Hydroxychloroquine (HCQ), a well-known antimalarial and anti-inflammatory drug, has demonstrated potential neuroprotective effects in ischemic stroke by inhibiting pyroptosis, a programmed cell death associated with inflammation. This study investigates the impact of HCQ on ischemic stroke pathology using both in vivo and in vitro models. In vivo, C57BL/6 mice subjected to middle cerebral artery occlusion (MCAO) were treated with HCQ. Neurological deficits, infarct volume, and the expression of pyroptosis markers were evaluated. The results demonstrated that HCQ significantly improved motor function and reduced infarct volume in the MCAO mouse model. In vitro, BV2 microglial cells exposed to lipopolysaccharide (LPS) and oxygen–glucose deprivation (OGD) were treated with HCQ. Western blot and immunofluorescence analyses revealed that HCQ effectively suppressed the expression of pyroptosis markers GSDMD and NLRP3 in both in vivo and in vitro models. These findings suggest that HCQ mitigates ischemic stroke d...

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub—a unique social operant chamber. PeerPub employs touch sensors to track the licking behavior on drinking spouts. When the number of licks meets a set reinforcement schedule, it dispenses a drop of solution with a fixed volume as a reward at the tip of the spout. A radio frequency identification (RFID) chip implanted in each rat’s skull identifies it throughout the experiment. The system is managed by a Raspberry Pi computer. We evaluated PeerPub using Sprague Dawley rats in daily 1 h sessions, where supersac (a glucose and saccharin solution) was provided under a fixed-ratio five schedule. We discovered that male rats consumed more supersac in dual rat conditions compared with single rat conditions. These findings illustrate PeerPub’s effectiveness in modeling the int...

The study of the neural circuitry underlying complex mammalian decision-making, particularly cognitive flexibility, is critical for understanding psychiatric disorders. To test cognitive flexibility, as well as potentially other decision-making paradigms involving multimodal sensory perception, we developed FlexRig, an open-source, modular behavioral platform for use in head-fixed mice. FlexRig enables the administration of tasks relying upon olfactory, somatosensory, and/or auditory cues and employing left and right licking as a behavior readout and reward delivery mechanism. The platform includes hardware and software components that are customizable, scalable, and portable, supporting a variety of behavioral assays. Using FlexRig, we established a head-fixed task to model attentional set-shifting, offering a new tool for neuroscience research that enhances the capacity for investigation of cognitive processes and their neural substrates, with broad applications in translational neuroscience.

Human face categorization has been extensively studied using event-related potentials (ERPs), positing the N170 ERP component as a robust neural marker of face categorization. Recently, the fast periodic visual stimulation (FPVS) approach relying on steady-state visual evoked potentials (SSVEPs) has also been used to investigate face categorization. FPVS studies consistently report strong bilateral SSVEP face categorization responses over the occipitotemporal cortex, with a right hemispheric dominance, closely mirroring the N170 scalp topography. However, it remains unclear whether SSVEP responses can be considered a proxy for the N170 or are driven by different components. To address this question, we recorded electrophysiological signals from observers viewing face and object images during FPVS and ERP paradigms. We quantified the FPVS response in the frequency domain and extracted ERP components, including the P1, N170, and P2, from both the FPVS time domain and ERP paradigms. Our results revealed littl...

Visual information emerging from the extrafoveal locations is important for visual search, saccadic eye movement control, and spatial attention allocation. Our everyday sensory experience with visual object categories varies across different parts of the visual field which may result in location-contingent variations in visual object recognition. We used a body, animal body, and chair two-forced choice object category recognition task to investigate this possibility. Animal body and chair images with various levels of visual ambiguity were presented at the fovea and different extrafoveal locations across the vertical and horizontal meridians. We found heterogeneous body and chair category recognition across the visual field. Specifically, while the recognition performance of the body and chair presented at the fovea were similar, it varied across different extrafoveal locations. The largest difference was observed when the body and chair images were presented at the lower-left and upper-right visual fields...

Psychiatric disorders, including anxiety and depression, are highly comorbid in people with epilepsy. However, the mechanisms mediating the shared pathophysiology are currently unknown. There is considerable evidence implicating the basolateral amygdala (BLA) in the network communication of anxiety and fear, a process demonstrated to involve parvalbumin-positive (PV) interneurons. The loss of PV interneurons has been well described in the hippocampus of chronically epileptic mice and in postmortem human tissue of patients with temporal lobe epilepsy (TLE). We hypothesize that a loss of PV interneurons in the BLA may contribute to comorbid mood disorders in epilepsy. To test this hypothesis, we employed a ventral intrahippocampal kainic acid model of TLE in mice, which exhibits profound behavioral deficits associated with chronic epilepsy. We demonstrate a loss of PV interneurons and dysfunction of the remaining PV interneurons in the BLA of chronically epileptic mice. Furthermore, we demonstrate altered pr...

Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) are known to contribute to both protective and pronociceptive processes. However, their contribution to neuropathic pain after spinal cord injury (SCI) needs further investigation. In a recent study utilizing TrkBF616A mice, it was shown that systemic pharmacogenetic inhibition of TrkB signaling with 1NM-PP1 (1NMP) immediately after SCI delayed the onset of pain hypersensitivity, implicating maladaptive TrkB signaling in pain after SCI. To examine potential neural mechanisms underlying the behavioral outcome, patch-clamp recording was performed in small-diameter dissociated thoracic (T) dorsal root ganglia (DRG) neurons to evaluate TrkB signaling in uninjured mice and after T10 contusion SCI. Bath-applied 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, induced a robust inward current in neurons from uninjured mice, which was attenuated by 1NMP treatment. SCI also decreased 7,8-DHF-induced current while increasing th...

Fragile X autosomal homolog 1 (FXR1), a member of the fragile X messenger riboprotein 1 family, has been linked to psychiatric disorders including autism and schizophrenia. Parvalbumin (PV) interneurons play critical roles in cortical processing and have been implicated in FXR1-linked mental illnesses. Targeted deletion of FXR1 from PV interneurons in mice has been shown to alter cortical excitability and elicit schizophrenia-like behavior. This indicates that FXR1 regulates behaviorally relevant electrophysiological functions in PV interneurons. We therefore expressed a genetically encoded hybrid voltage sensor in PV interneurons and used voltage imaging in slices of mouse somatosensory cortex to assess the impact of targeted FXR1 deletion. These experiments showed that PV interneurons lacking FXR1 had excitatory synaptic potentials with larger amplitudes and shorter latencies compared with wild type. Synaptic potential rise-times, decay-times, and half-widths were also impacted to degrees that varied bet...

The subjective visual vertical (VV), the visually estimated direction of gravity, is essential for assessing vestibular function and visuospatial cognition. In this study, we aimed to investigate the mechanisms underlying altered VV perception in stroke participants with unilateral spatial neglect (USN), specifically by examining their eye movement patterns during VV judgment tasks. Participants with USN demonstrated limited eye movement scanning along a rotating bar, often fixating on prominent ends, such as the top or bottom. This suggests a reflexive response to visually salient areas, potentially interfering with accurate VV perception. In contrast, participants without USN showed broader scanning around the center of the bar. Notably, participants with USN without frontal lobe lesions occasionally exhibited extended scanning that included the bar’s center, which was associated with accurate VV judgments. These findings suggest that (1) a tendency to fixate on peripheral, prominent areas and (2) fronta...

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Using in vivo calcium imaging in mice, we observed that AHA neuronal activity increases during footshock delivery and footshock-associated auditory cues. We found that following shock-induced increases in AHA activity, a decrease in activity coincides with the onset of grooming behavior. Next, we optogenetically activated the projections from the ventromedial hypothalamus (VMH) to the AHA and observed that photoactivation of the VMH→AHA pathway drives avoidance. Interestingly, repetitive grooming behavior occurs following cessation of stimulation. To identify changes in brain-wide activity patterns that occur due to optogenetic VMH→AHA stimulation, we combined optogenetic stimulation with positron emission tomography (PET)-based metabolic mapping. This approach revealed the amygdala as a downstream area activated by the stimulation of this pathway. Our findings show that the rise and fall of AHA neuronal activ...