Interoception, the sensation and perception of internal bodily states, should be conceptualized through specialized modalities like cardioception, pulmoception, gastroception, and uroception. This NeuroView emphasizes cardioception, exploring heart-brain interactions, cardiac reflexes, and their influence on mental states and behavior.

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered

Plasticity allows organisms to form lasting adaptive changes in neural structures in response to interactions with the environment. It serves both species-general functions and individualized skill acquisition. To better understand human plasticity, we need to strengthen the dialogue between human research and animal models. Therefore, we propose to (1) enhance the interpretability of macroscopic methods

Abnormalities in thalamocortical crosstalk can lead to neuropsychiatric disorders. Variants in CACNA1G, which encodes the α1G subunit of the thalamus-enriched T-type calcium channel, are associated with absence seizures, intellectual disability, and schizophrenia, but the cellular and circuit consequences of these genetic variants in humans remain unknown. Here, we developed a human assembloid model

Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development

Efficient musculoskeletal simulators and powerful learning algorithms provide computational tools to tackle the grand challenge of understanding biological motor control. Our winning solution for the inaugural NeurIPS MyoChallenge leverages an approach mirroring human skill learning. Using a novel curriculum learning approach, we trained a recurrent neural network to control a realistic model of the

Latent-cause inference is the process of identifying features of the environment that have caused an outcome. This problem is especially important in social settings where individuals may not make equal contributions to the outcomes they achieve together. Here, we designed a novel task in which participants inferred which of two characters was more likely to have been responsible for outcomes achieved

Visceral and somatic pain serve as protective mechanisms against external threats. Accumulated evidence has confirmed that the paraventricular hypothalamus (PVH) plays an important role in the perception of visceral and somatic pain, whereas the exact neural pathways and molecules distinguishing them remain unclear. Here, we report distinct neuronal ensembles within the PVH dedicated to processing

Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the cornu ammonis (CA) region and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events for supporting this offline process. SWRs have been studied extensively, but the contribution of DSs remains unclear. By combining triple-ensemble (DG-CA3-CA1)

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously

There has been a recent renewal of interest in the therapeutic potential of serotonergic psychedelics. Here, we uncover the essential role of ventral hippocampus (vHpc) GABAergic interneurons in the anxiolytic effect evoked by the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Integrating anatomical, pharmacological, and genetic approaches, we show that 5-HT2A receptors in the CA1/subiculum

Here, we tested the respective contributions of primate premotor and prefrontal cortex to support vocal behavior. We applied a model-based generalized linear model (GLM) analysis that better accounts for the inherent variance in natural, continuous behaviors to characterize the activity of neurons throughout the frontal cortex as freely moving marmosets engaged in conversational exchanges. While analyses

Feedback at the photoreceptor synapse is the first neuronal circuit computation in vision, which influences downstream activity patterns within the visual system. Yet, the identity of the feedback signal and the mechanism of synaptic transmission are still not well understood. Here, we combined perturbations of cell-type-specific genes of mouse horizontal cells with two-photon imaging of the result

A remaining challenge for genetically encoded voltage indicators (GEVIs) is the reliable detection of excitatory postsynaptic potentials (EPSPs). Here, we developed ASAP5 as a GEVI with enhanced activation kinetics and responsivity near resting membrane potentials for improved detection of both spiking and subthreshold activity. ASAP5 reported action potentials (APs) in vivo with higher signal-to-noise

Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression

The EU AI Act, the first comprehensive regulation of AI, came into effect in August. Here, we provide an overview of the provisions that apply to the field of neurotechnology with respect to research and development and neuroscience practice and discuss some implications for the future.

Dynamic gain control of aversive signals enables adaptive behavioral responses. Although the role of amygdalar circuits in aversive processing is well established, the neural pathway for amplifying aversion remains elusive. Here, we show that the brainstem circuit linking the interpeduncular nucleus (IPN) with the nucleus incertus (NI) amplifies aversion and promotes avoidant behaviors. IPN GABA neurons

Incentives tend to drive improvements in performance. But when incentives get too high, we can “choke under pressure” and underperform right when it matters most. What neural processes might lead to choking under pressure? We studied rhesus monkeys performing a challenging reaching task in which they underperformed when an unusually large “jackpot” reward was at stake, and we sought a neural mechanism

Piezo1 is a mechanically activated cation channel that converts mechanical force into diverse physiological processes. Owing to its large protein size of more than 2,500 amino acids and complex 38-transmembrane helix topology, how Piezo1 is post-translationally modified for regulating its in vivo mechanotransduction functions remains largely unexplored. Here, we show that PKA activation potentiates

Episodic memory is organized in both spatial and temporal contexts. The hippocampus is crucial for episodic memory and has been demonstrated to encode spatial and temporal information. However, how the representations of space and time interact in the hippocampal memory system is still unclear. Here, we recorded the activity of hippocampal CA1 neurons in mice in a variety of one-dimensional navigation

Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all

Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson’s disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103+/− and/or TAU368+/− transgenic

The omnigenic model posits that genetic risk for traits with complex heritability involves cumulative effects of peripheral genes on mechanistic “core genes,” suggesting that in a network of genes, those closer to clusters including core genes should have higher GWAS signals. In gene co-expression networks, we confirmed that GWAS signals accumulate in genes more connected to risk-enriched gene clusters

Neuronal activity-regulated gene expression plays a crucial role in sculpting neural circuits that underpin adaptive brain function. Transcriptional enhancers are now recognized as key components of gene regulation that orchestrate spatiotemporally precise patterns of gene transcription. We propose that the dynamics of enhancer activation uniquely position these genomic elements to finely tune activity-dependent

The blood-brain barrier (BBB) serves as a crucial vascular specialization, shielding and nourishing brain neurons and glia while impeding drug delivery. Here, we conducted single-cell mRNA sequencing of human cerebrovascular cells from 13 surgically resected glioma samples and adjacent normal brain tissue. The transcriptomes of 103,230 cells were mapped, including 57,324 endothelial cells (ECs) and

Expansion of an intronic (GGGGCC)n repeat within the C9ORF72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) (C9-FTD/ALS), characterized with aberrant repeat RNA foci and noncanonical translation-produced dipeptide repeat (DPR) protein inclusions. Here, we elucidate that the (GGGGCC)n repeat RNA co-localizes with nuclear speckles and

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45–82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented

To memorize a sequence, one must serially bind each item to its rank order. How the brain controls a given input to bind its associated order in sequence working memory (SWM) remains unexplored. Here, we investigated the neural representations underlying SWM control using electrophysiological recordings in the frontal cortex of macaque monkeys performing forward and backward SWM tasks. Separate and

Mentoring the next generation of neuroscientists from historically excluded backgrounds brings several challenges. Successful mentor-mentee relationships are critical for addressing these challenges. Rodriguez-Romaguera and Quirk reflect on lessons learned from their cross-racial mentor-mentee relationship that could apply to many mentors.

In this issue of Neuron, Chen et al.1 found that lateral septum Esr1-expressing cells respond to both non-drug and drug rewards. Mice will lever press for optogenetic stimulation of these neurons, which are also critical to methamphetamine locomotor sensitization, conditioned place preference, self-administration, and reinstatement.

Precisely tracking time over second-long timescales is important for accurate anticipation and consequential actions, yet the neurobiological underpinnings remain unknown. In this issue of Neuron, Garcia-Garcia and colleagues1 show that computations in the cerebellum resulting from interactions between the mossy fiber and climbing fiber pathways contribute to long-interval learning during operant conditioning

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion’s direct ramifications within hours

Astrocytes are morphologically complex cells that serve essential roles. They are widely implicated in central nervous system (CNS) disorders, with changes in astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive and anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced morphology

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic

Spliceosomal GTPase elongation factor Tu GTP binding domain containing 2 (EFTUD2) is a causative gene for mandibulofacial dysostosis with microcephaly (MFDM) syndrome comprising cerebellar hypoplasia and motor dysfunction. How EFTUD2 deficiency contributes to these symptoms remains elusive. Here, we demonstrate that specific ablation of Eftud2 in cerebellar Purkinje cells (PCs) in mice results in severe

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain’s most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial

The role of experience in the organization of cortical feedback (FB) remains unknown. We measured the effects of manipulating visual experience on the retinotopic specificity of supragranular and infragranular projections from the lateromedial (LM) visual area to layer (L)1 of the mouse primary visual cortex (V1). LM inputs were, on average, retinotopically matched with V1 neurons in normally and dark-reared

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing

Pacinian corpuscle neurons are specialized low-threshold mechanoreceptors (LTMRs) that are tuned to detect high-frequency vibration (∼50–2,000 Hz); however, it is unclear how Pacinians and other LTMRs encode mechanical forces encountered during naturalistic behavior. Here, we developed methods to record LTMRs in awake, freely moving mice. We find that Pacinians, but not other LTMRs, encode subtle vibrations

In mammals, action potentials fired by rapidly adapting mechanosensitive afferents are known to reliably time lock to the cycles of a vibration. How and where along the ascending neuraxis is the peripheral afferent temporal code transformed into a rate code are currently not clear. Here, we probed the encoding of vibrotactile stimuli with electrophysiological recordings along major stages of the ascending

Human brain ontogeny is characterized by a considerably prolonged neotenic development of cortical neurons and circuits. Neoteny is thought to be essential for the acquisition of advanced cognitive functions, which are typically altered in intellectual disability (ID) and autism spectrum disorders (ASDs). Human neuronal neoteny could be disrupted in some forms of ID and/or ASDs, but this has never

Effective communication hinges on a mutual understanding of word meaning in different contexts. We recorded brain activity using electrocorticography during spontaneous, face-to-face conversations in five pairs of epilepsy patients. We developed a model-based coupling framework that aligns brain activity in both speaker and listener to a shared embedding space from a large language model (LLM). The

Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD’s interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor

The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC “inclusionopathy” models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like

Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent

Microglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson’s and Alzheimer’s disease, toxic aggregates of alpha-synuclein

Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological and psychiatric conditions, tuning NMDAR synaptic trapping to assess its clinical relevance for the treatment of brain conditions remains a challenge

Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here

Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal