Journal of neurophysiology
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The recent discovery of cyclic GMP-AMP synthase (cGAS) as the mammalian cytosolic DNA sensor has profound therapeutic implications for infection, immunology, and cancer. Because neurovirology, neuroimmunology, neuro-oncology, and neurodegeneration implicate cytosolic DNA sensing, cGAS activation and induction of the downstream signaling protein stimulator of interferon genes (STING) has become increasingly recognized as a crucial determinant of neuropathophysiology. This Neuro Forum article reviews recent advances on the role of cGAS-STING signaling in neuroinflammation and neurological disease.
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Electrophysiological and imaging studies from humans suggest that the phantom sound of tinnitus is associated with abnormal thalamocortical neural oscillations (dysrhythmia) and enhanced gamma band activity in the auditory cortex. However, these models have seldom been tested in animal models where it is possible to simultaneously assess the neural oscillatory activity within and between the thalamus and auditory cortex. To explore this issue, we used multichannel electrodes to examine the oscillatory behavior of local field potentials recorded in the rat medial geniculate body (MBG) and primary auditory cortex (A1) before and after administering a dose of sodium salicylate (SS) that reliably induces tinnitus. ⋯ Neural models of tinnitus suggest that it arises from abnormal thalamocortical oscillations, but these models have not been extensively tested. This article identifies abnormal thalamocortical oscillations in a drug-induced tinnitus model. Our findings open up new avenues of research to investigate whether cellular mechanisms underlying thalamocortical oscillations are causally linked to tinnitus.
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Task performance is determined not only by the amount of task-relevant signal present in our brains but also by the presence of noise, which can arise from multiple sources. Internal noise, or "trial variability," manifests as trial-by-trial variations in neural responses under seemingly identical conditions. External factors can also translate into noise, particularly when a task requires extraction of a particular type of information from our environment amid changes in other task-irrelevant "nuisance" parameters. ⋯ NEW & NOTEWORTHY Many everyday tasks require us to extract specific information from our environment while ignoring other things. When the neurons in our brains that carry task-relevant signals are also modulated by task-irrelevant "nuisance" information, nuisance modulation is expected to act as performance-limiting noise. Using both simulated and recorded neural data, we demonstrate that these intuitions are misguided when the brain operates in a fast-processing, low-spike-count regime, where nuisance variability is largely inconsequential for performance.
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Osteoarthritis (OA) is a debilitating conditioning with pain as the major clinical symptom. Understanding the mechanisms that drive OA-associated chronic pain is crucial for developing the most effective analgesics. Although the degradation of the joint is the initial trigger for the development of chronic pain, the discordance between radiographic joint damage and the reported pain experience in patients, coupled with clinical features that cannot be explained by purely peripheral mechanisms, suggest there are often other factors at play. ⋯ Furthermore, we suggest a compensatory increase in descending serotonergic inhibition acting at 5-HT7 receptors as the model progresses such that receptor activation is sufficient to override the imbalance in descending controls and mediate neuronal inhibition. NEW & NOTEWORTHY This study showed that there are both noradrenergic and serotonergic components contributing to the expression of diffuse noxious inhibitory controls (DNIC). Furthermore, although a tonic descending noradrenergic tone is always crucial for the expression of DNIC, variations in descending serotonergic signaling over the course of the model mean this component plays a more vital role in states of sensitization.
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General anesthesia is ubiquitous in research and medicine, yet although the molecular mechanisms of anesthetics are well characterized, their ultimate influence on cortical electrophysiology remains unclear. Moreover, the influence that different anesthetics have on sensory cortexes at neuronal and ensemble scales is mostly unknown and represents an important gap in knowledge that has widespread relevance for neural sciences. To address this knowledge gap, this work explored the effects of isoflurane and ketamine/xylazine, two widely used anesthetic paradigms, on electrophysiological behavior in mouse primary visual cortex. ⋯ NEW & NOTEWORTHY We directly compared electrophysiological responses in awake and anesthetized (isoflurane or ketamine) mice. We also proposed a method for quantifying and visualizing highly variable, evoked multiunit activity. Lastly, we observed distinct oscillatory responses to stimulus onset and offset in awake and isoflurane-anesthetized mice.