Mitochondria are integrative hubs central to cellular adaptive pathways. Such pathways are critical in highly differentiated postmitotic neurons, the plasticity of which sustains brain function. Consequently, defects in mitochondria and in their dynamics appear instrumental in neurodegenerative diseases and may also participate in cognitive impairments. To directly test this hypothesis, we analyzed cognitive performances in a mouse mitochondria-based disease model, because of haploinsufficiency in the mitochondrial optic atrophy type 1 (OPA1) protein involved in mitochondrial dynamics. In males, we evaluated adult hippocampal neurogenesis parameters using immunohistochemistry. We performed a battery of tests to assess basal behavioral characteristics and cognitive performances, and tested putative treatments. While in dominant optic atrophy (DOA) mouse models, the known main symptoms are late onset visual deficits, we discovered early impairments in hippocampus-dependent spatial memory attributable to defe...

Because of the legalization of Cannabis in many jurisdictions and the trend of increasing Δ9-tetrahydrocannabinol (THC) content in Cannabis products, an urgent need exists to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we exposed female Sprague Dawley rats to Cannabis smoke daily from gestational day 6 to 20 or room air. Maternal reproductive parameters, offspring behavior, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis -exposed litters. In adulthood, male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantl...

The detection of a single photon by a rod photoreceptor is limited by two sources of physiological noise, called discrete and continuous noise. Discrete noise occurs as intermittent current deflections with a waveform very similar to that of the single-photon response to real light and is thought to be produced by spontaneous activation of rhodopsin. Continuous noise occurs as random and continuous fluctuations in outer-segment current and is usually attributed to some intermediate in the phototransduction cascade. To confirm the origin of these noise sources, we have recorded from retinas of mouse lines with rods having reduced levels of rhodopsin, transducin, or phosphodiesterase. We show that the rate of discrete noise is diminished in proportion to the decrease in rhodopsin concentration, and that continuous noise is independent of transducin concentration but clearly elevated when the level of phosphodiesterase is reduced. Our experiments provide new molecular evidence that discrete noise is indeed pr...

I am always marveled by the brain’s vast capabilities. Each discovery, each revelation, seems to open a door only to reveal myriad others yet unopened. The brain, with its vast intricacies, consistently reminds us that its complexity transcends the limits of our imagination. It is in this spirit that I wish to introduce “Brain Mysteries: Complexity Beyond Imagination” in eNeuro . All neuroscientists have been contributing for decades to the mapping of brain networks and to the unraveling of its codes. While every stride has been fruitful in terms …

Neuroscientists endeavor to unravel the mysteries of brain functions and dysfunctions. A common research strategy involves measuring specific parameters across various conditions. These measurements are then typically repeated, averaged, and used to infer general patterns or rules. The act of averaging data is an ancient practice; for instance, early astronomers in Babylonian, Chinese, and Indian cultures implicitly averaged observations of celestial phenomena to predict significant periods, such as those crucial for agriculture. Averaging is a sound approach when the process being studied follows to a mathematical function, represented as y = f(x), where f is a very general function. This is true even if the exact function is not known at the outset of the experiments. Implicit in this method is the assumption that any variations in measurements arise from imperfections in the recording process since a consistent mathematical rule suggests that identical inputs should always yield the same output. In ess...

Real science is not only about “the data” but also about theoretical, sociological, economic, and political matters. Reflecting on the struggles of the ongoing adversarial collaboration to test theories of consciousness, here I suggest to “ask not what neuroscience can do for consciousness but what consciousness can do for neuroscience.” “Big fish: Aren’t these waters fascinating and treacherous? Small fish: What waters?” – Anonymous Richard Feynman is notorious for his witty quotes, including that “philosophy of science is about as useful to scientists as ornithology is to birds.” Indeed, some neuroscientists would look perplexed in front of analytic accounts of their own practices, methods, and foundations. Starlings fly by flapping their feathered wings and yet, regardless of their individual skills and collective choreographies, they may be ignorant about how and why they do it. A tweet-long crash course in philosophy of science could suffice to realize that binary thinking (“Is it true or not?”) co...

Every so often, I conclude that life is not possible. It is not uncommon for me to walk out of a seminar about the pathways and dynamics of biochemical signaling or the structure of biological molecules to conclude that the complexities of life processes defy imagination. Our ability to maintain a sense of wonder about the mysteries of biological mechanisms is what drives us as scientists, as otherwise wresting new insights from the recalcitrant world of interacting pathways would be too frustrating. So all successful biologists must, paradoxically, see both the proverbial forest and their trees, and recognize both the elegant simplicity and the confounds characteristic of living organisms. That sense of mystery and wonder is somewhat at odds with our common sense. It is common sense that is now too often lost, as we grapple with new technologies and large datasets in our science. As scientists, today, we must balance our common sense with our growing reliance on big data to extract the new insights about...

The sensory system allows humans to not only explore the world but also to monitor their own bodies for injury and disease through the sensation of pain. After an injury, signals from the injured tissues travel along the nerves, entering the central nervous system through the spinal cord before going into the brain. In the acute stages, pain modulates behavior in ways that promote healing, including limiting mobility. In most cases, pain resolves as the injury heals, but, in some cases, pain persists and becomes chronic. Chronic pain is a massive issue, affecting up to 20% of Americans and leading to reduced quality of life for those affected. The factors leading to chronic pain are complex, and new approaches are needed to improve understanding of chronic pain and find effective treatments. In the current issue of eNeuro , Haroun et al. (2023) use a new approach to transiently silence sensory neurons in uninjured mice as well as mouse models of acute and chronic pain using a technique known as chemogenet...

Animals exhibit context-dependent behavioral decisions that are mediated by specific motor circuits. In social species these decisions are often influenced by social status. Although social status-dependent neural plasticity of motor circuits has been investigated in vertebrates, little is known of how cellular plasticity translates into differences in motor activity. Here, we used zebrafish ( Danio rerio ) as a model organism to examine how social dominance influences the activation of swimming and the Mauthner mediated startle escape behaviors. We show that the status-dependent shift in behavior patterns whereby dominants increase swimming and reduce sensitivity of startle escape while subordinates reduce their swimming and increase startle sensitivity is regulated by the synergistic interactions of dopaminergic, glycinergic and GABAergic inputs to shift the balance of activation of the underlying motor circuits. This shift is driven by socially induced differences in expression of dopaminergic receptor ...

During the development of the cerebral cortex, N-cadherin plays a crucial role in facilitating radial migration by enabling cell-to-cell adhesion between migrating neurons and radial glial fibers or Cajar–Reztius cells. ADP ribosylation factor 4 (Arf4) and Arf5, which belong to the Class II Arf small GTPase subfamily, control membrane trafficking in the endocytic and secretory pathways. However, their specific contribution to cerebral cortex development remains unclear. In this study, we sought to investigate the functional involvement of Class II Arfs in radial migration during the layer formation of the cerebral cortex using mouse embryos and pups. Our findings indicate that knock-down of Arf4, but not Arf5, resulted in the stalling of transfected neurons with disorientation of the Golgi in the upper intermediate zone (IZ) and reduction in the migration speed in both the IZ and cortical plate (CP). Migrating neurons with Arf4 knock-down exhibited cytoplasmic accumulation of N-cadherin, along with disturb...