Die Rolle von Neurotrophinen in der Entwicklung und bei der funktionellen Plastizität von Synapsen des Rückenmarks

Neurotrophins are important secreted factors which regulate neuronal survival during development. In recent years it has been found that the newer members of this family, BDNF, NT-3 and NT-4 are can rapidly modulating synaptic efficacy at peripheral and central synapses (Berninger and Poo, 1996; Lewin and Barde, 1996). In this application we will investigate the role of pre-synaptically releases BDNF on the physiological status of primary afferent to spinal cord synapses in mutant mice. Using an in vitro spinal cord preparration from mutant mice the ability of C-fibers nociceptors to induce homo- and heterosynaptic facilitation of the ventral root reflex will be tested. Recently, we have characterized a trk B knock-in mouse where the Shc adaptor proteins cannot bind to the activated kinase receptor. These mice resemble closely NT-4 knockouts in the peripheral nervous system (Minichiello et al. 1998). We want to see if BDNF or NT-4 stimulation of the trk B receptors not signaling via Shc can produce central sensitzation in the spinal cord. In addition we are continuing to develop the gene gun as a device to reintroduce cDNAs of interest into post-mitotic neurons in situ. In addition we will in the next year examine a BDNF promotor knockout where we hope the expression of BDNF is selectively reduced in the peripheral nervous system.

DFG-Verfahren Schwerpunktprogramme

Teilprojekt zu SPP 1026:  Molekulare Physiologie der synaptischen Interaktion: Analyse in definierten Säugetiermutanten