The hippocampal formation is a multicomponent region of the medial temporal lobe that has been implicated in declarative and relational memory processing. Our research program has investigated the connectivity and chemical neuroanatomy of the adult nonhuman primate hippocampal formation. Completion of our current studies, together with the work of other laboratories, has largely accomplished the goal of clarifying the basic functional organization of the adult primate hippocampal formation. With this application, we enter a new phase of research to investigate the postnatal structural development and functional maturation of the primate hippocampal formation. We begin this program of studies by addressing four specific aims. First, we will characterize the organization and maturity of the major input and output circuitry of the hippocampus at birth. We will do this by placing anterograde and retrograde neuroanatomical tracer injections in the entorhinai cortex of neonatal monkeys. Second, we will conduct stereological studies, measuring the volume of hippocampal regions, counting neuron numbers, measuring neuron sizes, and quantifying cell proliferation and neurogenesis, at different ages throughout postnatal development. This work will define the temporal pattern of postnatal development, and specify the age at which several morphological characteristics of the monkey hippocampal formation become adult-like. Third, we will use histochemical and immunohistochemical techniques to characterize the neurochemical development of the monkey hippocampal formation over the first year of life and compare this with the adult pattern. Finally, we will study the potential neuroanatomical reorganization that may subserve the partial recovery of declarative memory function observed in humans with early hippocampal damage. We will investigate this by placing neuroanatomical tracer injections in the entorhinai cortex and the CA3 hippocampal field of normal one-year old monkeys and one-year-old monkeys that received neonatal lesions of the CA1 field of the hippocampus. Taken together, these experiments will provide essential information on the postnatal maturation of the functional organization of the primate hippocampal formation. Our findings will have broad implications for the study of normal memory processes, including infantile amnesia, as well as human neurodevelopmental and genetic disorders, such as autism, schizophrenia and epilepsy.
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