Early changes in spatiotemporal dynamics of remapped circuits and global networks predict functional recovery after stroke in mice.

Significance: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

Aim: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.

Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked.

Concurrent optogenetic motor mapping of multiple limbs in awake mice reveals cortical organization of coordinated movements.

Background: Motor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution.

Spatiotemporal relationships between neuronal, metabolic, and hemodynamic signals in the awake and anesthetized mouse brain.

Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.

Resting-state MRI reveals spontaneous physiological fluctuations in the kidney and tracks diabetic nephropathy in rats.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion.

Introduction to the Optics and the Brain 2023 feature issue.

A feature issue is being presented by a team of guest editors containing papers based on contributed submissions including studies presented at Optics and the Brain, held April 24-27, 2023 as part of Optica Biophotonics Congress: Optics in the Life Sciences, in Vancouver, Canada.

Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring.

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity.

Arousal as a universal embedding for spatiotemporal brain dynamics.

Neural activity in awake organisms shows widespread and spatiotemporally diverse correlations with behavioral and physiological measurements. We propose that this covariation reflects in part the dynamics of a unified, arousal-related process that regulates brain-wide physiology on the timescale of seconds. Taken together with theoretical foundations in dynamical systems, this interpretation leads us to a surprising prediction: that a single, scalar measurement of arousal (e.

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice.

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect.

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity.

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections.

Wide-Field Optical Imaging in Mouse Models of Ischemic Stroke.

Functional neuroimaging is a powerful tool for evaluating how local and global brain circuits evolve after focal ischemia and how these changes relate to functional recovery. For example, acutely after stroke, changes in functional brain organization relate to initial deficit and are predictive of recovery potential. During recovery, the reemergence and restoration of connections lost due to stroke correlate with recovery of function.

Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke.

Understanding circuit-level manipulations that affect the brain's capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g.

Normal aging in mice is associated with a global reduction in cortical spectral power and network-specific declines in functional connectivity.

Normal aging is associated with a variety of neurologic changes including declines in cognition, memory, and motor activity. These declines correlate with neuronal changes in synaptic structure and function. Degradation of brain network activity and connectivity represents a likely mediator of age-related functional deterioration resulting from these neuronal changes.

STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks.

Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer's disease (AD)-related pathology. For in vitro experiments, human brain vascular smooth muscle cells (HBVSMC) and human brain microvascular endothelial cells (HBMEC) were used, and these cultured cells were exposed to Aβ peptides followed by measurement of activated forms of STAT3 expression and reactive oxygen species (ROS) generation.

Opposed hemodynamic responses following increased excitation and parvalbumin-based inhibition.

Understanding cellular contributions to hemodynamic activity is essential for interpreting blood-based brain mapping signals. Optogenetic studies examining cell-specific influences on local hemodynamics have reported that excitatory activity results in cerebral perfusion and blood volume increase, while inhibitory activity contributes to both vasodilation and vasoconstriction. How specific subpopulations of interneurons regulate the brain's blood supply is less examined.

In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring.

The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion.

Electrically coupled inhibitory interneurons constrain long-range connectivity of cortical networks.

Spontaneous infra-slow brain activity (ISA) exhibits a high degree of temporal synchrony, or correlation, between distant brain regions. The spatial organization of ISA synchrony is not explained by anatomical connections alone, suggesting that active neural processes coordinate spontaneous activity. Inhibitory interneurons (IINs) form electrically coupled connections via the gap junction protein connexin 36 (Cx36) and networks of interconnected IINs are known to influence neural synchrony over short distances.

Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks.

Electrophysiological recordings have established that GABAergic interneurons regulate excitability, plasticity, and computational function within local neural circuits. Importantly, GABAergic inhibition is focally disrupted around sites of brain injury. However, it remains unclear whether focal imbalances in inhibition/excitation lead to widespread changes in brain activity.

Separability of calcium slow waves and functional connectivity during wake, sleep, and anesthesia.

Modulation of brain state, e.g., by anesthesia, alters the correlation structure of spontaneous activity, especially in the delta band.

Circadian clock protein Rev-erbα regulates neuroinflammation.

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation.

Mapping Structure-Function Relationships in the Brain.

Mapping the structural and functional connectivity of the brain is a major focus of systems neuroscience research and will help to identify causally important changes in neural circuitry responsible for behavioral dysfunction. Several methods for examining brain activity in humans have been extended to rodent and monkey models in which molecular and genetic manipulations exist for linking to human disease. In this review, which is part of a special issue focused on bridging brain connectivity information across species and spatiotemporal scales, we address mapping brain activity and neural connectivity in rodents using optogenetics in conjunction with either functional magnetic resonance imaging or optical intrinsic signal imaging.

Altered hemodynamics contribute to local but not remote functional connectivity disruption due to glioma growth.

Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth.

Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity.

Recovery after stroke, a major cause of adult disability, is often unpredictable and incomplete. Behavioral recovery is associated with functional reorganization (remapping) in perilesional regions, suggesting that promoting this process might be an effective strategy to enhance recovery. However, the molecular mechanisms underlying remapping after brain injury and the consequences of its modulation are poorly understood.