| First Author | Horwood JM | Year | 2004 |
| Journal | Behav Brain Res | Volume | 150 |
| Issue | 1-2 | Pages | 127-38 |
| PubMed ID | 15033286 | Mgi Jnum | J:95936 |
| Mgi Id | MGI:3528115 | Doi | 10.1016/S0166-4328(03)00248-1 |
| Citation | Horwood JM, et al. (2004) Evidence for disrupted NMDA receptor function in tissue plasminogen activator knockout mice. Behav Brain Res 150(1-2):127-38 |
| abstractText | Tissue plasminogen activator (tPA), a serine protease immediate-early gene product expressed in brain areas important in learning and memory, has been shown to cleave the NR1 subunit of the NMDA receptor leading to a potentiated Ca(2+) influx. Mice lacking tPA (tPA-/- mice) have disrupted late phase-LTP in the hippocampus, possibly as a consequence of reduced Ca(2+) flux through NMDA receptors. In the present experiments, we investigated whether the NMDA antagonist dizocilpine might alter performance in tPA-/- mice in behavioural tasks shown to be sensitive to hippocampal lesions. tPA-/- mice and wild-type controls (WT) showed similar rates of acquisition and performance of a spatial working memory task (eight-arm radial maze). Dizocilpine (0.03-0.3 mg/kg, i.p.), given acutely, disrupted performance by increasing the number of errors equally across both genotypes. At asymptotic performance of a differential reinforcement of low response rate operant task (DRL), acute dizocilpine (0.03-0.3 mg/kg) impaired performance, but no differences between genotypes were observed. However, dizocilpine (0.1 mg/kg), given repeatedly during acquisition of a signalled-DRL15' task, retarded acquisition in tPA-/- but not WT mice. This treatment regime had no effect on locomotor activity in either genotype. tPA-/- mice showed no spatial learning deficits, but were more sensitive to dizocilpine during acquisition (though not expression) of a DRL task. This supports a role for tPA in modification of the NMDA receptor, although absence of tPA does not have consequences for all forms of NMDA-dependent mediated learning. |
