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Activity-dependent attenuations in extracellular spike amplitude have been shown to correlate with a decrease in the effectiveness with which somatic action potentials back-propagate into the dendritic arbor of hippocampal pyramidal cells. In this paper we demonstrate that activity-dependent attenuations in amplitude occur during behavior and that the amount of attenuation is reduced with an animal's experience in an environment. The observed reductions are caused by an animal's experience within a specific environmental context, are dependent on functional NMDA receptors, and are accompanied by an increase in the effective coupling of pyramidal cells and interneurons. These results provide an important step in linking together in vivo studies with in vitro data and suggest that mechanisms of plasticity engaged during behavior may be sufficient to alter the biophysical and integrative properties of hippocampal pyramidal cells.

To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of pairs of neurons tuned to similar spatial locations. Pairs have uncorrelated firing even if their fields overlap. These results demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the proper representation of space in the CA1 region of the hippocampus.

Using experimental facts about long-term potentiation (LTP) and hippocampal place cells, we model how a spatial map of the environment can be created in the rat hippocampus. Sequential firing of place cells during exploration induces, in the model, a pattern of LTP between place cells that shifts the location coded by their ensemble activity away from the actual location of the animal. These shifts provide a navigational map that, in a simulation of the Morris maze, can guide the animal toward its goal. The model demonstrates how behaviorally generated modifications of synaptic strengths can be read out to affect subsequent behavior. Our results also suggest a way that navigational maps can be constructed from experimental recordings of hippocampal place cells.

Fura-2 and imaging technology were used to detect intracellular Ca2+ changes in CA1 pyramidal cells in hippocampal slices. During focal synaptic stimulation, one or more highly localized regions of Ca2+ elevation (hot spots) were detected in the dendrites. Ca2+ spread from the center of hot spots with properties consistent with diffusion. Several lines of evidence indicate that these hot spots were due to Ca2+ entry through N-methyl-D-aspartate synaptic channels. The spatial and temporal resolution of the method was sufficient to detect the response of single hot spots to single stimuli, thus providing a real-time method for monitoring local synaptic activity. Using this method, we show that synapses on the same dendrite differ in their probability of response and in their facilitation properties.