The growing field of social neuroscience is reliant on the development of robust, ecologically valid paradigms for simulating social interaction and measuring social cognition in highly controlled laboratory settings. Perspective taking is a key component of social cognition, and accordingly several paradigms aimed at measuring perspective taking exist. A relatively novel paradigm is the ball detection task, in which participants and a virtual agent form independent beliefs about the presence of a target stimulus behind an occluder. Previous studies have shown that incongruent trials (in which the participant's and the agent's beliefs differ) affect participant reaction times and elicit increased neural activity in the so-called mentalizing network. This paradigm has important advantages over previous ones, in that experimental conditions can be fully randomized, and ceiling effects are not found even for adult populations. Here, we combined this paradigm with a stress induction and a nonstressful control ...

Each olfactory cortical hemisphere receives ipsilateral odor information directly from the olfactory bulb and contralateral information indirectly from the other cortical hemisphere. Since neural projections to the olfactory cortex (OC) are disordered and nontopographic, spatial information cannot be used to align projections from the two sides like in the visual cortex. Therefore, how bilateral information is integrated in individual cortical neurons is unknown. We have found, in mice, that the odor responses of individual neurons to selective stimulation of each of the two nostrils are significantly correlated, such that odor identity decoding optimized with information arriving from one nostril transfers very well to the other side. Nevertheless, these aligned responses are asymmetric enough to allow decoding of stimulus laterality. Computational analysis shows that such matched odor tuning is incompatible with purely random connections but is explained readily by Hebbian plasticity structuring bilatera...

The neural network, including the interstitial nucleus of Cajal (INC), functions as an oculomotor neural integrator involved in the control of vertical gaze holding. Impairment of the vestibulocerebellum (VC), including the flocculus (FL), has been shown to affect vertical gaze holding, indicating that the INC cooperates with the VC in controlling this function. However, a network between the INC and VC has not been identified. In this study, we aimed to obtain anatomical evidence of a neural pathway from the INC to the VC (the INC-VC pathway) in rats. Injection of dextran-conjugated Alexa Fluor 488 or adeno-associated virus 2-retro (AAV2retro) expressing GFP into the FL or another VC region (uvula/nodulus) did not reveal any retrogradely labeled neurons in the INC, suggesting that INC neurons do not project directly to the VC. Rabies virus-based transsynaptic tracing experiments revealed that the INC-VC pathway is mediated via synaptic connections with the prepositus hypoglossi nucleus (PHN) and medial ve...

Adeno-associated viral vector (AAV) serotypes vary in how effectively they express genes across different cell types and brain regions. Here we report a systematic comparison of the AAV serotypes 1, 2, 5, 8, 9, and the directed evolution derived AAVrg, in the inferior colliculus (IC) and cerebellum. The AAVs were identical apart from their different serotypes, each having a synapsin promotor and expressing GFP (AAV-hSyn-GFP). Identical titers and volumes were injected into the IC and cerebellum of adult male and female mice, and brains were sectioned and imaged 2 weeks later. Transduction efficacy, anterograde labeling of axonal projections, and retrograde labeling of somata were characterized and compared across serotypes. Cell-type tropism was assessed by analyzing the morphology of the GFP-labeled neurons in the cerebellar cortex. In both the cerebellum and IC, AAV1 expressed GFP in more cells, labeled a larger volume, and produced significantly brighter labeling than all other serotypes, indicating sup...

Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuroimmune cell signaling, but their roles in specific behavioral responses are not fully elucidated. Voltage-gated CaV2.2 channel activity in skin controls rapid and transient heat hypersensitivity induced by intradermal (i.d.) capsaicin via IL-1ɑ cytokine signaling. CaV2.2 channels are not, however, involved in mechanical hypersensitivity that developed in the i.d. capsaicin animal model. Here, we show that CaV2.2 channels are also critical for heat hypersensitivity induced by i.d. complete Freund adjuvant (CFA). i.d. CFA, a model of chronic neuroinflammation, involves ongoing cytokine signaling for days leading to pronounced edema and hypersensitivity to sensory stimuli. Peripheral CaV2.2 channel activity in the skin was required for the full development and week-long time course of heat hypersensitivity induced by i.d. CFA, but paw edema and me...

Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)–exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Fu...

Social status and dominance are critical factors influencing well-being and survival across multiple species. However, dominance behaviors vary widely across species, from elaborate feather displays in birds to aggression in chimps. To effectively study dominance, it is essential to clearly define and reliably measure dominance behaviors. In laboratory settings, C57BL/6 mice are commonly used to study dominance due to their stable and linear social hierarchies. However, other mouse strains are also used for laboratory research. Despite substantial evidence for strain effects on behavioral repertoires, the impact of strain on dominance in mice remains largely unstudied. To address this gap, we compared dominance behaviors between CD1 and C57BL/6 male mice across four assays: observation of agonistic behaviors, urine marking, tube test, and a reward competition. We found that CD1 mice demonstrate increased fighting, increased territorial marking through urination, and increased pushing and resisting in the t...

Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 ( N  = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, p NT). In Experiment 2 ( N  = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported “remembered” in nontarget responses) or informed guessing trials (participants self...

Successful behavior depends on the attentional state and other factors related to decision-making, which may modulate neuronal activity differently. Here, we investigated whether attentional state and behavioral outcome (i.e., whether a target is detected or missed) are distinguishable using the power and phase of local field potential recorded bilaterally from area V4 of two male rhesus monkeys performing a cued visual attention task. To link each trial's outcome to pairwise measures of attention that are typically averaged across trials, we used several methods to obtain single-trial estimates of spike count correlation and phase consistency. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase in attentional/behavioral discriminability, although single-trial gamma phase consistency provided reasonably high attentional discrimi...

Traditional microscopy techniques are limiting in that most only reflect two dimensions of a three-dimensional biological system.