Central sensitization plays a critical role in bladder pain syndrome/interstitial cystitis (BPS/IC). Electroacupuncture (EA) nerve stimulation therapy has been broadly acknowledged as an effective means of alleviating chronic pathological pain. However, it remains to be explored whether EA is effective in mitigating pain-sensitive symptoms of BPS/IC and the mechanisms involved. This study aims to investigate the analgesic effect and mechanism of EA therapy. We employed several techniques: mechanical pain threshold tests to assess pain sensitivity, urodynamic studies to evaluate bladder function, western blotting for protein analysis, immunofluorescence for visualizing, and transcriptomics. A rat cystitis model was established through a systemic intraperitoneal injection with cyclophosphamide (CYP). EA therapy was executed by stimulating the deep part of the hypochondriac point. EA treatment was observed to effectively reduce mechanical allodynia, enhance urinary function, suppress the activation of microgl...

Motor skill learning enables organisms to interact effectively with their environment, relying on neural mechanisms that integrate sensory feedback with motor output. While sensory feedback, such as auditory cues linked to motor actions, enhances motor performance in humans, its mechanism of action is poorly understood. Developing a reliable animal model of augmented motor skill learning is crucial to begin dissecting the biological systems that underpin this enhancement. We hypothesized that continuous auditory feedback during a motor task would promote complex motor skill acquisition in mice. We developed a closed-loop system using DeepLabCut for real-time markerless tracking of mouse forepaw movements with high processing speed and low latency. By encoding forepaw movements into auditory tones of different frequencies, mice received continuous auditory feedback during a reaching task requiring vertical displacement of the left forepaw to a target. Adult mice were trained over 4 d with either auditory fe...

Anterior–posterior interactions in the alpha band (8–12 Hz) have been implicated in various functions including perception, attention, and working memory. The underlying neural communication can be flexibly controlled by adjusting phase relations when activities across anterior–posterior regions oscillate at a matched frequency. We thus investigated how alpha oscillation frequencies spontaneously converged along anterior–posterior regions by tracking oscillatory EEG activity while participants rested. As more anterior–posterior regions (scalp sites) frequency-converged, the probability of additional regions joining the frequency convergence increased, and so did oscillatory synchronization (i.e., oscillatory power) at participating regions, suggesting that anterior–posterior frequency convergences are driven by inter-regional entrainment. Notably, frequency convergences were accompanied by two types of approximately linear phase gradients, one progressively phase lagged in the anterior direction, the poste...

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 8–12% of children globally. Hyperactivity-related behaviors, as well as inattention and impulsivity, are regarded as the nuclear symptoms of ADHD. At present, its etiologies and risk factors are unknown. Previous research linked TARP γ-8 deficiency to ADHD-like behaviors in mice, including hyperactivity, impulsivity, and memory deficits. Aniracetam, a nootropic drug, enhances cognition by modulating cholinergic activity and glutamate receptors, offering neuroprotective effects. This study examined TARP γ-8 knockout (KO) mice at 4 and 8 weeks, assessing behaviors through locomotor activity, cliff avoidance, novel object recognition, and contextual fear conditioning tests. TARP γ-8 KO mice exhibited hyperactivity, reduced recognition memory, and impaired short-term memory and long-term memory. Aniracetam administration improved these behavioral deficits, suggesting its potential as a therapeutic agent for ADHD. The ...

Neurons adapt to chronic activity changes by modifying synaptic properties, including neurotransmitter release. However, whether neuropeptide release via dense core vesicles (DCVs)—a distinct regulated secretory pathway—undergoes similar adaptation remains unclear. Here, we demonstrate that 24 h action potential blockade leads to significant DCV accumulation in primary mouse cortical neurons of both sexes. Reactivation with action potential trains induced enhanced Ca2+ influx and 700% more DCV exocytosis compared with control neurons. Notably, total DCV cargo protein levels were unchanged, while mRNA levels of corresponding genes were reduced. Blocking neurotransmitter release with Tetanus toxin induced DCV accumulation, similar to that induced by network silencing with TTX. Hence, chronic network silencing triggers increased DCV accumulation due to reduced exocytosis during silencing. These accumulated DCVs can be released upon reactivation resulting in a massive potentiation of DCV exocytosis, possibly c...

Cutaneomuscular reflexes (CMRs) can be recorded in the hand muscle of human subjects after stimulation of a digital nerve. We hypothesized that repeated synchronous stimulation of nerves from two digits may lead to long-term plastic changes in CMR, by the mechanisms of spike-timing–dependent plasticity (STDP). To test this idea, we conducted experiments in 27 healthy human volunteers. After baseline measurement of CMR, one of four 30-min-long stimulation conditions were tested; the CMR was then remeasured. The four conditions were simultaneous index finger and thumb stimulation; asynchronous index finger and thumb stimulation; thumb 5 ms before index finger stimulation; and thumb-only stimulation. Neither the early (E1) nor late excitatory (E2) components of the CMR showed consistent changes after any stimulation condition. The inhibitory (I1) component was slightly reduced in all cases. To understand why paired stimulation did not produce long-term changes, we conducted a further experiment. In this, we m...

Mitral cells (MCs) and tufted cells (TCs) in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly arranged MCs with a diameter larger than 20 µm in the mitral layer (ML) and smaller TCs spread across both the ML and external plexiform layers (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch–clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in vivo and ex vivo data and test a soma size-based classifier of bulbar projection neurons using passive and intrinsic firing properties. We found that the...

Beta event-related spectral perturbation, including bilateral movement-related beta desynchronization (MRBD) and postmovement beta synchronization (PMBS), can be evoked by unilateral speed movement. A potential correlation might exist between power (de)synchronization and interhemispheric coherence during movement execution. However, during the PMBS phase, the existence of interhemispheric coupling and the effect of speed on it are largely undiscovered. To answer this question, we investigated eight healthy, right-handed volunteers using a combination of electroencephalography, transcranial magnetic stimulation, and electromyography. We explored interhemispheric (directed) coherence during isotonic right index finger abduction movements at two speeds: ballistic and self-paced. We discovered that (1) interhemispheric coherence was greater during the PMBS than during the MRBD period. Furthermore, ballistic movement induced a larger coherence during the PMBS period, but not during the MRBD period. (2) In the ...

Stress is a common occurrence for military personnel. This can include the stress of deployment and active combat. Anxiety is considered a reaction to stress, and with anxiety-related disorders on the rise, it is imperative that stress be considered a preexisting condition when studying a number of neurological conditions. To determine the effects of stress on the behavioral outcomes of traumatic brain injury (TBI), we used a 3 d acute unpredictable stress (AUS) model followed by blast-induced neurotrauma (BINT) to assess social anhedonia and anxiety-like behaviors in male and female rats. The animals were divided into four groups including unstressed and uninjured control (Con), stress-only animals (AUS), injury-only animals (BINT), and animals that received both stress and injury (AUS + BINT). In the males, behavioral tests such as elevated plus and three-chamber sociability (3-CS) showed that stress plays a dominant role in determining behavioral outcomes after TBI with the AUS + BINT animals behaving m...

We aimed to better understand the dynamics of cortical neurons during nonREM sleep—a state in which neuronal populations are silenced for ∼100 ms of every second due to delta wave fluctuations. This alternation between periods of population spiking (“UP states”) and silence (“DOWN states”) generally synchronizes populations at the 1 s timescale, although some prior work has shown that anticorrelations in nonREM can occur in pairs of neurons that are anticorrelated in wake. We used 24 h recordings of frontal cortical neurons in rats to measure cross-correlation between pairs of neurons in wake, nonREM, and REM. Surprisingly, while most pairs of neurons were synchronized, we found a minority of pairs that showed significant nonREM-induced desynchronization, as indicated by negative cross-correlations in nonREM without equivalent anticorrelation in wake or REM. Interestingly, the degree of anticorrelation within NREM epochs was positively modulated by oscillations in the low-frequency (i.e., “delta” or 1–4 Hz...