搜索结果：Frontiers in neural circuits

Noggin is a glycosylated protein that acts as an antagonist of bone morphogenetic proteins and has been implicated in astrogliosis and functional recovery after spinal cord injury (SCI). Although Noggin is known to regulate astrocytic responses, its role in reactive astrogliosis and glial scar formation after SCI remains unclear. Under normal conditions, Noggin is expressed in astrocytes in the white matter of the mouse spinal cord. In this study, we investigated the role of Noggin in reactive astrogliosis and glial scar formation after SCI. We first examined the expression pattern of Noggin in the mouse spinal cord after SCI. To assess the functional role of Noggin, we used Nestin-Cre; Nogginflox/flox conditional knockout mice, in which Noggin is conditionally deleted from astrocytes and neurons in the spinal cord. In addition, neutralizing anti-Noggin antibodies were continuously administered to the lesion site using micro-osmotic pumps. GFAP expression and motor function after SCI were then evaluated. As a result, we found that Noggin was upregulated in reactive astrocytes after SCI, suggesting its involvement in the injury response. Conditional deletion of Noggin markedly suppressed glial fibrillary acidic protein (GFAP) expression after SCI. Consistently, local administration of neutralizing anti-Noggin antibodies also reduced GFAP expression around the lesion site. However, anti-Noggin antibody treatment deteriorated motor function after SCI. These findings suggest that Noggin is an important regulator of reactive astrogliosis and contributes to glial scar formation after SCI. Although suppression of Noggin reduced GFAP expression and attenuated glial scar formation, it did not improve functional recovery. Rather, motor function was worsened, indicating that reduced glial scar formation may not necessarily be beneficial after SCI. Noggin-mediated astrogliosis may therefore play a protective role in the injured spinal cord.

Although the autonomic sympathetic system is activated in parallel with locomotion, the underlying neural mechanisms mediating this coordination are not completely understood. Descending exercise or "central command" signals from hypothalamic and brainstem regions are thought to activate thoracic spinal sympathetic neurons in parallel with descending locomotor commands. In turn, subsets of thoracic sympathetic preganglionic neurons (SPNs) increase activity in a constellation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. It is known that ascending drive from lumbar locomotor networks is mediated in part via propriospinal neurons that can also activate and coordinate autonomic systems. However, the extent to which this ascending drive is distributed to SPNs within thoracic regions is unknown. To investigate this, we applied neurochemicals to elicit whole-cord or lumbar-evoked locomotor activity in an in vitro spinal cord preparation, simultaneously recording lumbar ventral root (VR) activity and changes in normalized calcium fluorescence (Ca-RI) of pre-labelled SPNs in thoracic segments. Using whole-bath drug application SPN responses appeared unimodal, such that SPN Ca-RI was increased in rostral (T4-FT7) compared to caudal (T8-T11) segments during tonic activity. During rhythmic activity in either whole or split-bath configuration, and during tonic activity in split-bath configuration, SPN responses appeared trimodal, such that SPN Ca-RI was increased in mid-thoracic segments (T6-7) and reduced at more rostral (T4-5) and caudal (T8-9) levels. In both approaches, the greatest increases in SPNs Ca-RI during rhythmic activity were at T6-7, and most decreased at caudal segments (T8-T11). Together, these findings reveal a strong ascending lumbar to thoracic integrating communication pathway, which may represent a key feature of spinal neural network function normally. Such communication pathways should be further investigated for targeted autonomic function(s) activation and therapeutic benefit after spinal cord injury.

The 5-HT2C receptor is involved in the regulation of spinal motor function, specifically in both volitional and involuntary motor behavior. It contributes to various aspects of voluntary movement, such as locomotion, gait, coordination, and muscle contractions. It also contributes to involuntary motor behavior (i.e., spasms), which affects many individuals with spinal cord injury. Despite its known involvement in motor function, additional research in uninjured mice is required to assess whether specific gait parameters and muscle contractility are directly linked to the 5-HT2C receptor. In injured mice, further research is needed to determine whether the expression of the 5-HT2C receptor is altered in the lumbar and sacral spinal cord after injury. It is also necessary to determine whether voluntary locomotion, involuntary motor behavior, or the expression of this receptor is influenced by sex, as it is unknown if there is a difference in 5-HT2C receptor expression between male and female mice. The aim of this study is to investigate volitional and involuntary motor behavior of male and female uninjured and spinal cord-injured knock-out mice. Mice that express a non-functional form of the 5-HT2C receptor were compared to typical-functioning wildtype mice. Volitional behavioral assessments revealed mild strength and stability deficits in the knock-out mice when compared to wildtype mice. We also compared the capacity of spinal cord tissue to generate sensory evoked activity, and it was revealed that male knock-out mice exhibited less involuntary motor behavior both ex vivo and in vivo than male wildtype mice. Western blot analysis revealed that injury status, sex, and genotype affected the relative expression of the 5-HT2C receptor in both the lumbar and sacral spinal cord, with female KO mice exhibiting a compensatory mechanism post-SCI via upregulation of the 5-HT2A receptor. Through a comprehensive approach combining behavioral assessments, electrophysiological experiments, and whole-tissue protein analysis, our findings provide strong evidence that the 5-HT2C receptor is differentially regulated by sex, genotype, and spinal cord injury. These findings underscore the importance of considering sex as a biological variable and suggest that future therapeutic strategies targeting the 5-HT2C receptor account for sex-specific differences in 5-HT2C receptor expression and function.

The neural circuits of the striatum (caudate and putamen) constitute a crucial component of the extrapyramidal motor system, and dysfunction in these circuits is correlated with significant neurological disorders including Parkinson's disease and Huntington's disease. Many previous studies in rodents revealed the neural connections of the rostral and intermediate parts of the striatum, but relatively fewer studies focused on the caudal striatum, which likely contains both the tail of caudate (CaT) and caudal putamen (PuC). In this study, we investigate the gene markers for the CaT and PuC and brain-wide afferent and efferent projections of the caudal striatum in mice using both anterograde and retrograde neural tracing methods. Some genes such as prodynorphin, otoferlin, and Wolfram syndrome 1 homolog are strongly expressed in CaT and PuC while some others such as neurotensin are almost exclusively expressed in CaT. The major afferent projections of the CaT originate from the substantia nigra (SN), ventral tegmental area, basolateral amygdala, parafascicular nucleus, and visual, somatosensory, auditory and parietal association cortices. The PuC receives its main inputs from the posterior intralaminar nucleus, ventroposterior medial nucleus (VPM), medial geniculate nucleus, and entorhinal, motor and auditory cortices. Both CaT and PuC neurons (including dopamine receptor 1 expressing ones) project in a rough topographical manner to the external and internal divisions of globus pallidus (GP) and SN. However, dopamine receptor 2 expressing neurons in nearly all striatal regions (including CaT and PuC) exclusively target the external GP. In conclusion, the present study has identified the mouse equivalent of the primate CaT and revealed detailed brain-wide connections of the CaT and PuC in rodent. These findings would offer new insights into the functional correlation and disease-related neural circuits related to the caudal striatum.

Neurons throughout the neocortex exhibit selective sensitivity to particular features of sensory input patterns. According to the prevailing views, cortical strategy is to choose features that exhibit predictable relationship to their spatial and/or temporal context. Such contextually predictable features likely make explicit the causal factors operating in the environment and thus they are likely to have perceptual/behavioral utility. The known details of functional architecture of cortical columns suggest that cortical extraction of such features is a modular nonlinear operation, in which the input layer, layer 4, performs initial nonlinear input transform generating proto-features, followed by their linear integration into output features by the basal dendrites of pyramidal cells in the upper layers. Tuning of pyramidal cells to contextually predictable features is guided by the contextual inputs their apical dendrites receive from other cortical columns via long-range horizontal or feedback connections. Our implementation of this strategy in a model of prototypical V1 cortical column, trained on natural images, reveals the presence of a limited number of contextually predictable orthogonal basis features in the image patterns appearing in the column's receptive field. Upper-layer cells generate an overcomplete Hadamard-like representation of these basis features: i.e., each cell carries information about all basis features, but with each basis feature contributing either positively or negatively in the pattern unique to that cell. In tuning selectively to contextually predictable features, upper layers perform selective filtering of the information they receive from layer 4, emphasizing information about orderly aspects of the sensed environment and downplaying local, likely to be insignificant or distracting, information. Altogether, the upper-layer output preserves fine discrimination capabilities while acquiring novel higher-order categorization abilities to cluster together input patterns that are different but, in some way, environmentally related. We find that to be fully effective, our feature tuning operation requires collective participation of cells across 7 minicolumns, together making up a functionally defined 150 μm diameter "mesocolumn." Similarly to real V1 cortex, 80% of model upper-layer cells acquire complex-cell receptive field properties while 20% acquire simple-cell properties. Overall, the design of the model and its emergent properties are fully consistent with the known properties of cortical organization. Thus, in conclusion, our feature-extracting circuit might capture the core operation performed by cortical columns in their feedforward extraction of perceptually and behaviorally significant information.

Intraoperative intracranial electrophysiological recordings provide unique access to human cortical dynamics but remain difficult to translate across patients due to inconsistent localization of transient surface electrodes. Unlike chronic implantations, intraoperative electrodes are placed transiently, rarely visible on imaging, and often inconsistently documented. We present an open-source imaging pipeline, ALIGNER (Advanced Localization and Imaging Guidance for Neurosurgical Electrode Recording), designed to reconstruct intraoperative surface electrode array placements and quantitatively map neural activity to individualized anatomical and pathological substrates. By enabling anatomical localization of these electrodes, this framework supports systematic analysis of spatial gradients in neural activity relative to pathological tissue. We developed a multimodal reconstruction framework integrating pre- and postoperative MRI and CT, cortical surface modeling, semi-automated pathology segmentation, intraoperative photographs or videos when available, and physics-based electrode modeling. To improve robustness in cases with distorted anatomy, artificial intelligence tools such as SynthSR were used to enable reliable cortical surface reconstruction prior to FreeSurfer processing. A monocular depth-estimation network was incorporated to constrain electrode placement in conjunction with Blender cloth-physics simulation when photographic images were available, while atlas- and note-guided inference supported reconstruction otherwise. The pipeline was applied to 38 neurosurgical patients across drug-resistant epilepsy resection (n = 24), malformation (n = 1), brain tumor (n = 11), and deep brain stimulation (n = 2) cases, achieving some type of reconstruction and electrode localization in all participants. By exporting electrode coordinates for quantitative spatial analyses, including distance-based mapping relative to lesions and resection cavities, ALIGNER enables anatomically grounded and reproducible analysis of intraoperative electrophysiology. This open-source framework provides foundational infrastructure for cancer neuroscience studies of tumor-neuron interactions and establishes a scalable platform for future neurostimulation, implantable neurodevice, and brain-computer interface applications requiring precise anatomical localization.

Sparse and bright labeling of retinal ganglion cell (RGC) is essential for correlating single-cell morphology with brain-wide visual circuitry. This study aimed to develop a cell-type-specific, sparse labeling strategy for parvalbumin-expressing RGCs (PV+ RGCs) in the transgenic mouse retina using recombinant adeno-associated virus (rAAV) and to map the whole-brain projection patterns of single PV+ RGCs via fluorescence micro-optical sectioning tomography (fMOST). A cell-type-specific dual AAV system was employed, co-packaging a Cre-dependent Flpo plasmid and an Flpo-dependent enhanced yellow fluorescent protein (EYFP) plasmid. Key parameters-including the mixing ratio of core plasmids (ranging from 1/100 to 1/1000), gene copy number of Flpo and EYFP (single versus double), and AAV serotype (AAV2.2 versus engineered AAV2.NN)-were systematically optimized. Transduction efficiency and labeling sparsity under each condition were compared. Whole-retina-to-brain imaging was performed using fMOST on samples injected with the optimal condition (AAV2.2-double-1/1000), enabling the reconstruction of complete axonal trajectories of individual PV+ RGCs from the retina to the brain. The sparsity and signal intensity of labeled RGCs varied significantly with the core plasmid ratio, AAV serotype, and gene copy number. The engineered AAV2.NN serotype increased transduction efficiency and labeling density under equivalent conditions, which facilitated the morphological subclassification of PV+ RGCs into ON, ON-OFF, and OFF types based on their stratification relative to ChAT bands. Axonal projections of single PV+ RGCs were successfully traced to the superior colliculus (SC), dorsal and ventral lateral geniculate nuclei (dLGN/vLGN). This viral labeling platform effectively resolves the classical trade-off between sparsity and signal intensity, providing a robust methodology for whole-brain mapping of individual RGC projections. The approach establishes a practical foundation for future mechanistic and therapeutic studies investigating subtype-selective vulnerability in RGCs.

Prader-Willi syndrome (PWS) results from a lack of expression in several paternally inherited, imprinted contiguous genes. Among the genes inactivated in PWS, the Magel2 gene is considered a significant contributor to the etiology of the syndrome. The loss of the Magel2 gene causes abnormalities in growth and fertility and increased adiposity with altered metabolism in adulthood, which aligns with some of the pathologies observed in PWS. Given that anxiety is a prominent phenotypic behavior in PWS, we investigate the role of the Magel2 gene, particularly in hypothalamic POMC neurons innervating the medial amygdala (MeA), in the behavioral phenotypes associated with Prader-Willi Syndrome (PWS). In this study, we used a retrograde AAV containing the Cre recombinase under the control of neuronal Pomc enhancers to genetically eliminate the Magel2 gene in MeA-innervating ARCPomc neurons. Both male and female mice lacking the Magel2 gene in MeA-innervating ARCPomc neurons display no alterations in anxiety-like behavior during the open field test, light/dark test, and elevated plus maze test in the absence of exposure to acute stress. However, male mice with a Magel2 gene deletion in these particular neurons exhibit increased stress-induced anxiety-like behavior and reduce motivation/spatial learning, while female mice do not show these behavioral changes. Our results suggest that the Magel2 gene in ARCPomc neurons, especially in males, influences the impact of stress on anxiety-like behavior and spatial learning deficits associated with a food reward. With the recent approval of a novel treatment for hyperphagia in PWS by the FDA that seems to target the hypothalamic melanocortin system, understanding the cellular mechanisms by which MAGEL2 in ARCPomc neurons innervating the MeA regulates emotional behaviors might help the development of new therapeutic strategies for addressing mental illness in individuals with PWS.

Paired associative stimulation (PAS) is a non-invasive neuromodulation paradigm capable of inducing long-term potentiation (LTP)- or long-term depression (LTD)-like plasticity. It has been used to probe neuroplasticity and corticospinal excitability alterations in Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, existing studies report inconsistent directions and magnitudes of PAS-induced plasticity changes across the AD continuum. We searched PubMed, Web of Science, Embase, and the Cochrane Library from database inception to December 2025. Eligible studies were case-control studies and randomized controlled trials (RCTs) that assessed PAS-induced cortical plasticity in individuals with AD or MCI, with healthy older adults as controls. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS) for non-randomized studies and the Cochrane Risk of Bias tool (RoB 2) for RCTs. This review was registered in PROSPERO (CRD420251178441). Five studies met the inclusion criteria. Four studies quantified motor cortical plasticity using changes in motor-evoked potential (MEP) amplitude (total N = 135; 64 MCI/AD and 71 controls). The pooled analysis showed no significant difference in PAS-induced MEP changes between participants with MCI/AD and healthy controls [mean difference (MD) = 0.06, 95% CI (-0.05, 0.17), p = 0.32]. This pooled estimate was restricted to MEP-based outcomes and should be interpreted as an exploratory synthesis of motor-system readouts rather than definitive evidence of preserved cortical plasticity in MCI or AD. The remaining RCT, which assessed dorsolateral prefrontal cortex (DLPFC) plasticity using a repetitive PAS (rPAS) intervention without MEP outcomes, also found no significant improvement in prefrontal plasticity relative to control stimulation. Based on the currently available MEP-based evidence, PAS-induced motor-system plasticity findings in individuals with MCI or AD remain inconclusive. Given the limited number of studies and heterogeneity in experimental designs, the pooled negative results should not be interpreted as evidence that cortical plasticity is preserved. Corticospinal hyperexcitability and network-level PAS findings should be regarded as preliminary, hypothesis-generating observations requiring validation in larger, longitudinal, and biomarker-characterized cohorts.

Hereditary sensory and autonomic neuropathies (HSANs) are a group of recessive genetic disorders affecting the sensory and autonomic components of the peripheral nervous system (PNS). Compared with somatosensory dysfunctions, the pathogenesis of visceral dysfunction in HSANs remains understudied. This study investigated the neural circuit mechanisms underlying the arrhythmias observed in conditional Dystonin (Dst) gene-trap mice, an animal model of HSAN type VI (HSAN-VI) in which Cre recombinase inactivates Dst expression in selective neural circuits. Inactivation of the Dst gene in PNS neurons using Advillin-Cre caused the degeneration of sensory and sympathetic ganglionic neurons. This was accompanied by arrhythmia, characterized by increased heart rate variability and irregular pulse frequency, which was prominent under isoflurane anesthesia and occurred in the absence of protein aggregate cardiomyopathy. Furthermore, selective inactivation of the Dst gene in PNS sensory neurons using Vglut2-Cre resulted in similar dysregulation of cardiac rhythm. These findings suggest that arrhythmias caused by Dst mutations arise from the disruption of visceral afferent circuits, and that these neural circuits could be potential therapeutic targets for visceral dysfunction in HSAN-VI.

Analysing organelle structures in tissue samples that preserve the in vivo environment, rather than in isolated cells, can provide valuable information on the mechanisms underlying nerve recovery and repair. However, determining organelle ultrastructure within tissue samples remains challenging with conventional microscopic techniques. To address this limitation, volume electron microscopy, particularly focused ion beam/scanning electron microscopy (FIB/SEM), has provided novel insights into organelle morphology, distribution, and membrane contacts, in three-dimensions and even within intact tissues. This review highlights the application of FIB/SEM for exploring the three-dimensional organization of mitochondria in motor neuron cell bodies and along the axon initial segments (AIS), where simultaneous investigation of intracellular and extracellular environments is difficult using other approaches. These analyses have revealed novel findings regarding mitochondrial distribution under healthy conditions and its dramatic alteration following injury, as well as microglial attachment around the AIS. Furthermore, FIB/SEM has enabled detailed characterization of the complex endoplasmic reticulum (ER) architecture within motor neuron cell bodies. Three-dimensional reconstructions have demonstrated a distinct uneven distribution of the ER in healthy neurons and revealed disruption of this organization following injury. In addition, ER-plasma membrane (ER-PM) contacts have been characterized as sheet-like structures, and quantitative analyses have shown significant increases in ER-PM contacts after injury. The novel findings obtained through FIB/SEM provide new perspectives on the cellular mechanisms underlying neuroregeneration and highlight the value of volume electron microscopy in advancing our understanding of nerve repair processes.

Theory of Mind (ToM) is known as the capacity to infer others' thoughts, intentions, and emotions, supported by a distributed neural brain network, including the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), inferior frontal gyrus (IFG), and precuneus. Although the Rock-Paper-Scissors (RPS) game is used to study the cognitive ToM domain, previous fMRI studies had methodological limitations, including lack of appropriate control conditions and the absence of analyses addressing the directionality of BOLD signal changes. The present fMRI study employed a modified RPS paradigm designed to overcome these limitations. Forty-six healthy adults performed the RPS game and a control task. Whole-brain analyses contrasted neural activity and task-modulated functional connectivity (TMFC) between these conditions and examined BOLD signal changes relative to baseline. In contrast to prior findings of BOLD signal suppression below baseline in affective ToM tasks, RPS elicited increased BOLD responses in canonical ToM regions, including the mPFC, bilateral TPJ, IFG, and precuneus, as well as additional frontal, cingulate and visual regions. TMFC analyses converged with these findings, demonstrating increased RPS-related functional interactions between the bilateral TPJ and precuneus with the left IFG, and between the mPFC and the right TPJ with the right IFG. Additionally, greater deactivation (negative BOLD deflection) below baseline during RPS was observed in the midcingulate cortex and opercular regions bilaterally. These findings extend current understanding of ToM network functioning by demonstrating that the engagement of its affective and cognitive domains manifest through TMFC changes and directionally distinct neural responses.

N-methyl-D-aspartate receptor (NMDAR) antagonists, including ketamine, phencyclidine (PCP), and dizocilpine (MK-801), are an important class of drugs that can produce antidepressant, hallucinogenic, dissociative, psychotomimetic, and anesthetic effects in humans and animal models. To understand the effects of NMDAR antagonists on the brain, it is essential to map their actions at cellular resolution. We quantified c-Fos expressing cells in the mouse telencephalon after systemic injection of the potent NMDAR antagonist MK-801 and found a 10-fold higher density of c-Fos in the medial entorhinal cortex (MEC) compared to other regions of the telencephalon. c-Fos density was high in layer 3 of the dorsal MEC but low in other parts of the MEC. Since previous studies have shown that parvalbumin (PV) staining shows a strong dorsal-ventral gradient in the MEC, we investigated the spatial correlation between c-Fos and PV staining. We classified PV neurons based on their level of immunoreactivity and found that high and medium PV neurons were positively correlated with c-Fos density, while low PV neurons were negatively correlated. To understand the temporal correlation of c-Fos and PV staining, we examined their expression patterns after MK-801 injections during postnatal development. PV expression emerged on postnatal day 12, preceding c-Fos expression, which emerged on postnatal day 16. Our results suggest that local circuits comprising specific subtypes of inhibitory and excitatory neurons are critical for generating a sustained neuronal response to NMDAR antagonists. Furthermore, a high density of PV neuron input may be a prerequisite for the induction of c-Fos expression observed in MEC principal neurons. This study contributes to our understanding of how the brain responds to NMDAR antagonists in the developing and adult brain and reveals cell types in the dorsal MEC that are highly sensitive to this class of drugs.

The hermaphroditic Caenorhabditis elegans, with its fully mapped connectome of 302 neurons, offers a paradigmatic example of how a minimal nervous system governs biotic, adaptive, and context-dependent behaviors. In contrast, modern artificial intelligence systems achieve intelligence through scale rather than efficiency, relying instead on massive datasets and artificially engineered architectures. This mini-review explores how Caenorhabditis elegans neural circuits can inform the development of more efficient and flexible artificial neural networks. We highlight recent studies that translate the principles inherent to Caenorhabditis elegans neural circuits into artificial neural network architectures, with applications in machine control and image classification, resulting in enhanced robustness and improved performance. By distilling neural principles from the simplest known nervous system, this mini-review outlines a pathway toward compact, adaptive, and biologically inspired artificial intelligence systems.

The formation of associations, which involves binding disparate pieces of information, is fundamental to constructing episodic memory. This process primarily relies on the neural circuitry within the medial temporal lobe, specifically the hippocampal-parahippocampal network. Within this network, the perirhinal cortex (PER) and the hippocampus (HPC) are recognized as essential components for associative processing. While the traditional dual-pathway model depicts a hierarchically organized, sequential transmission of information along the medial temporal lobe, recent anatomical and functional studies reveal that the PER and HPC are embedded within a far more extensive and complex multi-pathway connectivity architecture. These connections enable parallel and dynamic interactions between PER, HPC, and other medial temporal lobe structures, supporting flexible modes of information processing and integration essential for associative learning. This review systematically re-evaluates the roles of the PER and HPC in associative learning. We begin by advancing the view that the PER acts not as a passive sensory gateway, but as an associative hub for multimodal association formation, whose special local inhibition provides the computational foundation for integrating complex information of both object features, and spatiotemporal context or affective valence. Building on this perspective, we then synthesize evidence on the dynamic interactions between the PER and HPC, encompassing findings from extensive anatomical and electrophysiological studies. Finally, we focus on the HPC, elucidating how it precisely coordinates information from the PER and other regions, with a particular emphasis on the critical regulatory roles played by inhibitory neurons in this integrative process. The reciprocal neuronal connections, coherent neuronal oscillatory activities and shared neuromodulation in the PER-HPC circuit facilitate the integration of associative learning.

Visuomotor interception requires predicting a moving target's future state to compensate for sensorimotor delays. Predictive control has been studied mainly under constant-speed motion. How observers adapt when the temporal structure of target speed (v T ) varies remains unclear. We examined interception across v T profiles within the same individuals: constant, linear-ramp, and nonlinear (sinusoidal and semicircular). Participants intercepted a moving target while eye and hand movements were recorded; on a subset of trials, visual feedback was removed after an observation period to force reliance on internal estimates. Behavior stayed strongly dependent on v T even under transient visual loss, but this dependence was constrained by how v T evolved over time. Removing feedback increased spatial error and gaze-target distance, with modest effects at constant and linear v T and larger errors at nonlinear v T . Speed matching stayed stable, indicating that local velocity estimates are preserved but insufficient to prevent cumulative spatial error under more complex dynamics. Oculomotor measures were more sensitive than manual control, suggesting partially dissociable effectors. A within-cycle matched-velocity test on the linear-ramp data revealed acceleration-deceleration differences at every velocity bin and metric; the representation is velocity-dominated but not velocity-only, and it exploits higher-order kinematic information at least partially. Exploratory pupillometry showed stable pupil size during full visibility and a reduction late in masked trials, with outcome-dependent modulation independent of gaze position at target disappearance. Predictive interception thus relies on velocity-dominated representations that preserve sensitivity to higher-order kinematic information, enabling robust performance across simple motion profiles but imposing limits when target dynamics become nonlinear.

The subiculum is a critical node of the hippocampal formation, integrating multiple circuits-including thalamic inputs and afferents from CA1 and medial entorhinal cortex-and projecting broadly to cortical and subcortical targets. Yet its contribution to spatial coding remains incompletely understood. We recorded single-unit activity in freely moving mice using two complementary electrophysiological approaches: (i) chronic tetrodes targeting CA1 and the dorsal subiculum (SUB), and (ii) 64-channel linear silicon probes targeting dorsal SUB. In addition to place cells, boundary-vector cells (BVCs) and corner cells (CCs), we identified a subset of subicular neurons that exhibited spatially periodic, grid-like firing patterns. This phenomenon was replicated across recording technologies, indicating that periodic coding is a consistent feature of the mouse subiculum. Compared with CA1 place cells, SUB spatial neurons exhibited lower spatial information and reduced within-session stability, suggesting distinct coding regimes across hippocampal subregions. Sampling along the proximodistal axis with probe arrays further revealed that burst propensity correlated positively with spatial information at more distal recording sites, consistent with known physiological gradients in subiculum and echoing relationships seen in CA1. Together, these results expand the repertoire of identified spatial codes in SUB and support the view in which subiculum contributes to geometry- and periodicity-based representations that complement CA1 and entorhinal spatial coding, thereby shaping downstream computations in cortico-subcortical circuits.

Social status profoundly influences animal behavior through neural plasticity, yet the cellular mechanisms that mediate reconfiguration of neuromodulatory systems remain poorly understood. Here, we investigated status-dependent structural changes in the posterior tubercular nucleus (PTN) of adult zebrafish. Animals were assigned to four social conditions: communal, isolated, dominant, or subordinate. Using markers for cell proliferation (PCNA) and birth-dating (BrdU), we demonstrate that social dominance significantly enhances cell proliferation, leading to an increased population of PTN dopaminergic neurons. In contrast, subordinate and isolated fish exhibited suppressed proliferation and elevated expression of superoxide dismutase 1 (SOD1), suggesting that chronic social stress induces an oxidative burden that may lead to neuronal loss. Furthermore, we identified evidence of neurotransmitter phenotypic plasticity; subordinate fish displayed a significantly higher ratio of glutamatergic (vglut2a) to dopaminergic (dat) expression in PTN neurons compared to dominants, suggesting a status-dependent shift in neuromodulatory identity. Multivariate principal component analysis showed distinct neurobiological profiles that separate social ranks, suggesting that status-dependent plasticity is a coordinated multi-modal response whereby increased BrdU and PCNA expression clustered with the dominant profile while increased expression of cellular stress and shift to glutamate cellular identity clustered with social subordinate and isolate profiles. Collectively, our results improve our understanding of how social experience reshapes the zebrafish brain through integrated changes in cell proliferation, cellular shift in neurotransmitter identity and regulation of cellular viability; thus, providing a potential mechanism for the maintenance of stable behavioral phenotypes in competitive social environments.

Atypical action potentials (aAPs) are fast depolarizing electrical spikes recorded from the cell body, with a smaller amplitude. Despite varying in the generating mechanisms, aAPs have been reported in various brain cell types, including neurons, oligodendrocyte precursor cells (OPCs), and glioma cells. In this mini-review, we summarize the mechanisms and physiological functions of aAPs and outline their contributions to neurological diseases, particularly in glioma pathology. aAPs have been observed in mature brains, arising from mechanisms such as ectopic depolarizations and gap junction coupling, thereby supporting synaptic integration and network synchrony. It is also a signature of immature neurons in development. Subsets of NG2+ OPCs and immature oligodendrocyte-lineage cells exhibit state-, region-dependent excitability, ranging from subthreshold depolarizations to AP-like events, with potential roles in neuron-glial communication, ischemic vulnerability, and myelination. Accumulating human studies have demonstrated that glioma cells generate aAPs, while until recently their molecular profile was characterized by patch-seq. In IDH-mutant glioma, aAP cells exhibit a mixed GABAergic and OPC signature. At the leading edge (LE) of IDH-wild-type gliomas, aAPs are present in both adjacent non-tumor cells and glioblastoma cells (GBCs) across diverse GBC states, yet exhibit reduced proliferation and increased inflammatory signaling. In conclusion, aAPs are a recurrent but context-dependent electrophysiological feature observed in subsets of glioma cells, and may indicate an active role in network integration and active release. Dissecting the differential roles of aAP and no-aAP GBCs through targeted manipulations informed by transcriptomic results may reveal crucial mechanisms underlying multifaceted tumor-neuron crosstalk in glioma progression.