Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), are implicit in causing obesity. Mutations that reduce BDNF and TrkB expression are associated with obesity in humans and mice. Recently, it was reported that Bdnf gene deletion in the neurons of the paraventricular hypothalamus (PVH) caused positive energy balance and severe obesity in the form of hyperphagia, impaired adaptive thermogenesis, and decreased energy expenditure. Thus, we hypothesize that activation of these neurons will have the opposite effect and provide an opportunity for long-lasting obesity treatment. To specifically activate BDNF-expressing PVH (PVHBDNF) neurons, we injected Cre-dependent adeno-associated virus (AAV) expressing the excitatory DREADD hM3Dq bilaterally into the PVH of Bdnf2A-Cre/+ knock-in mice and then administered clozapine-N-oxide (CNO). Using this technique, we demonstrated that acute activation of these neurons rapidly decreased normal nocturnal feeding and fasting-induc...

It has been shown that P3b is not a signature of perceptual awareness per se but is instead more closely associated with postperceptual processing ([Cohen et al., 2020][1]). Here, we seek to investigate whether human participants’ attentional states are different in the report and the no-report conditions. This difference in attentional states, if exists, may lead to degraded consciousness of the stimuli in the no-report condition, and it therefore remains unknown whether the disappearance of P3b is because of a lack of reportability or degraded consciousness. Results of our experiment 1 showed that participants did experience degraded contents of consciousness in the no-report condition. However, results of experiment 2 showed that the degraded contents of consciousness did not influence the amplitude of P3b. These findings strengthen the claim that P3b is not a signature of perceptual awareness but is associated with postperceptual processing. [1]: #ref-14

Cisplatin-induced ototoxicity can be partially attributed to excessive reactive oxygen species (ROS) production, and agmatine is well-known for the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit ROS production. Whether agmatine could be used to alleviate cisplatin-induced ototoxicity is investigated. Cisplatin-exposed House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants showed increased ROS production detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and decreased cell viability detected by Cell Counting Kit-8 (CCK-8) or Myosin 7a staining, which could be reversed by the agmatine pretreatment. Cisplatin intraperitoneally injected C57BL/6 mice demonstrated damaged auditory function as indicated by distortion products otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) assays, and trans-tympanically administrated agmatine in the left ears could partly prevent the auditory function loss. Mechanisticall...

The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g., cough, bronchospasm). Airway innervation is heterogeneous, and distinct afferent subsets have distinct functional responses. However, little is known of the innervation patterns of subsets within the lung. A neuroanatomical map is critical for understanding afferent activation under physiological and pathophysiological conditions. Here, we quantified the innervation of the mouse lung by vagal and dorsal root ganglion (DRG) sensory subsets defined by the expression of Pirt (all afferents), 5HT3 (vagal nodose afferents), Tac1 (tachykinergic afferents), and transient receptor potential vanilloid 1 channel (TRPV1; defensive/nociceptive afferents) using Cre-mediated reporter expression. We found that vagal afferents innervate almost all conducting airways and project into the alveolar region, whereas DRG afferents only innervate large airways. Of the two vagal ganglia, onl...

Cortical spreading depression (CSD) is a wave of pronounced depolarization of brain tissue accompanied by substantial shifts in ionic concentrations and cellular swelling. Here, we validate a computational framework for modeling electrical potentials, ionic movement, and cellular swelling in brain tissue during CSD. We consider different model variations representing wild-type (WT) or knock-out/knock-down mice and systematically compare the numerical results with reports from a selection of experimental studies. We find that the data for several CSD hallmarks obtained computationally, including wave propagation speed, direct current shift duration, peak in extracellular K+ concentration as well as a pronounced shrinkage of extracellular space (ECS) are well in line with what has previously been observed experimentally. Further, we assess how key model parameters including cellular diffusivity, structural ratios, membrane water and/or K+ permeabilities affect the set of CSD characteristics.

The perirhinal cortex (PER) and postrhinal cortex (POR) in the medial temporal lobe are commonly described as two distinct systems that process nonspatial and spatial information, respectively. Recent findings suggest that the two regions exhibit functional overlap when processing stimulus information, especially when associative responses are required in goal-directed behavior. However, we lack the neural correlates of this. In the current study, we recorded spiking activities for single units of the PER and POR as rats were required to choose a response associated with the identity of a visual object or scene stimulus. We found that similar proportions of cells fired selectively for either scene or object between the two regions. In the PER and POR, response-selective neurons showed higher contrast for different responses than stimulus-selective cells did for stimuli. More cells fired selectively for specific choice response in the POR than in the PER. The differential firing patterns of the PER and POR ...

The human sensorimotor system is sensitive to both limb-related prediction errors and task-related performance errors. Prediction error signals are believed to drive implicit refinements to motor plans. However, an understanding of the mechanisms that performance errors stimulate has remained unclear largely because their effects have not been probed in isolation from prediction errors. Diverging from past work, we induced performance errors independent of prediction errors by shifting the location of a reach target but keeping the intended and actual kinematic consequences of the motion matched. Our first two experiments revealed that rather than implicit learning, motor adjustments in response to performance errors reflect the use of deliberative, volitional strategies. Our third experiment revealed a potential dissociation of performance-error-driven strategies based on error size. Specifically, behavioral changes following large errors were consistent with goal-directed or model-based control, known to...

Overlap between events can lead to interference because of a trade-off between encoding the present event and retrieving the past event. Temporal context information, “when” something occurred, a defining feature of episodic memory, can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference is unclear. Here, by identifying brain states using scalp eEEG from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification anal...

To explore whether the thalamus participates in lexical status (word vs. nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep brain stimulation lead implantation during a visually cued word- and nonword-reading aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time-locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multi-unit spiking activity, occurring shortly before and predominantly time-locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization ...

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice of both sexes while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel: an unbiased, temporally-precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for underst...