The process of reinnervation in the dentate gyrus of adult rats: gene expression by neurons during the period of lesion-induced growth

Abstract

Neurons in the hippocampal dentate gyrus are extensively reinnervated following the destruction of their normal inputs from the ipsilateral entorhinal cortex (EC). The present study evaluates gene expression by dentate granule neurons and the neurons giving rise to the sprouting connections during the period of synapse growth. Adult male rats were prepared for in situ hybridization at 2, 4, 6, 8, 10, 12, 14, 20, and 30 days following unilateral EC lesions. Sections were hybridized using 35S-labeled cRNA probes for mRNAs that encode proteins thought to be important for neuronal structure and/or synapse function, including (1) mRNAs that are normally present in dendrites--the mRNAs for the high molecular weight microtubule-associated protein 2 (MAP2) and the alpha-subunit of calcium/calmodulin-dependent protein kinase II (CAMII kinase), (2) mRNAs that are upregulated in neurons that are regenerating their axons (T alpha 1 tubulin and F1/GAP43) and (3) mRNAs for proteins that are the principal constituents of neurofilaments and microtubules (the low molecular weight neurofilament protein NF68 and beta-tubulin). Although there were small changes in the levels of labeling for the mRNAs that are normally present in dendrites, there were no dramatic increases in the levels of any of the mRNAs either in dentate granule cells or in neurons giving rise to the reinnervating fibers at any postlesion interval. These results indicate that neurons in mature animals can substantially remodel their synaptic terminals and their dendrites in the absence of large-scale changes in gene expression (at least as measured by steady-state mRNA levels at various time points).