Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.05.08.592609

Sex differences in change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex

Abstract

Changing ones mind involves re-appraisals between past-costs versus future-value and may be altered in psychopathology. Long intergenic non-coding RNA LINC00473 in medial prefrontal cortex (mPFC) can induce stress-resilience in a sex-dependent manner, but its role in cognition is unknown. We characterized decision-making behavior in male and female mice in the neuroeconomic paradigm Restaurant Row following virus-mediated expression of LINC00473 in mPFC. Mice foraged for food among varying temporal-costs and subjective-value while on a limited time-budget. Without affecting primary deliberative decisions, LINC00473 selectively influenced re-evaluative choices in a sex-dependent manner. This included changing how mice (i) cached value with the passage of time and (ii) weighed prior mistakes, which underlie the computational bases of sensitivity to sunk costs and regret. These findings suggest a common value function is shared between these neuroeconomic processes and reveal a bridge between molecular drivers of stress-resilience and psychological mechanisms underlying sex-specific proclivities in negative rumination.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Durand-de Cuttoli, R., Issler, O., Yakubov, B., Jahan, N., Abid, A., Kasparov, S., Granizo, K., Ahmed, S., Russo, S. J., Nestler, E. J., Sweis, B. M.. 2024-05-08. Sex differences in change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex. https://doi.org/10.1101/2024.05.08.592609

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A Mechanistic Account of Dedifferentiation in the Aging Visual System

To uncover the mechanisms of age-related dedifferentiation, we simulated neural degradation in a computational model of the ventral visual stream. Severing connections or adding noise, whether in inferotemporal cortex (IT) or upstream, reduced IT differentiation, indicating that dedifferentiation need not originate locally. Degrading peripheral V1, which preferentially drove place-selective IT neurons, selectively reduced place differentiation, a candidate mechanism for the stronger place dedifferentiation reported in aging.

neuroscience↗

Reusing pipettes in Patch-seq: a foundation for automated multimodal profiling

Patch-seq is a technique for single-cell multimodal characterization. It combines whole-cell electrophysiology, single-cell transcriptomics, and morphological reconstruction in single neurons. Patch-seq morphologies are a critical bridge among cell types, genes, physiology, and large-scale connectivity platforms such as EM connectomes and single-cell-resolution projectomes. However, patch-seq experimental complexity and operator dependence limit throughput. Automation could enable scalable Patch-seq but requires procedural adaptations, including detergent-based pipette cleaning, robotic nucleus extraction and collection. The impact of these automations on Patch-seq quality has not been systematically evaluated. Here, we show that each of these modifications preserves or improves key Patch-seq outcomes. Automated nucleus extraction performs comparably to, or better than, expert manual operation, preserving key RNA and morphological metrics. Detergent-cleaned, reused pipettes supported a viable sealing success rate across multiple cleaning cycles and preserved electrophysiological quality and transcriptomic yield without introducing excess contamination. Sonication effectively allows collection of nuclear material without damaging RNA and supports subsequent pipette cleaning and reuse. Enhanced automated sealing and break-in procedures increased throughput regardless of brain region, cell type or species. Together, these results validate the core procedural adaptations required for automated Patch-seq and establish a foundation for high-throughput, standardized multimodal single-cell characterization.

neuroscience↗

Development of direction selectivity in the Xenopus tadpole optic tectum and midbrain tegmentum

Detecting motion direction is a fundamental function performed by direction selective (DS) neurons. DS neurons in the optic tectum (superior colliculus in mammals) enable the tracking of moving objects. DS neurons of the accessory optic system support reflexive eye / head movements that stabilize gaze during self-motion. By developmental stage 48 (10 days postfertilization), Xenopus tadpoles display visually guided behaviors that require both types of DS neurons. Our previous work has shown that these two regions are not only functionally distinct but also follow different developmental programs. Here we characterized and compared how direction selectivity develops in both visual processing centers. Using in vivo electrophysiological recordings during moving bar visual stimulation, we measured DS synaptic inputs and spiking outputs in both regions across three key developmental stages of the retinotectal projection. Tegmental neurons were direction selective ab initio, and both input and output tuning remained stable across development. Tectal neurons were observed to receive DS inputs early, and their input selectivity also remained stable across development. However, their spiking output grew substantially more DS at the later developmental stage. This was due at least in part to a naturally occurring decrease in intrinsic excitability which preferentially dampened overall spike rates, but especially in response to the non-preferred direction of motion, thereby increasing direction selectivity. These results reveal distinct developmental trajectories in parallel visual pathways. Tegmental direction selectivity is established early and stays stable, whereas tectal output tuning sharpens during development through a decrease in intrinsic excitability.

neuroscience↗