Babenko, V. | bioRxiv Science

bioRxiv2019

Dopamine response gene pathways in dorsal striatum MSNs from a gene expression viewpoint: cAMP-mediated gene networks

A mouse model of chronic social conflicts was used to analyze dorsal striatum neurons implicated in cAMP-mediated phosphorylation activation pathways specific for Medium Spiny Neurons (MSNs). Based on expression correlation analysis, we succeeded in dissecting Drd1- and Drd2-dopaminoceptive neurons (D1 and D2, correspondingly) gene pathways. We also found that D1 neurons feature previously reported two states, passive and active ones, represented in our analysis by distinct, negatively correlated gene clusters.\n\nThe correlation based gene pathways strongly corroborate the phosphorylation cascades highlighted in the previous studies, implying that the expression-based viewpoint corresponds to phosphorylation/dephosphorylation interplay in each type of neurons. Notably, D2 neurons showed the largest Ppp1r1b (encoding DARPP-32) expression modulation impact, implying that Ppp1r1b expression dynamics is mostly associated with neuroendocrine response mediated by Penk/Pdyn genes expression in D2 neurons.\n\nWe observed that under defeat stress in chronic social conflicts mice exhibited reduced motor activity as well as overall depression of dopamine-mediated MSNs activity, while aggressive mice exhibited motor hyperactivity and an increase in both D1-active phase and D2 MSNs genes expression.\n\nBased on alternative transcript isoforms expression analysis, it was assumed that many genes (Drd1, Adora1, Pde10, Ppp1r1b, Gnal), specifically those in D1 neurons, apparently remain transcriptionally repressed via the reversible mechanism of promoter CpG island silencing, resulting in alternative promoter usage following profound reduction in their expression rate.\n\nSignificance statementMedium Spiny Neurons (MSNs) comprise the main body of dorsal striatum neurons and represent dopaminoceptive GABAergic neurons. The cAMP- mediated cascade of excitation and inhibition responses involved in dopaminergic neurotransmission is crucial for neuroscience research due to its involvement in the motor and behavioral functions. In particular, all types of addictions are related to MSNs. Shedding the light on the mechanics of the above-mentioned cascade is of primary importance for this research domain. In this paper MSNs steady states will be elucidated based on pooled tissue RNA-Seq data not explicitly outlined before and connected with dynamic dopamine neurotransmission cycles.

neuroscience↗

bioRxiv2019

Sympathetic and parasympathetic involvement in time constrained sequential foraging

Appraising sequential offers relative to an unknown future opportunity and a time cost requires an optimization policy that draws on a learned estimate of an environments richness. Converging evidence points to a learning asymmetry, whereby estimates of this richness update with a bias toward integrating positive information. We replicate this bias in a sequential foraging (prey selection) task and probe associated activation within two branches of the autonomic system, sympathetic and parasympathetic branches, using trial-by-trial measures of simultaneously recorded cardiac autonomic physiology. In general, lower value offers were accepted during periods of autonomic drive, both in the sympathetic (shorter pre-ejection period PEP) and parasympathetic (higher HF HRV) branches. In addition, we reveal a unique adaptive role for the sympathetic branch in learning. It was specifically associated with adaptation to a deteriorating environment: it correlated with both the rate of negative information integration in belief estimates and downward changes in moment-to-moment environmental richness, and was predictive of optimal performance on the task. The findings are consistent with a parallel processing framework whereby autonomic function serves both learning and executive demands of prey selection.\n\nSignificance statementThe value of choices (accepting a job) depends on context (richness of the current job market). Learning contexts, therefore, is crucial for optimal decision-making. Humans demonstrate a bias when learning contexts; we learn faster about improvements vs deteriorations. New techniques allow us to cleanly measure fast acting stress responses that might fluctuate with trial-by-trial learning. Using these new methods, we observe here that increased stress - specifically sympathetic (heart contractility) - might help overcome the learning bias (making us faster at learning contextual deterioration) and thereafter guide us toward better context appropriate decisions. For the first time we show that specific building blocks of good decision-making might benefit from short bursts of specific inputs of the stress system.

physiology↗