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...

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...

Mammalian parenting is an unusually demanding commitment. How has the reward system been co-opted to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient primiparous mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams toward their biological pups. Next, we demonstrate that chronic chemogenetic inactivation of the LHb using inhibitory DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercept model suggesting LHb inactivation prevents the acquisition of pup retrieval, a novel maternal behavior in primiparous mouse dams, and decreases nest building performance, an already-established behavior, in primiparous mouse dams. Lastly, we examine the spatial histology of kainic acid-tre...

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...

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...

Status epilepticus (SE) links to high mortality and morbidity. Considering the neuroprotective property of baicalein (BA), we investigated its effects on post-SE neuronal injury via the NLRP3/GSDMD pathway. Mice were subjected to SE modeling and BA interference, with seizure severity and learning and memory abilities evaluated. The histological changes, neurological injury and neuron-specific enolase (NSE)-positive cell number in hippocampal CA1 region, and cell death were assessed. Levels of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3)/gasdermin-D (GSDMD) pathway-related proteins, inflammatory factors, and Iba-1 + NLRP3+ and Iba-1 + GSDMD-N+ cells were determined. BA ameliorated post-SE cognitive dysfunction and neuronal injury in mice, as evidenced by shortened escape latency, increased number of crossing the target quadrant within 60 s and the time staying in the target quadrant, alleviated hippocampal damage, increased viable cell number, decreased neuronal injury, and increased NSE-positive c...

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.

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...

In the article “Short-Term Synaptic Plasticity Makes Neurons Sensitive to the Distribution of Presynaptic Population Firing Rates,” by Luiz Tauffer and Arvind Kumar, which was published online …

Short-term motor adaptation to novel movement dynamics has been shown to involve at least two concurrent learning processes: a slow process that responds weakly to error but retains information well and a fast process that responds strongly to error but has poor retention. This modeling framework can explain several properties of motion-dependent motor adaptation (e.g., 24 h retention). An important assumption of this computational framework is that learning is only based on the experienced movement error, and the effect of noise (either internally generated or externally applied) is not considered. We examined the respective error sensitivity by quantifying adaptation in three subject groups distinguished by the noise added to the motion-dependent perturbation. We assessed the feedforward adaptive changes in motor output and examined the adaptation rate, retention, and decay of learning. Applying a two-state modeling framework showed that the applied noise during training mainly affected the fast learning...