Neuronal sprouting has recently been proposed as a mechanism underlying the behavioral manifestation of schizophrenia. However, little is presently known about the behavioral significance of sprouting in the central nervous system (CNS). The purpose of this research is to evaluate the functional significance of Sprouting in the dentate gyrus (DG) of the hippocampal formation after unilateral lesions of the entorhinal cortex (EC) in rats. This study will focus on the contribution that a proliferated input (i.e., the crossed temporodentate projection -- CTD) makes to the recovery from spatial alternation deficits associated with unilateral EC damage. Two criteria will be used to assess whether the sprouting is behaviorally meaningful: 1) The time course of the reinnervation must parallel the time course of the behavioral recovery. 2) Systematic manipulation of the sprouted fibers must produce a concomitant change in behavior. This investigation will employ two experiments to attain the stated objective: A) Progressive lesions of the EC, which are known to accelerate septodentate and commissural/associational sprouting to DG, will be used to determine whether the rate of behavioral recovery is also accelerated. Spatial alternation will be used as the behavioral assay because previous evidence has shown it to be sensitive to the reinnervation of the DG after EC damage. B) An anatomical analysis relying on autoradiographic techniques will be performed to confirm that CTD sprouting is accelerated by progressive lesions. This project will lay the foundation for future work assessing the functional significance of CNS Sprouting.
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| Ramirez, J J; McQuilkin, M; Carrigan, T et al. (1996) Progressive entorhinal cortex lesions accelerate hippocampal sprouting and spare spatial memory in rats. Proc Natl Acad Sci U S A 93:15512-7 |
| Meeker, R; LeGrand, G; Ramirez, J et al. (1995) Antisense vasopressin oligonucleotides: uptake, turnover, distribution, toxicity and behavioral effects. J Neuroendocrinol 7:419-28 |
