News & Views

Recent genome editing techniques have substantially simplified the generation of genetically modified mice. A new study combines adeno-associated viruses (AAV) and electroporation to generate a robust pipeline to deliver CRISPR-Cas reagents into mouse embryos.

No, we are not talking about a new dish for dinner, but a study representing an emerging research field. Psilocybin research is gaining momentum, and zebrafish behavioral neuroscience research has been exponentially expanding. At the intersection of these two research fields is a recent paper that utilized high-tech video-tracking to detect behavioral changes induced by this psychoactive drug in larval zebrafish.

Unlocking the secrets of the brain requires high precision tools to record neuronal activity. Neuroscientists have tools to capture neuronal activity with unprecedented speed, precision and fidelity. Thanks to a ground-breaking redesign of the linker peptide of GCaMP proteins, a domain seldomly considered for optimization, a new sensor bridges the gap between calcium imaging and electrophysiology.

A recent study performed directed C5-cytosine methylation of CpG islands to demonstrate that acquired methylation at critical loci could be reestablished for multiple generations in mice. This work provides a manipulatable system to examine how non-genetic information is transmitted across generations to regulate complex phenotypes.

New research using high-dimensional behavioural analyses has further undermined the “females are the more variable sex” trope that often accompanies all-male studies. But when we consider the benefits to the inclusion of females in research, their lesser variability is only the icing on the cake. It’s just good science, really.

Despite centuries of effort from philosophers, physicians and biologists, the answer to the seemingly simple question “what is aging?” remains elusive. Some even posit that aging represents a phenomenon too expansive to ever be succinctly defined. A new study tackles this question by profiling hundreds of phenotypes across age in mice and examining how the trajectories of these phenotypes are altered by geroprotective genetic and dietary interventions.

A challenge in translational research is comparing behaviors across species. A new study combines a novel behavioral paradigm in rats and humans with reinforcement learning to infer shared computations for goal-directed navigation.

The application of genome-editing tools to generate point mutations in animal models is of particular value for precise disease modeling, but the PAM requirement of Cas enzymes is a critical limiting factor. Two new studies demonstrate that SpRY variant displays efficient genome editing in a nearly PAM-less manner in zebrafish, expanding the targeting scope of base editors in this model.

Single nucleotide polymorphisms in the FKBP5 gene influence the risk of developing stress-related disorders, but the underlying processes are not fully understood. Animal models offer a possibility to investigate the influence of FKBP5 gene variants on the stress response system.

New insights into gut-brain axis and cognition function show that accumulation of Caudovirales bacteriophages in the gut microbiota is associated with improved executive function and memory.

Rodent grooming is an important behaviour that is commonly used to characterize preclinical models of human brain disorders. A new paper has leveraged deep learning to develop a precise, high throughput and automated grooming classifier to facilitate mechanistic neuroscience research on grooming.

Social isolation can lead to poor mental and physical health. A new study determines that social isolation increases food and nicotine-seeking during abstinence, but that social housing can reverse these effects.

A new CRISPR/Cas9 method that can generate F0 mutant zebrafish has the potential to cut costs, spare time, and reduce animal use for researchers interested in screening loss-of-function alleles in vivo.

To achieve knockdown rather than knockout of particular genes, a new paper demonstrates a CRISPR/Cas13 method that can efficiently edit mRNA in zebrafish, medaka, killifish, and mouse embryos.

Cortico-striatal circuits are at the heart of many brain disorders, which means they are often studied using neurobiological animal models. A new study uses resting-state functional connectivity to assess homologies of cortico-striatal circuits in mice, monkeys, and humans.

Caged neurotransmitters are widely used to study neurobiological processes such as synaptic transmission and plasticity. However, uncaging has been primarily restricted to in vitro and ex vivo experimental systems. Using caged neurotransmitters in vivo has posed a huge hurdle because photoactivatable cages bind to GABA-A receptors, acting as competitive antagonists towards GABA. This reduced inhibition leads to epileptiform-like activity, which can cause problems for circuit level studies in vivo. To circumvent this off-target effect, a recent publication introduces a new caged glutamate: G5-MNI-glutamate. Using a novel technique called ‘cloaking,’ GABA-A receptor antagonism is abolished, opening up new possibilities for future in vivo studies with caged neurotransmitters.

Vasculature has an essential role both in central nervous system health and diseases. A new optimized imaging and analysis pipeline helps to characterize blood vessel network topology and plasticity across large regions in detail.

Human cancer is a disease of cooperating genetic events that is complex to model in vivo. A new study combines somatic base editing with a mouse model of breast cancer, demonstrating the potential to rapidly investigate the function of disease-specific point mutations.

Microglia play important but incompletely understood roles in the pathogenesis of neurological disease. New chimeric models using transplanted human stem cell-derived microglia-like cells hold great promise to better model the unique function of human microglia in brain disease.