Protein tyrosine kinase is required for the induction of long-term potentiation in the rat hippocampus

1. Protein tyrosine phosphorylation is thought to play an important rob in the regulation of neuronal function. Previous work has shown that protein t yrosine kinase (PTK) inhibitors can inhibit the induction of long-term pote ntiation (LTP), a candidate synaptic mechanism involved in memory formation . However, how PTK activity might contribute to LTP induction remains elusi ve. To understand the role of PTK. pathways in the development of LTP bette r, a set of studies was implemented in area CA1. of rat hippocampal slices using both intra- and extracellular recordings. We show here that bath appl ication or injection into postsynaptic cells of the PTK inhibitors genistei n and lavendustin A blocked the induction of LTP produced by high-frequency tetanic stimulation. 2. Application of lavendustin A 10 min before or 3 min after induction effe ctively blocked LTP. However, application at 10 or 30 min after induction h ad no detectable effect on potentiation. 3. PTK inhibitor pretreatment did not affect the long-lasting enhancement o f synaptic response produced by phorbol 12,13-dibutyrate (PDBu), forskolin plus 3-isobutyl-L-methyl-xanthine (IBMX), or tetraethylammonium (TEA). In c ontrast, PTK inhibitors significantly blocked postanoxic LTP. 4. EPQ(pY)EEIPIA, an activator of Src family PTKs, produced a gradual and r obust increase in the synaptic response and occluded LTP. 5. These results suggest that Src family kinases are potential candidates f or the PTKs contributing to the molecular mechanism of LTP induction at Sch affer collateral-CA1 synapses.