PSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and c orrelation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyse s revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced I PSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related f acilitation as compared with the swim and naive controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no lea rning-specific synaptic changes. There were no WM training-specific modific ations of other intrinsic membrane properties. These data suggest that long -term disinhibition in a subset of CA1 PCs may facilitate cell discharges t hat represent and record the spatial location of a hidden platform in a Mor ris WM.