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Dystonia is a brain disorder causing involuntary, often painful movements. Apart from a role for dopamine deficiency in some forms, the cellular mechanisms underlying most dystonias are currently unknown. Here, we discover a role for deficient eIF2α signaling in DYT1 dystonia, a rare inherited generalized form, through a genome-wide RNAi screen. Subsequent experiments including patient-derived cells...
The dorsolateral striatum (DLS) is implicated in habit formation. However, the DLS circuit mechanisms underlying habit remain unclear. A key role for DLS is to transform sensorimotor cortical input into firing of output neurons that project to the mutually antagonistic direct and indirect basal ganglia pathways. Here we examine whether habit alters this input-output function. By imaging cortically...
The transcription factor CREB is critical for several forms of experience-dependent plasticity in a range of species and is commonly activated in neurons by calcium/calmodulin-dependent protein kinase IV (CaMKIV). Surprisingly, little is known about the neural circuit adaptations caused by activation of CaMKIV and CREB. Here, we use viral-mediated gene transfer in vivo to examine the consequences...
The active zone protein RIM1α interacts with multiple active zone and synaptic vesicle proteins and is implicated in short- and long-term synaptic plasticity, but it is unclear how RIM1α's biochemical interactions translate into physiological functions. To address this question, we analyzed synaptic transmission in autaptic neurons cultured from RIM1α -/- mice. Deletion of RIM1α...
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