Present address: DVV: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Article first published online: 18 APR 2011
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 33, Issue 12, pages 2288–2298, June 2011
How to Cite
Venkitaramani, D. V., Moura, P. J., Picciotto, M. R. and Lombroso, P. J. (2011), Striatal-enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. European Journal of Neuroscience, 33: 2288–2298. doi: 10.1111/j.1460-9568.2011.07687.x
- Issue published online: 20 JUN 2011
- Article first published online: 18 APR 2011
- Received 24 October 2010, revised 1 March 2011, accepted 23 March 2011
- glutamate receptors;
- protein tyrosine phosphatase;
- synaptic plasticity
Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that opposes synaptic strengthening by the regulation of key synaptic signaling proteins. Previous studies suggest a possible role for STEP in learning and memory. To demonstrate the functional importance of STEP in learning and memory, we generated STEP knockout (KO) mice and examined the effect of deletion of STEP on behavioral performance, as well as the phosphorylation and expression of its substrates. Here we report that loss of STEP leads to significantly enhanced performance in hippocampal-dependent learning and memory tasks. In addition, STEP KO mice displayed greater dominance behavior, although they were normal in their motivation, motor coordination, visual acuity and social interactions. STEP KO mice displayed enhanced tyrosine phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2), the NR2B subunit of the N-methyl-d-aspartate receptor (NMDAR) and proline-rich tyrosine kinase (Pyk2), as well as an increased phosphorylation of ERK1/2 substrates. Concomitant with the increased phosphorylation of NR2B, synaptosomal expression of NR1/NR2B NMDARs was increased in STEP KO mice, as was the GluR1/GluR2 containing α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs), providing a potential molecular mechanism for the improved cognitive performance. The data support a role for STEP in the regulation of synaptic strengthening. The absence of STEP improves cognitive performance, and may do so by the regulation of downstream effectors necessary for synaptic transmission.