Growth of a new fiber projection in the brain of adult rats: Re-innervation of the dentate gyrus by the contralateral entorhinal cortex following ipsilateral entorhinal lesions

Summary Ablation of the entorhinal cortex of the rat removes the major synaptic input to the granule cells of the ipsilateral dentate gyrus. Following unilateral entorhinal lesions in adult rats, we have examined the efferent projections of the remaining contralateral entorhinal cortex to determine if these might sprout to re-innervate the deafferented dentate gyrus. Autoradiographical tracing of the fiber projections of the remaining contralateral entorhinal cortex 60 days following lesions indicates that new fibers sprout and grow for several hundred microns into the denervated regions, to terminate on portions of the granule cell dendrites which would normally receive ipsilateral entorhinal afferents.These re-innervating fibers form electrophysiologically functional synaptic connections with the denervated dentate granule cells. In the normal animal, unilateral stimulation of the entorhinal cortex does not result in short latency activation of the contralateral dentate gyrus whereas following ipsilateral entorhinal lesions, re-innervation by contralateral entorhinal afferents is reflected electrophysiologically by the appearance of a new short latency evoked potential to contralateral entorhinal stimulation. By field potential analysis, we demonstrate that this new short latency evoked potential is a reflection of mono-synaptic activation of the denervated dentate granule cells by the re-innervating contralateral entorhinal fibers.In addition, the time course of contralateral entorhinal re-innervation is determined electrophysiologically. The new short latency response to contralateral entorhinal stimulation appears as early as 9 days post-lesion, matures functionally between 9 and 15 days, and after 15 days, remains apparently undiminished for as long as 200 days. This implies that the new synapses formed in response to a deafferenting lesion are formed rapidly and remain permanently capable of activating the dentate granule cells which had been deprived of ipsilateral entorhinal input.The material in this paper was included in a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the University of California at Irvine, Irvine, California 92664.