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Biology subjects

Appelbaum, L.

Publications and source records attributed to Appelbaum, L..

8 recordsLinked to original sources

Artificial light at night reshapes diel brain transcriptomics in Dascyllus aruanus damselfish

Artificial light at night (ALAN) disrupts natural light cycles and interferes with light-dependent biological processes. However, the effect of ALAN on cellular processes in wildlife is unclear. We examined diel brain transcriptomic alterations in the diurnal damselfish Dascyllus aruanus by comparing fish exposed to three consecutive nights of ALAN with control fish, sampled during both the day and night. ALAN partially disrupted circadian regulation transcription, altering diel expression of the core clock regulator bmal1 and glucocorticoid-regulated genes. At night, ALAN triggered activation of genes indicative of neuronal activity and acute neural stress, along with suppression of restorative nocturnal processes. The following day, the transcriptomic divergence between ALAN-exposed and control fish expanded, with widespread downregulation of genes governing vascular homeostasis, coagulation, and immune function. Together, these findings indicate that ALAN reshapes brain transcriptomic programs across the entire diel cycle, identifying molecular signatures of physiological disruption in light-polluted marine environments.

cell biology↗

Red light mitigates ALAN-induced memory impairment in the clownfish Amphiprion ocellaris

Artificial light at night (ALAN) is an increasingly pervasive anthropogenic pollutant in coastal ecosystems. However, its effects on brain function and behaviour in reef fishes remain poorly understood. Here, we investigated the impact of ALAN on learning and memory in the clownfish, Amphiprion ocellaris, a diurnal reef fish with well-characterised photoreceptive systems. Cognitive performance was assessed using a colour discrimination task following exposure to ALAN of varying intensities and spectral compositions. ALAN impaired learning and memory after only two consecutive nights of exposure, with effects emerging at intensities as low as 0.5 lux. At higher intensities (5-50 lux), memory was consistently disrupted under white-cool, white-warm, blue, and green LED light, whereas red light had no detectable effect. Together, these findings demonstrate that ALAN rapidly alters cognitive performance in clownfish and that these effects are strongly wavelength-dependent. Our results highlight the vulnerability of diurnal reef-associated fishes to nocturnal light pollution and underscore the need for ecologically informed lighting strategies that use longer-wavelength red-emitting light sources to reduce both the intensity and spectral impact of ALAN in coastal environments.

animal behavior and cognition↗

Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

Dysregulation of sleep has widespread health consequences and represents an enormous health burden. Short-sleeping individuals are predisposed to the effects of neurodegeneration, suggesting a critical role for sleep in the maintenance of neuronal health. While the effects of sleep on cellular function are not completely understood, growing evidence has identified an association between sleep loss and DNA damage, raising the possibility that sleep facilitates efficient DNA repair. The Mexican tetra fish, Astyanax mexicanus provides a model to investigate the evolutionary basis for changes in sleep and the consequences of sleep loss. Multiple cave-adapted populations of these fish have evolved to sleep for substantially less time compared to surface populations of the same species without identifiable impacts on healthspan or longevity. To investigate whether the evolved sleep loss is associated with DNA damage and cellular stress, we compared the DNA Damage Response (DDR) and oxidative stress levels between A. mexicanus populations. We measured markers of chronic sleep loss and discovered elevated levels of the DNA damage marker {gamma}H2AX in the brain, and increased oxidative stress in the gut of cavefish, consistent with chronic sleep deprivation. Notably, we found that acute UV-induced DNA damage elicited an increase in sleep in surface fish but not in cavefish. On a transcriptional level, only the surface fish activated the photoreactivation repair pathway following UV damage. These findings suggest a reduction of the DDR in cavefish compared to surface fish that coincides with elevated DNA damage in cavefish. To examine DDR pathways at a cellular level, we created an embryonic fibroblast cell line from the two populations of A. mexicanus. We observed that both the DDR and DNA repair were diminished in the cavefish cells, corroborating the in vivo findings and suggesting that the acute response to DNA damage is lost in cavefish. To investigate the long-term impact of these changes, we compared the transcriptome in the brain and gut of aged surface fish and cavefish. Strikingly, many genes that are differentially expressed between young and old surface fish do not transcriptionally vary by age in cavefish. Taken together, these findings suggest that cavefish have developed resilience to sleep loss, despite possessing cellular hallmarks of chronic sleep deprivation.

neuroscience↗

Venom tradeoff shapes interspecific interactions, physiology and reproduction

The ability of an animal to effectively capture prey and defend against predators is pivotal for its survival. Venom, a mixture of many toxin proteins, shapes predator-prey interactions. Here, we use the sea anemone Nematostella vectensis to test how toxin genotypes impact predator-prey interactions. We developed a new genetic manipulation tool which significantly reduces both RNA and protein levels of Nv1, a major neurotoxin. In concert we recently discovered a native population of Nematostella that has lost Nv1.We demonstrate that these anemones lacking Nv1, have reduced ability to defend themselves against grass shrimp, a native predator. Additionally, secreted Nv1 can act indirectly in defense by attracting mummichog fish, which are known to prey on grass shrimp. This unravels a tritrophic interaction acting in animal defense at the molecular level. Additionally, our work reveals an evolutionary tradeoff, as the reduction of Nv1 levels causes faster growth and increased sexual and asexual reproductive rates.

evolutionary biology↗

Uncovering the function of the evolutionary conserved Clock gene in the sea anemone Nematostella vectensis

The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL or pacemaker) with CLOCK as a conserved positive factor in animals. However, CLOCKs functional evolutionary origin and mechanism of action in basal animals are unknown. In the cnidarian Nematostella vectensis, pacemaker gene transcript levels, including NvClk (the Clock ortholog), appear arrhythmic under constant darkness, questioning the role of NvCLK. Utilizing CRISPR/Cas9, we generated a NvClk allele mutant (NvClk{Delta}), revealing circadian behavior loss in constant light conditions (LL and DD) while a 24-hour rhythm was maintained under light-dark condition (LD). Transcriptomics showed distinct rhythmic genes in wild-type (WT) genes in LD compared to DD. The LD NvClk{Delta}/{Delta} showed comparable numbers of rhythmic genes, but were greatly reduced in DD. Furthermore, the LD NvClk{Delta}/{Delta} showed alterations in temporal pacemaker gene expression, affecting their potential interactions. Additionally, differential expression of non-rhythmic genes associated with cell division and neuronal differentiation was observed. These findings revealed that a light-responsive pathway can partially compensate for circadian clock disruption and that the Clock gene has evolved in cnidarians to synchronize rhythmic physiology and behavior to the diel rhythm of the earths biosphere.

evolutionary biology↗

Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex

Despite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the underlying mechanisms-of-actions that mediate modulatory effects remain poorly understood. To fill this gap, we studied dose-response functions of TMS for modulation of visual processing. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During participants first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions. TMS effects on VEPs showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal dose-response relationships between intensity and timing of TMS on visual perception and electrophysiological brain activity, generally indicating greater facilitation at stimulation intensities below RMT.

neuroscience↗

Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior

The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general. Alternative splicing of PAC1 results in multiple gene products, which differ in their mode of signalling and tissue distribution. However, the roles of distinct splice variants in the regulation of stress behavior is poorly understood. Alternative splicing of a short exon, which is known as the "hop cassette", occurs during brain development and in response to stressful challenges. To examine the function of this variant, we generated a splice-specific zebrafish mutant lacking the hop cassette, which we designated hopless. We show that hopless mutant larvae display increased anxiety-like behavior, including reduced dark exploration and impaired habituation to dark exposure. Conversely, adult hopless mutants displayed superior ability to rebound from an acute stressor, as they exhibited reduced anxiety- like responses to an ensuing novelty stress. We propose that the developmental loss of a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the long term, predisposes the organisms stress response towards a resilient phenotype. Our study presents a unique genetic model demonstrating how early-life state of anxiety paradoxically correlates with reduced stress susceptibility in adulthood.

animal behavior and cognition↗

Cavefish brain atlases reveal functional and anatomical convergence across independently evolved populations

Environmental perturbation can drive the evolution of behavior and associated changes in brain structure and function. The generation of computationally-derived whole-brain atlases have provided insight into neural connectivity associated with behavior in many model systems. However, these approaches have not been used to study the evolution of brain structure in vertebrates. The Mexican tetra, A. mexicanus, comprises river-dwelling surface fish and multiple independently evolved populations of blind cavefish, providing a unique opportunity to identify neuroanatomical and functional differences associated with behavioral evolution. We employed intact brain imaging and image registration on 684 larval fish to generate neuroanatomical atlases of surface fish and three different cave populations. Analyses of brain regions and neural circuits associated with behavioral regulation identified convergence on hypothalamic expansion, as well as changes in transmitter systems including elevated numbers of catecholamine and hypocretin neurons in cavefish populations. To define evolutionarily-derived changes in brain function, we performed whole brain activity mapping associated with feeding and sleep. Feeding evoked neural activity in different sensory processing centers in surface and cavefish. We also identified multiple brain regions with sleep-associated activity across all four populations, including the rostral zone of the hypothalamus and tegmentum. Together, these atlases represent the first comparative brain-wide study of intraspecies variation in a vertebrate model, and provide a resource for studying the neural basis underlying behavioral evolution.

neuroscience↗