The holy grail of longevity research.

A new technology to study physiology and cognition elevates African turquoise killifish as a model organism for studies of aging in vertebrates.

HOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring.

The body plan of animals is laid out by an evolutionary-conserved HOX code which is colinearly transcribed after zygotic genome activation (ZGA). Here we report that SMCHD1, a chromatin-modifying enzyme needed for X-inactivation in mammals, is maternally required for timely HOX expression. Using zebrafish and mouse Smchd1 knockout animals, we demonstrate that Smchd1 haplo-insufficiency brings about precocious and ectopic HOX transcription during oogenesis and embryogenesis.

Oxytocin receptors influence the development and maintenance of social behavior in zebrafish (Danio rerio).

Zebrafish are highly social teleost fish and an excellent model to study social behavior. The neuropeptide Oxytocin is associated different social behaviors as well as disorders resulting in social impairment like autism spectrum disorder. However, how Oxytocin receptor signaling affects the development and expression kinetics of social behavior is not known.

Contingent stimulus delivery assay for zebrafish reveals a role for CCSER1 in alcohol preference.

Alcohol use disorders are complex, multifactorial phenomena with a large footprint within the global burden of diseases. Here, we report the development of an accessible, two-choice self-administration zebrafish assay (SAZA) to study the neurobiology of addiction. Using this assay, we first demonstrated that, although zebrafish avoid higher concentrations of alcohol, they are attracted to low concentrations.

A novel zebrafish model for intermediate type spinal muscular atrophy demonstrates importance of Smn for maintenance of mature motor neurons.

A deficiency in Survival Motor Neuron (SMN) protein results in motor neuron loss in spinal muscular atrophy (SMA) patients. Human SMN is encoded by SMN1 and SMN2 that differ by a single C6T transition in a splice regulatory region of exon 7. In SMN2, exon 7 is skipped leading to an unstable protein, which cannot compensate for SMN1 loss in SMA patients.

Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila.

Many organs and tissues have an intrinsic ability to regenerate from a dedicated, tissue-specific stem cell pool. As organisms age, the process of self-regulation or homeostasis begins to slow down with fewer stem cells available for tissue repair. Tissues become more fragile and organs less efficient.

Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study.

Genetics intersects with environmental, cultural, and social factors in the development of addictive disorders. This study reports the feasibility of whole-exome sequencing of trios (subject and two family members) to discover potential genetic variants in the development of substance use disorders (SUD). Family trios were recruited from the National Addictions Management Service in Singapore during the 2016-2018 period.

Use of Optogenetic Amyloid-β to Monitor Protein Aggregation in and .

Alzheimer's Disease (AD) has long been associated with accumulation of extracellular amyloid plaques (Aβ) originating from the Amyloid Precursor Protein. Plaques have, however, been discovered in healthy individuals and not all AD brains show plaques, suggesting that extracellular Aβ aggregates may play a smaller role than anticipated. One limitation to studying Aβ peptide during disease progression is the inability to induce aggregation in a controlled manner.

A Neurexin2aa deficiency results in axon pathfinding defects and increased anxiety in zebrafish.

Neurexins are presynaptic transmembrane proteins that control synapse activity and are risk factors for autism spectrum disorder. Zebrafish, a popular model for behavioral studies, has six neurexin genes, but their functions in embryogenesis and behavior remain largely unknown. We have previously reported that nrxn2a is aberrantly spliced and specifically dysregulated in motor neurons (MNs) in models of spinal muscular atrophy.

Neural correlates of state transitions elicited by a chemosensory danger cue.

Background: Detection of predator cues changes the brain state in prey species and helps them avoid danger. Dysfunctionality in changing the central state appropriately in stressful situations is proposed to be an underlying cause of multiple psychiatric disorders in humans.

Methods: Here, we investigate the dynamics of neural circuits mediating response to a threat, to characterize these states and to identify potential control networks.

Total Recall: Lateral Habenula and Psychedelics in the Study of Depression and Comorbid Brain Disorders.

Depression impacts the lives and daily activities of millions globally. Research into the neurobiology of lateral habenula circuitry and the use of psychedelics for treating depressive states has emerged in the last decade as new directions to devise interventional strategies and therapies. Several clinical trials using deep brain stimulation of the habenula, or using ketamine, and psychedelics that target the serotonergic system such as psilocybin are also underway.

Design, challenges, and the potential of transcriptomics to understand social behavior.

Rapid advances in Ribonucleic Acid sequencing (or RNA-seq) technology for analyzing entire transcriptomes of desired tissue samples, or even of single cells at scale, have revolutionized biology in the past decade. Increasing accessibility and falling costs are making it possible to address many problems in biology that were once considered intractable, including the study of various social behaviors. RNA-seq is opening new avenues to understand long-standing questions on the molecular basis of behavioral plasticity and individual variation in the expression of a behavior.

Why behavioral neuroscience still needs diversity?: A curious case of a persistent need.

In the past few decades, a substantial portion of neuroscience research has moved from studies conducted across a spectrum of animals to reliance on a few species. While this undoubtedly promotes consistency, in-depth analysis, and a better claim to unraveling molecular mechanisms, investing heavily in a subset of species also restricts the type of questions that can be asked, and impacts the generalizability of findings. A conspicuous body of literature has long advocated the need to expand the diversity of animal systems used in neuroscience research.

Application of optogenetic Amyloid-β distinguishes between metabolic and physical damages in neurodegeneration.

The brains of Alzheimer's disease patients show a decrease in brain mass and a preponderance of extracellular Amyloid-β plaques. These plaques are formed by aggregation of polypeptides that are derived from the Amyloid Precursor Protein (APP). Amyloid-β plaques are thought to play either a direct or an indirect role in disease progression, however the exact role of aggregation and plaque formation in the aetiology of Alzheimer's disease (AD) is subject to debate as the biological effects of soluble and aggregated Amyloid-β peptides are difficult to separate in vivo.

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids.

Computational geometric tools for quantitative comparison of locomotory behavior.

A fundamental challenge for behavioral neuroscientists is to accurately quantify (dis)similarities in animal behavior without excluding inherent variability present between individuals. We explored two new applications of curve and shape alignment techniques to address this issue. As a proof-of-concept we applied these methods to compare normal or alarmed behavior in pairs of medaka (Oryzias latipes).

An Automated Assay System to Study Novel Tank Induced Anxiety.

New environments are known to be anxiogenic initially for many animals including the zebrafish. In the zebrafish, a novel tank diving (NTD) assay for solitary fish has been used extensively to model anxiety and the effect of anxiolytics. However, studies can differ in the conditions used to perform this assay.

Modeling Alzheimer's and Other Age Related Human Diseases in Embryonic Systems.

Modeling human disease in animals is an important strategy to discover potential methods of intervention. We suggest that there is much to be gained by employing a multi-model approach that takes advantage of different animal systems used in the laboratory simultaneously. We use the example of modeling Alzheimer's disease in , , and to illustrate how such an approach can be employed to investigate the pathophysiology of the disease.

A little rein on addiction.

Rewarding and aversive experiences influence emotions, motivate specific behaviors, and modify future action in animals. Multiple conserved vertebrate neural circuits have been discovered that act in a species-specific manner to reinforce behaviors that are rewarding, while attenuating those with an adverse outcome. A growing body of research now suggests that malfunction of the same circuits is an underlying cause for many human disorders and mental ailments.

Conspecific injury raises an alarm in medaka.

In the late 1930s, Karl von Frisch reported that semiochemicals released upon injury, act as alarm substances (Schreckstoff) in fish. In Ostariophysi species, club cells in the epidermis are believed to contain cues related to alarm substance; however, the function of club cells, primarily as reservoirs of alarm substance has been debated. Here, I describe an alarm response in the Japanese rice fish Oryzias latipes (medaka), a member of the order Beloniformes.

The right dorsal habenula limits attraction to an odor in zebrafish.

Background: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays.