Developmental Changes in Excitatory Synapses in Hippocampus

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DESCRIPTION (provided by applicant): The entorhinal cortex and hippocampus are both critical for learning and memory. The entorhinal cortex has been implicated in several neurological diseases, including developmental disorders that cause mental retardation. One major input pathway from entorhinal cortex to hippocampus is the temporoammonic (TA) pathway to the CA1 region of hippocampus. The TA pathway provides specific sensory information to CA1, and it has been shown to be involved in memory consolidation. Because of the importance of the TA pathway to learning and memory, alterations in the functional properties of TA synapses could contribute to cognitive impairment in developmental disorders. Such changes might not be apparent at the morphological level, but would require electrophysiology to be detected. The investigators' long term objective is to use electrophysiology to look for changes in the function of synapses and circuits in animal models of developmental disorders. To lay the foundation for that research they will first investigating the changes in synaptic function that occur during normal development. They have previously shown changes during early postnatal development in presynaptic function of synapses in the other major input pathway to CA1, the Schaffer collateral (SC) pathway. In order to understand the impact of these developmental changes for hippocampal function, the investigators also need to know the properties of TA synapses and how they are modulated during development. Relatively little is known about the presynaptic function of TA synapses and how they compare to SC synapses, and nothing is known about whether the properties of TA synapses are also developmentally regulated. Because both TA and SC synapses influence the firing of CA1 neurons, the main output neurons of hippocampus, their dynamic properties are crucial determinants of normal hippocampal function and development of hippocampal circuitry. In this small grant application, the investigators will use hippocampal brain slices from rats as a model system, and use electrophysiology to measure the presynaptic properties of TA synapses in slices from juveniles versus young adults. They will test the hypothesis that developmental modulation of presynaptic properties is fundamentally different between TA synapses and SC synapses, and that short-term plasticity is different between TA synapses and SC synapses in both juveniles and young adults. Understanding the developmental changes in the different input pathways that influence CA1 cell firing will be important for understanding how the function of the hippocampal circuit changes during normal neonatal development. Together, this research provides the foundation for future studies on the functional properties and developmental modulation of hippocampal synapses and circuits that could contribute to cognitive impairment in animal models of developmental disorders that cause mental retardation.