¹Department of Psychiatry and Center for Basic Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA

Correspondence: Dr EJ Nestler, Department of Psychiatry, Center for Basic Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9070, USA. Tel: +214 648 1111, Fax: +214 648 4947; E-mail: Eric.Nestler@utsouthwestern.edu

Received 23 April 2007; Revised 26 June 2007; Accepted 22 July 2007; Published online 29 August 2007.

Abstract

Plasticity in the brain is important for learning and memory, and allows us to respond to changes in the environment. Furthermore, long periods of stress can lead to structural and excitatory changes associated with anxiety and depression that can be reversed by pharmacological treatment. Drugs of abuse can also cause long-lasting changes in reward-related circuits, resulting in addiction. Each of these forms of long-term plasticity in the brain requires changes in gene expression. Upon stimulation, second messenger pathways are activated that lead to an enhancement in transcription factor activity at gene promoters. This stimulation results in the expression of new growth factors, ion channels, structural molecules, and other proteins necessary to alter the neuronal circuit. With repeated stimulation, more permanent modifications to transcription factors and chromatin structure are made that result in either sensitization or desensitization of a circuit. Studies are beginning to uncover the molecular mechanisms that lead to these types of long-term changes in the brain. This review summarizes some of the major transcriptional mechanisms that are thought to underlie neuronal and behavioral plasticity.