No abstract

Impulsive behavior during adolescence may stem from developmental imbalances between motivational and cognitive-control systems, producing greater urges to pursue reward and weakened capacities to inhibit such actions. Here, we developed a Pavlovian-instrumental transfer (PIT) protocol to assay rats’ ability to suppress cue-motivated reward seeking based on changes in reward expectancy. Traditionally, PIT studies focus on how reward-predictive cues motivate instrumental reward-seeking behavior (lever pressing). However, cues signaling imminent reward delivery also elicit countervailing focal-search responses (food-port entry). We first examined how reward expectancy (cue-reward probability) influences expression of these competing behaviors. Adult male rats increased rates of lever pressing when presented with cues signaling lower probabilities of reward but focused their activity at the food cup on trials with cues that signaled higher probabilities of reward. We then compared adolescent and adult male rats in their responsivity to cues signaling different reward probabilities. In contrast to adults, adolescent rats did not flexibly adjust patterns of responding based on the expected likelihood of reward delivery but increased their rate of lever pressing for both weak and strong cues. These findings indicate that control over cue-motivated behavior is fundamentally dysregulated during adolescence, providing a model for studying neurobiological mechanisms of adolescent impulsivity.

No abstract

Massively-parallel single-cell and single-nucleus RNA sequencing (scRNA-seq, snRNA-seq) requires extensive sequencing to achieve proper per-cell coverage, making sequencing resources and availability of sequencers critical factors for conducting deep transcriptional profiling. CoolMPS is a novel sequencing-by-synthesis approach that relies on nucleotide labeling by re-usable antibodies, but whether it is applicable to snRNA-seq has not been tested. Here, we use a low-cost and off-the-shelf protocol to chemically convert libraries generated with the widely-used Chromium 10X technology to be sequenceable with CoolMPS technology. To assess the quality and performance of converted libraries sequenced with CoolMPS, we generated a snRNA-seq dataset from the hippocampus of young and old mice. Native libraries were sequenced on an Illumina Novaseq and libraries that were converted to be compatible with CoolMPS were sequenced on a DNBSEQ-400RS. CoolMPS-derived data faithfully replicated key characteristics of the native library dataset, including correct estimation of ambient RNA-contamination, detection of captured cells, cell clustering results, spatial marker gene expression, inter- and intra-replicate differences and gene expression changes during aging. In conclusion, our results show that CoolMPS provides a viable alternative to standard sequencing of RNA from droplet-based libraries.