, 2007). 5-HT also moderates cross-modal plasticity, a procedure of cortical restructuring to compensate for the loss of one sensory system with other intact modalities in the mature brain, specifically among the SSC and visual

system. Increases in extracellular 5-HT in exclusively the rodent barrel cortex following visual deprivation enables synaptic strengthening at layer 4 to layer 2/3 synapses in response to whisker-dependent stimulation of neural activity (Jitsuki et al., 2011). The enhanced transsynaptic signaling efficiency due to AMPA receptor addition to synapses leads to sharpening and fine-tuning of the functional whisker-barrel map at layer 4-2/3 at an age when natural whisker CT99021 chemical structure experience fails to induces synaptic GluR1 delivery. Taken together, sensory deprivation of Selleckchem Ulixertinib one modality increases 5-HT release in remaining modalities, which in turn modulates intracellular signaling pathways involved in AMPA receptor delivery facilitates GluR1-subunit dependent synaptic strengthening, and enables cortical reorganization, thus improving whisker barrel-dependent sensory function. While enhancement of plasticity in response to activation of the 5-HT system has been well-established

by electrophysiological approaches, the underlying molecular mechanisms are now unfolding. Synaptic adhesion molecules and secreted signaling very proteins regulate distinct aspects of neuronal circuitry formation and function. Coordinated actions of a large diversity of molecular signals contribute to the specification and differentiation of synaptic connections in the developing and mature brain. Evidence has been accumulating that 5-HT signaling modulates these adhesion complexes. In this section, we provide a brief overview of synaptic adhesion molecules and their functions. Establishment of functional circuits

and tight regulation of connectivity require precision and specificity of neural wiring at the laminar, cellular, subcellular, and synaptic levels (Williams et al., 2010a). Transmembrane adhesion proteins are essential constituents of synapses that play fundamental roles in building and maintaining synaptic structure during development and serve diverse purposes in synaptic plasticity of the brain throughout the entire life span (Benson et al., 2000; Dalva et al., 2007; Murase and Schuman, 1999; Yamagata et al., 2003). There is a wide diversity of synaptic adhesion molecules and here we discuss only those that have been identified at the crossroads of 5-HT-dependent synaptic plasticity and the pathogenesis of neurodevelopmental disorders. These include integrins, immunoglobulin superfamily (e.g.