Protocadherins, a family of adhesion molecules with crucial role in cell-cell interactions, have emerged as key players in neurodevelopmental and psychiatric disorders. In particular, growing evidence links genetic alterations in Protocadherin 9 (PCDH9) gene with Autism Spectrum Disorder (ASD) and Major Depressive Disorder (MDD). Furthermore, Pcdh9 deletion induces neuronal defects in the mouse somatosensory

A key challenge in understanding the functional organisation of visual cortex stems from the fact that only a small proportion of the objects experienced during natural viewing can be presented in a typical experiment. This constraint often leads to experimental designs that compare responses to objects from experimenter-defined stimulus conditions, potentially limiting the interpretation of the data

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal

Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics

Cognitive models of reading assume that speech production occurs after visual and phonological processing of written words. This traditional view is at odds with more recent magnetoencephalography studies showing that the left posterior inferior frontal cortex (pIFC) classically associated with spoken production responds to print at 100-150 ms after word-onset, almost simultaneously with posterior

Understanding how heterogeneous neural populations represent sensory input to give rise to behavior remains a central problem in systems neuroscience. Here we investigated how midbrain neurons within the electrosensory system of Apteronotus leptorhynchus code for object location in space. In vivo simultaneous recordings were achieved via Neuropixels probes, high-density electrode arrays, with the stimulus

Predictive processing in parietal, temporal, frontal, and sensory cortex allows us to anticipate future meanings to maximize the efficiency of language comprehension, with the temporoparietal junction (TPJ) and inferior frontal gyrus (IFG) thought to be situated towards the top of a predictive hierarchy. Although the regions underpinning this fundamental brain function are well-documented, it remains

Retinal ganglion cells (RGCs) are the neuronal connections between the eye and the brain conveying multiple features of the outside world through parallel pathways. While there is a large body of literature how these pathways arise in the retinal network, the process of converting presynaptic inputs into RGC spiking output is little understood. In this study, we show substantial differences in the

Human visual cortex contains regions selectively involved in perceiving and recognizing ecologically important visual stimuli such as people and places. Located in the ventral temporal lobe, these regions are organized consistently relative to cortical folding, a phenomenon thought to be inherited from how centrally or peripherally these stimuli are viewed with the retina. While this eccentricity theory

Key event-related potentials (ERPs) of perceptual decision-making such as centroparietal positivity (CPP) elucidate how evidence is accumulated toward a given choice. Furthermore, this accumulation can be impacted by visual target selection signals such as the N2 contralateral (N2c). How these underlying neural mechanisms of perceptual decision-making are influenced by the spatial congruence of distractors

Plasticity in the subcortical motor basal ganglia–thalamo–cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information

Systemic study of pathogenic pathways and interrelationships underlying genes associated with Alzheimer's disease (AD) facilitates the identification of new targets for effective treatments. Recently available large-scale multiomics datasets provide opportunities to use computational approaches for such studies. Here, we devised a novel disease gene identification (digID) computational framework that

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (Ih), or by genetic deletion of HCN1. GABAergic

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy

Different people listening to the same story may converge upon a largely shared interpretation while still developing idiosyncratic experiences atop that shared foundation. What linguistic properties support this individualized experience of natural language? Here, we investigate how the "concrete–abstract" axis—the extent to which a word is grounded in sensory experience—relates to within- and across-subject

The precise regulation of Ca2+ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca2+ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca2+ spikes generated by Kv2.1-organized Ca2+ microdomains. Furthermore, glucocorticoids

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific

The external segment of the globus pallidus (GPe) is involved in the modulation of motor output and limbic components of behavior. The circuitry by which the GPe contributes to limbic components of behavior remains unknown. While many investigations have focused on the local circuitry within the basal ganglia, numerous GPe projections to target regions outside of the basal ganglia including the midbrain

The debate on the neural basis of multitasking costs evolves around neural overlap between concurrently performed tasks. Recent evidence suggests that training-related reductions in representational overlap in fronto-parietal brain regions predict multitasking improvements. Cognitive theories assume that overlap of task representations may lead to unintended information exchange between tasks (i.e

Sensory experience and learning are thought to be associated with plasticity of neocortical circuits. Repetitive sensory stimulation can induce long-term potentiation (LTP) of cortical excitatory synapses in anesthetized mice; however, it is unclear if these phenomena are associated with sustained changes in activity during wakefulness. Here we used time-lapse, calcium imaging of layer (L) 2/3 neurons

The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO2, depends on interactions between respiratory chemoreflexes and arousal state. The ventilatory response to CO2 is triggered by neurons in the retrotrapezoid nucleus (RTN) that function as sensors of central pH, which can be identified in adulthood by expression of Phox2b and Neuromedin B. Here we examine the dynamic response

Obsessive-Compulsive Disorder (OCD) is a debilitating illness consisting of obsessions and compulsions. OCD severity and treatment response are correlated with avoidant behaviors thought be performed to alleviate obsession-related anxiety. However, little is known about either the role of avoidance in the development of OCD or the interplay between anxiety states and avoidance behaviors. We have developed

The gonadotropin-releasing hormone (GnRH) neurons operate as a neuronal ensemble exhibiting coordinated activity once every reproductive cycle to generate the preovulatory GnRH surge. Using GCaMP fibre photometry at the GnRH neuron distal dendrons to measure the output of this widely scattered population in female mice, we find that the onset, amplitude, and profile of GnRH neuron surge activity exhibits

The transmission of tau pathology has been proposed as one of the major mechanisms for the spatiotemporal spreading of tau pathology in neurodegenerative diseases. Over the last decade, studies have demonstrated that targeting total or pathological tau using tau antibodies can mitigate the development of tau pathology in tauopathy or Alzheimer's disease (AD) mouse models, and multiple tau immunotherapy

The interplay between attention, alertness and motor planning is crucial for our manual interactions. To investigate the neural bases of this interaction, and challenging the views that attention cannot be disentangled from motor planning, we instructed human volunteers of both sexes to plan and execute reaching movements while attending to the target, while attending elsewhere, or without constraining

Huntington's disease (HD) is a progressive neurodegenerative disorder with no cure, characterized by significant neurodegeneration of striatal GABAergic medium spiny neurons (MSNs). Early stages of the disease are characterized by the loss of dopamine 2 receptor-expressing MSNs (D2 MSNs) followed by degeneration of dopamine 1 receptor-expressing MSNs (D1 MSNs), leading to aberrant basal ganglia signaling

The mammalian cochlea amplifies sounds selectively to improve frequency resolution. However, vibrations around the outer hair cells (OHCs) are amplified non-selectively. The mechanism of the selective or non-selective amplification is unknown. This study demonstrates that active force transmission through the extracellular fluid in the organ of Corti (Corti fluid) can explain how the cochlea achieves

A previous epidemiological study in Northern Europe showed that the A673T mutation (Icelandic mutation) in the amyloid precursor protein gene (APP) can protect against Alzheimer's disease (AD). While the effect of the A673T mutation on APP processing has been investigated primarily in vitro, its in vivo impact has not been evaluated. This is mainly because most existing AD mouse models carry the Swedish

Mesenchymal stromal cell (MSC) therapy has regenerative potentials to treat various pathological conditions including neurological diseases. MSCs isolated from various organs can differentiate into specific cell types to repair organ damages. However, their paracrine mechanisms are predicted to predominantly mediate their immunomodulatory, pro-angiogenic, and regenerative properties. While preclinical

Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel technique for noninvasive brain stimulation (NIBS). TUS delivered in a theta (5 Hz) burst pattern (tbTUS) induces plasticity in the human primary motor cortex (M1) for 30–60 min, showing promise for therapeutic development. Metaplasticity refers to activity-dependent changes in neural functions governing synaptic plasticity;

GABAergic inhibitory interneurons comprise many subtypes that differ in their molecular, anatomical, and functional properties. In mouse visual cortex, they also differ in their modulation with an animal’s behavioral state, and this state modulation can be predicted from the first principal component (PC) of the gene expression matrix. Here, we ask whether this link between transcriptome and state-dependent

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular

The capabilities of the human ear are remarkable. We can normally detect acoustic stimuli down to a threshold sound-pressure level of 0 dB (decibels) at the entrance to the external ear, which elicits eardrum vibrations in the picometer range. From this threshold up to the onset of pain, 120 dB, our ears can encompass sounds that differ in power by a trillionfold. The comprehension of speech and enjoyment

Dopamine (DA) and norepinephrine (NE) have been repeatedly implicated in neuropsychiatric vulnerability, in part via their roles in mediating the decision-making processes. Although two neuromodulators share a synthesis pathway and are coactivated under states of arousal, they engage in distinct circuits and modulatory roles. However, the specific role of each neuromodulator in decision-making, in

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode

In demanding listening situations, a listener's motivational state may affect their cognitive investment. Here, we aim to delineate how domain-specific sensory processing, domain-general neural alpha power, and pupil size as a proxy for cognitive investment encode influences of motivational state under demanding listening. Participants (male and female) performed an auditory gap-detection task while

It is well established that holding information in working memory (WM) elicits sustained stimulus-specific patterns of neural activity. Nevertheless, here we provide evidence for a distinct class of neural activity that tracks the number of individuated items in working memory, independent of the type of visual features stored. We present two EEG studies of young adults of both sexes that provide robust

Harmonics are an integral part of music, speech, and vocalizations of animals. Since the rest of the auditory environment is primarily made up of nonharmonic sounds, the auditory system needs to perceptually separate the above two kinds of sounds. In mice, harmonics, generally with two-tone components (two-tone harmonic complexes, TTHCs), form an important component of vocal communication. Communication

Odor information arrives first in the main olfactory bulb and is then broadcasted to the olfactory cortices and striatum. Downstream regions have unique cellular and connectivity architectures that may generate different coding patterns to the same odors. To reveal region-specific response features, tuning and decoding of single-unit populations, we recorded responses to the same odors under the same

Aggression involves both sexually monomorphic and dimorphic actions. How the brain implements these two types of actions is poorly understood. We found that in Drosophila melanogaster, a set of neurons, which we call CL062, previously shown to mediate male aggression also mediate female aggression. These neurons elicit aggression acutely and without the presence of a target. Although the same set of

Intracranial potentials are used as functional biomarkers of neural networks. As potentials spread away from the source populations, they become mixed in the recordings. In humans, interindividual differences in the gyral architecture of the cortex pose an additional challenge, as functional areas vary in location and extent. We used source separation techniques to disentangle mixing potentials obtained

Cognitive control is engaged by working memory processes and high-demand situations like antisaccade, where one must suppress a prepotent response. While it is known to be supported by the frontoparietal control network, how intra- and inter-areal dynamics contribute to cognitive control processes remain unclear. N-Methyl-D-aspartate glutamate receptors (NMDARs) play a key role in prefrontal dynamics

Neonatal hypoxia (Hx) causes white matter (WM) injury, particularly in the cerebellum. We previously demonstrated Hx-induced reduction of cerebellar Purkinje cell (PC) activity results in locomotor deficits. Yet, the mechanism of Hx-induced cerebellar WM injury and associated locomotor abnormalities remains undetermined. Here, we show that the cerebellar WM injury and linked locomotor deficits are

Hostility often co-occurs in parents and associates with increased aggression and inattention problems in children. In this population-based cohort of 484 mother-father-child neuroimaging trios, we investigated the degree to which associations of prenatal and childhood parental hostility would be associated with maternal, paternal and child brain structural differences. Also, we examined whether hippocampal

Barn owls enable investigation of neural mechanisms underlying stimulus selection of concurrent stimuli. The audio-visual space map in the optic tectum (OT), avian homologue of the superior colliculus, encodes relative strength of concurrent auditory stimuli through spike response rate and interneuronal spike train synchrony (STS). Open questions remain regarding stimulus selection in downstream forebrain

From a young age, children have advanced social perceptual and reasoning abilities. However, the neural development of these abilities is still poorly understood. To address this gap, we used fMRI data collected 122 3-12-year-old children (64 females) and 33 adults (20 females) watched an engaging and socially rich movie to investigate how the cortical basis of social processing changes throughout

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing