INDUCTION OF NONCATALYTIC TRKB NEUROTROPHIN RECEPTORS DURING AXONAL SPROUTING IN THE ADULT HIPPOCAMPUS

Brain-derived neurotrophic factor (BDNF) and its signal transducing re ceptor, the TrkB tyrosine protein kinase, are expressed at high levels in the hippocampus of the adult brain, suggesting a role for BDNF mec hanisms in neuronal plasticity. To test this hypothesis, we used defin ed lesions of perforant path and fimbria-fornix, two major hippocampal afferents, to remove synapses on dendrites of dentate gyrus granule c ells and pyramidal cells of Ammon's horn and induce synaptic rearrange ments. These combined lesions remove afferent connections from entorhi nal cortex and septum and produce massive sprouting of axons of the co mmissural/associational pathways into the molecular layer of the hippo campal dentate gyrus. At days 1, 3, and 6, the lesions decreased BDNF mRNA expression ipsilaterally to approximately 50% of control, with co mplete recovery at 14 d. The lesions did not alter trkB mRNA levels in neuronal layers of the hippocampus; however, they resulted in a prono unced induction of trkB mRNA expression in hippocampal non-neuronal ce lls 6-14 d after lesioning. The induction corresponded in time and pla ce to the synaptic reorganization in the lesioned hippocampus. The mRN A species newly induced by the lesions corresponded to those transcrip ts encoding the noncatalytic TrkB receptor isoform that lacks the cyto plasmic protein kinase domain. Expression of mRNAs coding for neurotro phin-3 and the TrkC tyrosine protein kinase were not altered by the le sions. The findings suggest that truncated noncatalytic TrkB molecules expressed on the surface of glial cells play an important role in pla sticity of the adult brain, possibly regulating the concentration of b ioactive neurotrophins or the responsiveness of neurotrophin receptors . Alternatively, they may play a role in presenting neurotrophin molec ules to growing axons.