Abstracts

Rationale: Early life seizures in normally developing rodents cause abnormalities in spatial cognition when the animals are adults. The cognitive impairments are associated with abnormalities in the function of place cells (hippocampal cells that fire in a location specific manner) which are an excellent surrogate marker of spatial cognition. Our ultimate goal is to develop therapeutic strategies that can be delivered to developing animals, whilst the brain still exhibits plasticity, in order to minimise the adverse effects of early life seizures. As a first step we investigated normal development of place cell function prior to evaluating disturbances of normal development associated with seizures. Methods: The experimental procedures were approved by the Animal Care and Use Committee of Dartmouth Medical School and were performed in accordance with NIH guidelines for the humane treatment of animals. Sprague-Dawley rats were implanted with custom built single unit electrodes in the dorsal hippocampus and pyramidal cells were recorded between P22 and P43. We initially investigated changes in coherence and probability of a pyramidal cell being a place cell as a function of age. In those cells that met criteria for place cells we then investigated changes in field size, cell firing rates and stability across recording sessions. Linear regression was used for all analyses. Results: 296 pyramidal cells were recorded in 19 animals. There was an increase in coherence (p = 0.005) and an increase in the probability that a recorded pyramidal cell was a place cell (p = 0.001) with increasing age. In the 168 place cells there was an increase in field size (p=0.048), peak firing rate (p=0.011) and centroid firing rate (p = 0.026) with increasing age. Place cells were also more likely to be stable as the animals became older (p = 0.001) Conclusions: The neural networks that subserve spatial cognition in the rodent undergo major developmental changes between P23 and P43. We suggest that diversions from these developmental trajectories could provide an early biomarker for cognitive status in adults. Careful characterisation of normal developmental trajectories now allows us to rigorously test strategies that could minimise the differences between trajectories in animals exposed to seizures and controls. This work was supported by NIH Grant NS044295 and NS056170.