Axon growth is an essential cellular process during neural development, and its dysregulation contributes to numerous neurodevelopmental disorders. During axon growth, extracellular signals direct neu Show more
Axon growth is an essential cellular process during neural development, and its dysregulation contributes to numerous neurodevelopmental disorders. During axon growth, extracellular signals direct neurons to extend projections that connect with their synaptic targets. Paxillin is a key member of adhesion sites that control motility by linking the intracellular actin cytoskeleton to the extracellular matrix. Paxillin also binds to the cytoskeletal protein, tubulin. However, little is known about the role of adhesion proteins in neurons. Here, we use conditional paxillin knockout mice to investigate how loss of paxillin in pyramidal cortical neurons affects developing neuron morphology. Surprisingly, loss of paxillin in pyramidal cortical neurons caused no change in axon length or soma area between control ( Show less
The orbitofrontal cortex (OFC) is a vital component of brain reward circuitry that is important for reward seeking behavior. However, OFC-mediated molecular mechanisms underlying rewarding behavior ar Show more
The orbitofrontal cortex (OFC) is a vital component of brain reward circuitry that is important for reward seeking behavior. However, OFC-mediated molecular mechanisms underlying rewarding behavior are understudied. Here, we report the first circular RNA (circRNA) profile associated with appetitive reward and identify regulation of 92 OFC circRNAs by sucrose self-administration. Among these changes, we observed downregulation of circNrxn3, a circRNA originating from neurexin 3 (Nrxn3), a gene involved in synaptogenesis, learning, and memory. Transcriptomic profiling via RNA sequencing and qPCR of the OFC following in vivo knock-down of circNrxn3 revealed differential regulation of genes associated with pathways important for learning and memory and altered splicing of Nrxn3. Furthermore, circNrxn3 knock-down enhanced sucrose self-administration and motivation for sucrose. Using RNA-immunoprecipitation, we report binding of circNrxn3 to the known Nrxn3 splicing factor SAM68. circNrxn3 is the first reported circRNA capable of regulating reward behavior and circNrxn3-mediated interactions with SAM68 may impact subsequent downstream processing of RNAs such as the regulation of gene expression and splicing. Show less