bims-ciryme 2023-11-19 papers

Curr Biol. 2023 Nov 06. pii: S0960-9822(23)01425-2. [Epub ahead of print]

A time memory engram embedded in a light-entrainable circadian clock.

David E Ehichioya, S K Tahajjul Taufique, Sofia Farah, Shin Yamazaki.

A longstanding mystery in chronobiology is the location and molecular mechanism of the food-entrainable oscillator (FEO).1,2,3 The FEO is an enigmatic circadian pacemaker that controls food anticipatory activity (FAA). The FEO is implicated as a circadian oscillator that entrains to feeding time. However, the rhythmic properties of the FEO remain a mystery in part due to technical limitations in distinguishing FAA from locomotor activity controlled by the primary circadian pacemaker in the suprachiasmatic nucleus (SCN). To overcome this limitation, we used the Feeding Experimentation Device version 3 (FED3) to measure food-seeking, nose-poking behavior. When food availability was limited to 4 h at night, mice exhibited strong anticipatory nose-poking behavior prior to mealtime. When food availability was moved to the daytime, mice quickly expressed daytime anticipatory nose pokes without displaying transients. Unexpectedly, the mice also maintained nighttime anticipatory nose pokes, even though food pellets were no longer dispensed at night. We next tested if food anticipation was directly encoded on a light-entrainable oscillator by shifting the light-dark cycle without changing mealtime. Anticipatory behavior shifted in parallel with the light-dark cycle, although meal timing was unchanged. Next, we tested whether encoding meal timing for anticipatory nose pokes required a functional SCN by studying Period 1/2/3 triple knockout mice with disabled SCN. Food anticipatory nose poking of Period knockout mice shifted in parallel with the light-dark cycle independent of a functional SCN clock. Our data suggest that food anticipation time is embedded in a novel, extra-SCN light-entrainable oscillator.

Keywords: calorie restriction; circadian mutant mice; entrainment; extra-SCN circadian pacemaker; food anticipation; food-seeking behavior; operant chamber; restricted feeding; reward; wheel-running activity

DOI: https://doi.org/10.1016/j.cub.2023.10.027

Commun Biol. 2023 11 11. 6(1): 1149

Cardiomyocyte-specific disruption of the circadian BMAL1-REV-ERBα/β regulatory network impacts distinct miRNA species in the murine heart.

Mary N Latimer, Lamario J Williams, Gobinath Shanmugan, Bryce J Carpenter, Mitchell A Lazar, Pieterjan Dierickx, Martin E Young.

Circadian disruption increases cardiovascular disease (CVD) risk, through poorly understood mechanisms. Given that small RNA species are critical modulators of cardiac physiology/pathology, we sought to determine the extent to which cardiomyocyte circadian clock (CCC) disruption impacts cardiac small RNA species. Accordingly, we collected hearts from cardiomyocyte-specific Bmal1 knockout (CBK; a model of CCC disruption) and littermate control (CON) mice at multiple times of the day, followed by small RNA-seq. The data reveal 47 differentially expressed miRNAs species in CBK hearts. Subsequent bioinformatic analyses predict that differentially expressed miRNA species in CBK hearts influence processes such as circadian rhythmicity, cellular signaling, and metabolism. Of the induced miRNAs in CBK hearts, 7 are predicted to be targeted by the transcriptional repressors REV-ERBα/β (integral circadian clock components that are directly regulated by BMAL1). Similar to CBK hearts, cardiomyocyte-specific Rev-erbα/β double knockout (CM-RevDKO) mouse hearts exhibit increased let-7c-1-3p, miR-23b-5p, miR-139-3p, miR-5123, and miR-7068-3p levels. Importantly, 19 putative targets of these 5 miRNAs are commonly repressed in CBK and CM-RevDKO heart (of which 16 are targeted by let-7c-1-3p). These observations suggest that disruption of the circadian BMAL1-REV-ERBα/β regulatory network in the heart induces distinct miRNAs, whose mRNA targets impact critical cellular functions.

DOI: https://doi.org/10.1038/s42003-023-05537-z

Nat Neurosci. 2023 Nov 13.

AgRP neurons encode circadian feeding time.

Nilufer Sayar-Atasoy, Iltan Aklan, Yavuz Yavuz, Connor Laule, Hyojin Kim, Jacob Rysted, Muhammed Ikbal Alp, Debbie Davis, Bayram Yilmaz, Deniz Atasoy.

Food intake follows a predictable daily pattern and synchronizes metabolic rhythms. Neurons expressing agouti-related protein (AgRP) read out physiological energetic state and elicit feeding, but the regulation of these neurons across daily timescales is poorly understood. Using a combination of neuron dynamics measurements and timed optogenetic activation in mice, we show that daily AgRP-neuron activity was not fully consistent with existing models of homeostatic regulation. Instead of operating as a 'deprivation counter', AgRP-neuron activity primarily followed the circadian rest-activity cycle through a process that required an intact suprachiasmatic nucleus and synchronization by light. Imposing novel feeding patterns through time-restricted food access or periodic AgRP-neuron stimulation was sufficient to resynchronize the daily AgRP-neuron activity rhythm and drive anticipatory-like behavior through a process that required DMHPDYN neurons. These results indicate that AgRP neurons integrate time-of-day information of past feeding experience with current metabolic needs to predict circadian feeding time.

DOI: https://doi.org/10.1038/s41593-023-01482-6