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

Abstract

1. Protein tyrosine phosphorylation is thought to play an important role in the regulation of neuronal function. Previous work has shown that protein tyrosine kinase (PTK) inhibitors can inhibit the induction of long-term potentiation (LTP), a candidate synaptic mechanism involved in memory formation. However, how PTK activity might contribute to LTP induction remains elusive. To understand the role of PTK pathways in the development of LTP better, a set of studies was implemented in area CA1 of rat hippocampal slices using both intra- and extracellular recordings. We show here that bath application or injection into postsynaptic cells of the PTK inhibitors genistein 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 effectively blocked LTP. However, application at 10 or 30 min after induction had no detectable effect on potentiation. 3. PTK inhibitor pretreatment did not affect the long-lasting enhancement of synaptic response produced by phorbol 12,13-dibutyrate (PDBu), forskolin plus 3-isobutyl-L-methylxanthine (IBMX), or tetraethylammonium (TEA). In contrast, PTK inhibitors significantly blocked postanoxic LTP. 4. EPQ(pY)EEIPIA, an activator of Src family PTKs, produced a gradual and robust increase in the synaptic response and occluded LTP. 5. These results suggest that Src family kinases are potential candidates for the PTKs contributing to the molecular mechanism of LTP induction at Schaffer collateral-CA1 synapses.