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...

It is often claimed that tools are embodied by their user, but whether the brain actually repurposes its body-based computations to perform similar tasks with tools is not known. A fundamental computation for localizing touch on the body is trilateration. Here, the location of touch on a limb is computed by integrating estimates of the distance between sensory input and its boundaries (e.g., elbow and wrist of the forearm). As evidence of this computational mechanism, tactile localization on a limb is most precise near its boundaries and lowest in the middle. Here, we show that the brain repurposes trilateration to localize touch on a tool, despite large differences in initial sensory input compared with touch on the body. In a large sample of participants, we found that localizing touch on a tool produced the signature of trilateration, with highest precision close to the base and tip of the tool. A computational model of trilateration provided a good fit to the observed localization behavior. To further ...

During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In the olfactory bulb, a mitral cell initially extends multiple dendrites to multiple glomeruli but eventually forms a single primary dendrite through the activity-dependent dendrite pruning process. Recent studies have reported that microglia facilitate synapse pruning during the circuit remodeling in some systems. It has remained unclear whether microglia are involved in the activity-dependent dendrite pruning in the developing brains. Here, we examined whether microglia are required for the developmental dendrite pruning of mitral cells in mice. To deplete microglia in the fetal brain, we treated mice with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% in mice treated with PLX5622. However, dendrite pruning of mitral cells was not significantly affec...

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...

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...

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...

Highlighted Research Paper: [[T. Moldwin, M. Kalmenson, and I. Segev, “Asymmetric voltage attenuation in dendrites can enable hierarchical heterosynaptic plasticity.” eNeuro (2023).][2]][2] []: /lookup/doi/10.1523/ENEURO.0014-23.2023

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 …

Plaque formation, microglial activation, and synaptic loss are pathological hallmarks of Alzheimer's disease, however, removing plaques have had little clinical benefit. Here, we show that neuregulin-1, a glial growth factor, induces inflammatory cytokines and promotes phagocytic activity in vitro and augments microglial activation and plaque formation in 5XFAD Alzheimer’s mice. Brain-specific targeting of neuregulin-1 by intraventricular delivery of a novel neuregulin-1 fusion protein antagonist GlyB4 significantly alters microglial morphology and function to a non-pathogenic morphology in early-stage 5XFAD mice and prevents plaques from forming. Once plaques have already formed, GlyB4 reduces new plaque formation and prevents synaptic loss. Selective, targeted disruption of neuregulin-1 signaling on brain microglia with GlyB4 could be a novel ‘upstream’ approach to slow or stop disease progression in Alzheimer’s disease. Significance Statement Microglia-associated neuroinflammation is a major hallmark...

During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In the olfactory bulb, a mitral cell initially extends multiple dendrites to multiple glomeruli but eventually forms a single primary dendrite through the activity-dependent dendrite pruning process. Recent studies have reported that microglia facilitate synapse pruning during the circuit remodeling in some systems. It has remained unclear whether microglia are involved in the activity-dependent dendrite pruning in the developing brains. Here, we examined whether microglia are required for the developmental dendrite pruning of mitral cells in mice. To deplete microglia in the fetal brain, we treated mice with a CSF1R inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% in mice treated with PLX5622. However, dendrite pruning of mitral cells was not significantly affected. Moreover, we found no significant ...