Biology subjects

Susic, M.

Publications and source records attributed to Susic, M..

4 recordsLinked to original sources

bioRxiv2026

Rhythmic expression of a cAMP phosphodiesterase switches neuronal excitability states in the mammalian suprachiasmatic nucleus

How the transcriptome of a neuron determines its electrophysiological properties and how this change in different contexts are major questions in neurobiology. The intracellular molecular clocks in the circadian pacemaker neurons in the mammalian suprachiasmatic nucleus (SCN) drive 24hr rhythms in clock gene expression via a transcriptional-translational feedback loop1,2. These molecular clocks also control 24hr rhythms in the firing of SCN neurons3-5 - a subset of which enter a silent depolarized state around midday6. We used single-cell RNA sequencing and identified that the Avp / Nms and Vip / Nms are the SCN neurons that undergo daytime silencing. We also found high level and rhythmic expression of the Pde10a phosphodiesterase in these Nms SCN neurons. Acutely inhibiting Pde10a activity or elevating intracellular cAMP - to bypass high Pde10a levels - specifically shifts these Nms+ SCN neurons into a depolarized silent state hours ahead of schedule. A similar mechanism may occur in other neurons that switch to silent depolarized states.

neuroscience↗

bioRxiv2025

Distinct depressive-like behavioural phenotypes in mice exhibit unique patterns of transcriptional perturbations across habenular cell subtypes

Major depressive disorder arises from diverse neurobiological mechanisms, yet how specific habenular cell types contribute to distinct depressive-like behaviours remains unclear. Using chronic social defeat stress, behavioural phenotyping, and single-cell RNA sequencing, we mapped stress-induced transcriptional changes across habenular cell types and lateral habenula (LHb) subregions. Our findings reveal that each behavioural phenotype is marked by its own transcriptional profile. These subregion-specific patterns across the LHb suggest that different cellular circuits contribute uniquely to depressive-like states.

neuroscience↗

bioRxiv2023

Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

The molecular mechanisms that link stress and circadian rhythms still remain unclear. The habenula (Hb) is a key brain region involved in regulating diverse types of emotion-related behaviours while the suprachiasmatic nucleus (SCN) is the bodys central clock. To investigate the effects of chronic social stress on transcription patterns, we performed gene expression analysis in the Hb and SCN of stress naive and stress exposed mice. Our analysis revealed a large number of differentially expressed genes and enrichment of synaptic and cell signalling pathways between resilient and stress-naive mice at ZT16 in both the Hb and SCN. This transcriptomic signature was nighttime-specific and observed only in stress-resilient mice. In contrast, there were relatively few differences between the stress-susceptible and stress-naive groups across timepoints. Our results reinforce the functional link between diurnal gene expression patterns and differential responses to stress, thereby highlighting the importance of temporal expression patterns in homeostatic stress responses.

neuroscience↗

bioRxiv2023

Chronic social stress blunts core body temperature and molecular rhythms of Cirbp and Rbm3 in mice lateral habenula

Chronic social stress in mice causes behavioral and physiological changes that result in perturbed rhythms of body temperature, activity and sleep-wake cycle. To further understand the link between mood disorders and temperature rhythmicity in mice that are resilient or susceptible to stress, we measured core body temperature (Tcore) before and after exposure to chronic social defeat stress (CSDS). We found that Tcore amplitudes of stress-resilient and susceptible mice are dampened during exposure to CSDS. However, following CSDS, resilient mice recovered temperature amplitude faster than susceptible mice. Furthermore, the interdaily stability (IS) of temperature rhythms was fragmented in stress-exposed mice during CSDS, which recovered to control levels following stress. There were minimal changes in locomotor activity after stress exposure which correlates with regular rhythmic expression of Prok2 - an output signal of the suprachiasmatic nucleus. We also determined that expression of thermosensitive genes Rbm3 and Cirbp in the lateral habenula (LHb) were blunted 1-day after CSDS. Rhythmic expression of these genes recovered 10 days later. Overall, we show that CSDS blunts Tcore and thermosensitive gene rhythms. Tcore rhythm recovery is faster in stress-resilient mice, but Rbm3 and Cirbp recovery is uniform across the phenotypes.

neuroscience↗