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The Journal of Neuroscience, July 6, 2005, 25(27):6296-6303; doi:10.1523/JNEUROSCI.0506-05.2005

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Behavioral/Systems/Cognitive
cAMP Responsive Element-Binding Protein Phosphorylation Is Necessary for Perirhinal Long-Term Potentiation and Recognition Memory

E. Clea Warburton,¹ Colin P. J. Glover,² Peter V. Massey,¹ Humin Wan,¹ Ben Johnson,¹ Alison Bienemann,² Ule Deuschle,⁴ James N. C. Kew,⁴ John P. Aggleton,³ Zafar I. Bashir,¹ James Uney,² and Malcolm W. Brown¹

¹Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1 TD, United Kingdom, ²The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Bristol BS1 3NY, United Kingdom, ³School of Psychology, University of Cardiff, Cardiff CF10 3YG, United Kingdom, and ⁴Preclinical CNS Research, F. Hoffmann-La Roche, CH-4070 Basel, Switzerland

We established the importance of phosphorylation of cAMP responsive element-binding protein (CREB) to both the familiarity discrimination component of long-term recognition memory and plasticity within the perirhinal cortex of the temporal lobe. Adenoviral transduction of perirhinal cortex (and adjacent visual association cortex) with a dominant-negative inhibitor of CREB impaired the preferential exploration of novel over familiar objects at a long (24 h) but not a short (15 min) delay, disrupted the normal reduced activation of perirhinal neurons to familiar compared with novel pictures, and impaired long-term potentiation of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for involvement of CREB phosphorylation in synaptic plastic processes within perirhinal cortex necessary for long-term recognition memory.

Key words: temporal lobe; plasticity; familiarity discrimination; viral transduction; hippocampus; Fos

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Received Feb 7, 2005; revised May 9, 2005; accepted May 17, 2005.

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