A study of transsynaptic signalling in the hippocampus : a role for nerve growth factor?

Abstract

Long-term potentiation (LTP) is perhaps the best described form of synaptic plasticity. This project aimed to investigate the role that tyrosine kinases play in the expression of LTP in dentate gyrus-granule cell synapses in vivo and to establish whether nerve growth factor (NGF) modulates this. The focus of this study has been on presynaptic changes which accompany LTP in dentate gyrus, in particular, glutamate release which is enhanced in association with LTP. Although it has been known for several years that LTP expression is blocked if tyrosine kinase activity is inhibited the mechanisms underlying this were not known. The data obtained from this study shows that tyrosine kinase inhibitors decreased both glutamate release and influx implying a presynaptic action of tyrosine kinases. The factor which initiates such tyrosine kinase activity may be NGF as the results presented in this study indicate that tyrphostin AG879, an inhibitor of trk, blocked LTP while NGF stimulates trkA in vitro.