Ania Busza

Interactions between Circadian Neurons Control Temperature Synchronization of Drosophila Behavior

Most animals rely on circadian clocks to synchronize their physiology and behavior with the day/night cycle. Light and temperature are the major physical variables that can synchronize circadian rhythms. Although the effects of light on circadian behavior have been studied in detail in Drosophila, the neuronal mechanisms underlying temperature synchronization of circadian behavior have received less attention. Here, we show that temperature cycles synchronize and durably affect circadian behavior in Drosophila in the absence of light input. This synchronization depends on the well characterized and functionally coupled circadian neurons controlling the morning and evening activity under light/dark cycles: the M cells and E cells. However, circadian neurons distinct from the M and E cells are implicated in the control of rhythmic behavior specifically under temperature cycles. These additional neurons play a dual role: they promote evening activity and negatively regulate E cell function in the middle of the day. We also demonstrate that, although temperature synchronizes circadian behavior more slowly than light, this synchronization is considerably accelerated when the M cell oscillator is absent or genetically altered. Thus, whereas the E cells show great responsiveness to temperature input, the M cells and their robust self-sustained pacemaker act as a resistance to behavioral synchronization by temperature cycles. In conclusion, the behavioral responses to temperature input are determined by both the individual properties of specific groups of circadian neurons and their organization in a neural network.

Retraction: PER-TIM Interactions with the Photoreceptor Cryptochrome Mediate Circadian Temperature Responses in Drosophila.

Drosophila cryptochrome (CRY) is a key circadian photoreceptor that interacts with the period and timeless proteins (PER and TIM) in a light-dependent manner. We show here that a heat pulse also mediates this interaction, and heat-induced phase shifts are severely reduced in the cryptochrome loss-of-function mutant cryb. The period mutant perL manifests a comparable CRY dependence and dramatically enhanced temperature sensitivity of biochemical interactions and behavioral phase shifting. Remarkably, CRY is also critical for most of the abnormal temperature compensation of perL flies, because a perL; cryb strain manifests nearly normal temperature compensation. Finally, light and temperature act together to affect rhythms in wild-type flies. The results indicate a role for CRY in circadian temperature as well as light regulation and suggest that these two features of the external 24-h cycle normally act together to dictate circadian phase.

Thalamus segmentation based on the local diffusion direction: A group study

Fast and accurate segmentation of deep gray matter regions in the brain is important for clinical applications such as surgical planning for the placement of deep brain stimulation implants. Mapping anatomy from stereotactic atlases to patient data is problematic because of individual differences in subject anatomy that are not accounted for by commonly used atlases. We present a segmentation method for individual subject diffusion tensor MR data that is based on local diffusion information to identify subregions of the thalamus. We show the correspondence of our segmentation results to anatomy by comparison with stereotactic atlas data. Importantly, we verify the consistency of our segmentation by evaluating the method on 63 healthy volunteers. Our method is fast, reliable, and independent of any segmentation before the classification of regions within the thalamus. It should, therefore, be useful in clinical applications. Magn Reson Med, 2011.

Calcium and SOL Protease Mediate Temperature Resetting of Circadian Clocks.

Summary Circadian clocks integrate light and temperature input to remain synchronized with the day/night cycle. Although light input to the clock is well studied, the molecular mechanisms by which circadian clocks respond to temperature remain poorly understood. We found that temperature phase shifts Drosophila circadian clocks through degradation of the pacemaker protein TIM. This degradation is mechanistically distinct from photic CRY-dependent TIM degradation. Thermal TIM degradation is triggered by cytosolic calcium increase and CALMODULIN binding to TIM and is mediated by the atypical calpain protease SOL. This thermal input pathway and CRY-dependent light input thus converge on TIM, providing a molecular mechanism for the integration of circadian light and temperature inputs. Mammals use body temperature cycles to keep peripheral clocks synchronized with their brain pacemaker. Interestingly, downregulating the mammalian SOL homolog SOLH blocks thermal mPER2 degradation and phase shifts. Thus, we propose that circadian thermosensation in insects and mammals share common principles.

Retraction Notice to: Calcium and SOL Protease Mediate Temperature Resetting of Circadian Clocks

(Cell 163, 1214–1224; November 19, 2015)In the above article, we presented evidence that temperature phase shifts animal circadian clocks through regulated degradation of critical circadian pacemaker proteins mediated by calcium and SOL protease. In follow-up experiments, other members of the corresponding author’s laboratory were unable to reproduce key observations made in vivo that supported the role of calcium and SOL protease in signaling temperature input to the Drosophila circadian clock. An in-depth review of the dataset generated by the first author revealed clear evidence that he had repeatedly misrepresented and altered primary data pertaining to the role of calcium, calmodulin, and SOL protease in Drosophila during the study. An independent investigation conducted by the University of Massachusetts Medical School concluded that the first author committed scientific misconduct. Since the manipulated data—which measured the amplitude of circadian phase shifts in response to temperature pulses in various genotypes using luciferase and behavioral assays—were critical to support our conclusions, we are retracting the above article. We sincerely apologize to the scientific community for publishing this erroneous article and profoundly regret any inconvenience and confusion that it might have caused.The first author, Ozgur Tataroglu, declined to sign this retraction.

Clinical Reasoning: A 32-year-old woman with right-sided numbness and word-finding difficulties

A 32-year-old right-handed woman from El Salvador was brought into the emergency department (ED) because of confusion, right-sided numbness, and word-finding difficulties.