An open-source head-fixation and implant-protection system for mice.

Mice are widely used in neuroscience experiments, which often require head-fixation and attachment of skull-mounted hardware. For many experiments, these components must remain intact over weeks to months, ideally with animals group housed. Many labs have designed ad-hoc head-fixation systems, which is an inefficient process. For example, when reinventing these solutions in our lab, we faced challenges with group housing, wherein mice would chew and damage implanted cannulas and electrodes of their cage mates. We performed several non-trivial design iterations to solve this problem, and present the most successful designs as an open-source collection. The designs include a standard mounting headbar compatible with most skull-mounted hardware, a snap-on protective mouse hat (headhat) to prevent mice from chewing the hardware, and a head-fixation station to facilitate common experimental procedures. We provide 3D-printing files, detail vendors and software used to make the components of the system, and provide editable design files for maximum flexibility to individual lab requirements.

Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.

Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons. Chromatin accessibility at enhancers predicted cell-type specific gene regulation, identifying transcriptional mechanisms of differential AMPH responses. Finally, we assessed expression of PV-enriched, AMPH-regulated genes in an Mecp2 mutant mouse strain that shows heightened behavioral sensitivity to psychostimulants to explore the functional importance of this transcriptional program. Together these data provide novel insight into the cell-type specific programs of transcriptional plasticity in NAc neurons that underlie addictive-like behaviors.