Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice

Protein tyrosine phosphatase delta (PTP delta) is a receptor-type PTP expressed in the specialized regions of the brain including the hippocampal CA2 and CA3, B lymphocytes and thymic medulla. To elucidate the physiological roles of PTP delta, PTP delta-deficient mice were produced by gene targeting. It was found that PTP delta-deficient mice were semi-lethal due to insufficient food intake. They also exhibited learning impairment in the Morris water maze, reinforced T-maze and radial arm maze tasks. Interestingly, although the histology of the hippocampus appeared normal, the magnitudes of long-term potentiation (LTP) induced at hippocampal CA1 and CA3 synapses were significantly enhanced in PTP delta-deficient mice, with augmented paired-pulse facilitation in the CA1 region. Thus, it was shown that PTP delta plays important roles in regulating hippocampal LTP and learning processes, and that hippocampal LTP does not necessarily positively correlate with spatial learning ability. To our knowledge, this is the first report of a specific PTP involved in the regulation of synaptic plasticity or in the processes regulating learning and memory.