Stress induces divergent gene expression among lateral habenula efferent pathways

The ventral pallidum (VP), a major component of the basal ganglia, plays a critical role in motivational disorders. It sends projections to many different brain regions but it is not yet known whether and how these projections differ in their cellular properties, gene expression patterns, connectivity and role in reward seeking. In this study, we focus on four major outputs of the VP - to the lateral hypothalamus (LH), ventral tegmental area (VTA), mediodorsal thalamus (MDT), and lateral habenula (LHb) - and examine the differences between them in 1) baseline gene expression profiles using projection-specific RNA-sequencing; 2) physiological parameters using whole-cell patch clamp; and 3) their influence on cocaine reward using chemogenetic tools. We show that these four VP efferents differ in all three aspects and highlight specifically differences between the projections to the LH and the VTA. These two projections originate largely from separate populations of neurons, express distinct sets of genes related to neurobiological functions, and show opposite physiological and behavioral properties. Collectively, our data demonstrates for the first time that VP neurons exhibit distinct molecular and cellular profiles in a projection-specific manner, suggesting that they represent different cell types.

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Light affects behavioral despair involving the clock gene Period 1

PLoS Genetics ◽

10.1371/journal.pgen.1009625 ◽

2021 ◽

Vol 17 (7) ◽

pp. e1009625

Author(s):

Iwona Olejniczak ◽

Jürgen A. Ripperger ◽

Federica Sandrelli ◽

Anna Schnell ◽

Laureen Mansencal-Strittmatter ◽

...

Keyword(s):

Gene Expression ◽

Clock Gene ◽

Dopaminergic System ◽

Light Therapy ◽

Lateral Habenula ◽

Knock Out ◽

Beneficial Effects ◽

Environmental Light ◽

And Behavior ◽

G Protein Coupled

Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22. In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.

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Divergent gene expression levels between diploid and autotetraploid Tolmiea (Saxifragaceae) relative to the total transcriptome, the cell, and biomass

10.1101/169367 ◽

2017 ◽

Cited By ~ 3

Author(s):

Clayton J. Visger ◽

Gane K-S. Wong ◽

Yong Zhang ◽

Pamela S. Soltis ◽

Douglas E. Soltis

Keyword(s):

Gene Expression ◽

Multiple Scales ◽

Explanatory Power ◽

Transcript Abundance ◽

Differentially Expressed ◽

List Type ◽

Cell Recovery ◽

Biologically Relevant ◽

Divergent Gene ◽

Transcriptome Size

SummaryStudies of gene expression and polyploidy are typically restricted to characterizing differences in transcript concentration. Integrating multiple methods of transcript analysis, we document a difference in transcriptome size, and make multiple comparisons of transcript abundance in diploid and autotetraploid Tolmiea.We use RNA spike-in standards to identify and correct for differences in transcriptome size, and compare levels of gene expression across multiple scales: per transcriptome, per cell, and per biomass.In total, ~17% of all loci were identified as differentially expressed (DEGs) between the diploid and autopolyploid species. A shift in total transcriptome size resulted in only ~58% of the total DEGs being identified as differentially expressed following a per transcriptome normalization. When transcript abundance was normalized per cell, ~82% of the total DEGs were recovered. The discrepancy between per-transcriptome and per-cell recovery of DEGs occurs because per-transcriptome normalizations are concentration-based and therefore blind to differences in transcriptome size.While each normalization enables valid comparisons at biologically relevant scales, a holistic comparison of multiple normalizations provides additional explanatory power not available from any single approach. Notably, autotetraploid loci tend to conserve diploid-like transcript abundance per biomass through increased gene expression per cell, and these loci are enriched for photosynthesis-related functions.

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