Schedule of Events | Symposia

Sketchpad Series

Expression of CACNA1C in a circadian mouse model for bipolar disorder

Poster Session C - Sunday, March 30, 2025, 5:00 – 7:00 pm EDT, Back Bay Ballroom/Republic Ballroom

Dennis Arruda¹, Victoria Heimer-McGinn²; ¹Roger Williams University

Cognitive deficits in bipolar disorder (BD) are understudied, undertreated, and poorly understood at the molecular level. In this study, we explore how two putative BD pathologies (circadian function and calcium signaling) may intersect to contribute to cognitive impairment. Both mechanisms have been linked to BD through genetic association studies: the CLOCK gene is a critical component in circadian regulation, while CACNA1C codes for a subunit of a calcium channel that mediates neuronal excitability and intracellular messaging. Both pathways regulate each other, with calcium fluctuations being under circadian control and circadian regulation relying on intracellular calcium signaling. Interestingly, mice with a Clock mutation (ClockΔ19), which display BD-like mood cycling and associated behavioral traits, may also display cognitive impairments in spatial memory (unpublished data from our lab). Finally, CACNA1C is essential for cognitive function. In this study, we quantified the relative expression of CACNA1C mRNA in ClockΔ19 mice (n=3) compared to littermate controls (n=5) using real-time PCR. We also correlated mRNA expression with behavioral data from the novel object location task. Preliminary data indicate no trends in differential mRNA expression between groups. Similarly, behavioral performance does not appear to be correlated to mRNA expression. This suggests that CACNA1C expression may not be related to location memory. Alternatively, considering circadian clocks regulate most bodily functions, it is possible that standard reference genes are not the appropriate control. We are currently in the process of optimizing the assay and clarifying how Clock and calcium mechanisms might intersect to support cognitive function.

Topic Area: LONG-TERM MEMORY: Episodic