animals display reduced GEF activity, dendritic arborization and spine density. These deficits may be linked to the observed reductions in prepulse inhibition, sociability and increased locomotor activity. Notably, loss of kalirin results in deficits in working memory, but not reference memory. The generation of a kalirin7 specific knockout animal model revealed similar deficits in spine density, suggesting a central role of kalirin7 in regulating neuronal connectivity. Both full and kalirin7 specific knockout animals show decreased anxiety-like behavior and impaired contextual fear learning. Expression Multiple isoforms, arising from alternate splicing and promoter usage, display varying tissue and developmental expression. Control over kalirin expression is exerted through the use of alternate promoters which produce alternate start sites and restrict expression to specific neuronal subpopulations, and alter kalirin activity within neurons. During early development, the long kalirin9 and 12 isoforms are predominant in the brain. These isoforms contain both a Rac and a RhoA selective GEF domain, and control axonal growth and dendritic branching. Kalirin9 and 12 are also expressed ubiquitously throughout the body and have functions outwith the brain. However, during neurodevelopment the kalirin7 isoform is preferentially expressed during periods of synaptogenesis, and this isoform displays highly restricted cortical expression. Kalirin7 expresses only the N-terminal domains, including the Rac-GEF domain along with a c-terminal PDZ-binding domain that strongly targets kalirin7 to the post-synaptic density. It is likely this subcellular distribution is vital to kalirin7 function, as this isoform exerts control dendritic spine density and synaptic plasticity. It is likely that mutations that result in deregulation of kalirin function within the brain is responsible for the role of kalirin within multiple neurological disorders. Notes References External links Traffic jam in brain causes schizophrenia symptoms Architect of Synaptic Plasticity Links Spine Form and Function - Schizophrenia Research Forum, 2007-11-30 EC 2.7.11 GTP-binding protein regulators