Publications using TDT

Temporal precision is a determinant of performance in various motor activities. Although the accuracy and precision of timing in activities have been previously measured and quantified, temporal dynamics with flexible precision have not been considered. Here, we examined the temporal dynamics in timed motor activities (timed actions) using a guinea pig model in a behavioural task requiring an animal to control action timing to obtain a water reward. In well-trained animals, momentary variations in timing precision were extracted from the temporal distribution of the timed actions measured over daily 12-h sessions. The resampling of the observed time of action in each session demonstrated significant changes of timing precision within a session. Periods with higher timing precision appeared indiscriminately during the same session, and such periods lasted ~ 20 min on average. We conclude that the timing precision in trained actions is flexible and changes dynamically in guinea pigs. By elucidating the brain mechanisms involved in flexibility and dynamics with an animal model, future studies should establish more effective methods to actively enhance timing precision in our motor activities, such as sports.

Associative learning enables animals to predict rewards or punishments by their associations with predictive stimuli, while non-associative learning occurs without reinforcement. The latter includes latent inhibition (LI), whereby animals learn to ignore an inconsequential 'familiar' stimulus. Individual honey bees display heritable differences in expression of LI. We examined the behavioral and neuronal responses between honey bee genetic lines exhibiting high and low LI. We observed, as in previous studies, that high LI lines learned a familiar odor more slowly than low LI bees. By measuring gustatory responses to sucrose, we determined that perception of sucrose reward was similar between both lines, thereby not contributing to the LI phenotype. We then used extracellular electrophysiology to determine differences in neural responses of the antennal lobe (AL) to familiar and novel odors between the lines. Low LI bees responded significantly more strongly to both familiar and novel odors than the high LI bees, but the lines showed equivalent differences in response to the novel and familiar odors. This work suggests that some effects of genotype are present in early olfactory processing, and those effects could complement how LI is manifested at later stages of processing in brains of bees in the different lines.

Key points Age‐related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age‐related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9–12 kHz cochlear region) decreases by about 30–40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23 ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23 ‐repaired mice (C57BL/6NTac Cdh23+ ), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains. Abstract Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age‐related hearing loss. Here, we have investigated the functional characteristics of IHCs from early‐onset hearing loss mice harbouring the allele Cdh23 ahl (C57BL/6J and C57BL/6NTac), from late‐onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23 ahl mutation (C57BL/6NTac Cdh23+ ) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9–12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30–40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTac Cdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re‐form functional axon‐somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post‐synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re‐establishing the LOC‐IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23 ahl allele but not in C57BL/6NTac Cdh23+ mice, indicating that the MET apparatus directly contributes to the progression of age‐related hearing loss.

Regeneration of auditory hair cells in adult mammals is challenging. It is also difficult to track the sources of regenerated hair cells, especially in vivo. Previous paper found newly generated hair cells in deafened mouse by injecting a DNA methyltransferase inhibitor 5-azacytidine into the inner ear. This paper aims to investigate the cell sources of new hair cells. Transgenic mice with enhanced green fluorescent protein (EGFP) expression controlled by the Sox2 gene were used in the study. A combination of kanamycin and furosemide was applied to deafen adult mice, which received 4 mM 5-azacytidine injection into the inner ear three days later. Mice were followed for 3, 5, 7 and 14 days after surgery to track hair cell regeneration. Immunostaining of Myosin VIIa and EGFP signals were used to track the fate of Sox2-expressing supporting cells. The results show that (i) expression of EGFP in the transgenic mice colocalized the supporting cells in the organ of Corti, and (ii) the cell source of regenerated hair cells following 5-azacytidine treatment may be supporting cells during 5–7 days post 5-azacytidine injection. In conclusion, 5-azacytidine may promote the conversion of supporting cells to hair cells in chemically deafened adult mice.

Rodents engage in active touch using their facial whiskers: they explore their environment by making rapid back-and-forth movements. The fast nature of whisker movements, during which whiskers often cross each other, makes it notoriously difficult to track individual whiskers of the intact whisker field. We present here a novel algorithm, WhiskEras, for tracking of whisker movements in high-speed videos of untrimmed mice, without requiring labeled data. WhiskEras consists of a pipeline of image-processing steps: first, the points that form the whisker centerlines are detected with sub-pixel accuracy. Then, these points are clustered in order to distinguish individual whiskers. Subsequently, the whiskers are parameterized so that a single whisker can be described by four parameters. The last step consists of tracking individual whiskers over time. We describe that WhiskEras performs better than other whisker-tracking algorithms on several metrics. On our four video segments, WhiskEras detected more whiskers per frame than the Biotact Whisker Tracking Tool. The signal-to-noise ratio of the output of WhiskEras was higher than that of Janelia Whisk. As a result, the correlation between reflexive whisker movements and cerebellar Purkinje cell activity appeared to be stronger than previously found using other tracking algorithms. We conclude that WhiskEras facilitates the study of sensorimotor integration by markedly improving the accuracy of whisker tracking in untrimmed mice.

Significance The maintenance of body fluid homeostasis is critical for survival and very subtle deviations from fluid balance can prompt corrective action. These minute changes are detected by first order homeostatic neurons within circumventricular organs of the lamina terminalis but must be passed along to circuitry for motivated behavior. Water-predictive cues evoke robust increases in dopamine signaling in thirsty rats. We demonstrate that this cue-evoked phasic dopamine response is gated by body fluid status, the dipsogenic hormone angiotensin II, and select neurons of the subfornical organ. These data provide critical insight into the conversion of homeostatic imbalance into invigorated action.

Anxiety disorders involve distorted perception of the world including increased saliency of stress-associated cues. However, plasticity in the initial sensory regions of the brain following a fearful experience has never been examined. The cochlear nucleus (CN) is the first station in the central auditory system, with heterogeneous collections of neurons that not only project to but also receive projections from cortico-limbic regions, suggesting a potential for experience-dependent plasticity. Using wireless neural recordings in freely behaving rats, we demonstrate for the first time that neural gain in the CN is significantly altered by fear conditioning to auditory sequences. Specifically, the ventral subnuclei significantly increased firing rate to the conditioned tone sequence, while the dorsal subnuclei significantly decreased firing rate during the conditioning session overall. These findings suggest subregion-specific changes in the balance of inhibition and excitation in the CN as a result of conditioning experience. Heart rate was measured as the conditioned response (CR), which showed that while pre-conditioned stimulus (CS) responding did not change across baseline and conditioning sessions, significant changes in heart rate were observed to the tone sequence followed by shock. Heart-rate findings support acquisition of conditioned fear. Taken together, the present study presents first evidence for potential experience-dependent changes in auditory perception that involve novel plasticity within the first site of processing auditory information in the brain.

The regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and counteract food-reward disorders.

Frameshift mutation caused by small insertions/deletions (indels) often generate truncated and non-functional proteins, which underlies 22% inherited Mendelian disorders in humans. However, there is no efficient in vivo gene therapy strategies available to date, especially in postmitotic systems. Here, we leveraged the non-homologous end joining (NHEJ) mediated non-random editing profiles to compensate the frameshift mutation in a USH1F mouse model – av3j . After treatment by the selected gRNA, about 50% editing products showed reading-frame restoration, and more than 70% targeted hair cells recovered mechanotransduction. In vivo treatment ameliorated the hearing and balance symptoms in homozygous mutant mice. Furthermore, a scale-up analysis of 114 gRNAs targeting 40 frameshift deafness mutations reveals that 65% loci have at least one gRNA with predicted therapeutic potential. Together, our study demonstrates that the NHEJ-mediated frame restoration is a simple and highly efficient therapeutic strategy for small-indel induced frameshift mutations.

Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2 . Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. However, little is known about the consequences of deleting Mecp2 from the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the entire cerebellum, but not from individual cerebellar cell types, causes a delay in motor learning that is overcome by additional training. We also observed irregular firing rates of Purkinje cells and transcriptional misregulation within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome as well as other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes.

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 also plays a role in ciliogenesis, orientation of cilia basal feet, and planar polarity. Sensory cells of the inner ear display unique structural features that underlie their mechanosensitivity. They represent a distinctive form of cellular polarity, known as planar cell polarity (PCP). However, a role for Spag6 in the inner ear has not yet been explored. In the present study, the function of Spag6 in the inner ear was examined using Spag6-deficient mice. Our results demonstrate hearing loss in the Spag6 mutants, associated with abnormalities in cellular patterning, cell shape, stereocilia bundles and basal bodies, as well as abnormally distributed Frizzled class receptor 6 (FZD6), suggesting that Spag6 participates in PCP regulation. Moreover, we found that the sub-apical microtubule meshwork was disrupted. Our observations suggest new functions for Spag6 in hearing and PCP in the inner ear.

Loss of auditory-nerve (AN) afferent cochlear innervation is a prevalent human condition that does not affect audiometric thresholds and therefore remains largely undetectable with standard clinical tests. AN loss is widely expected to cause hearing difficulties in noise, known as “hidden hearing loss,” but support for this hypothesis is controversial. Here, we used operant conditioning procedures to examine the perceptual impact of AN loss on behavioral tone-in-noise (TIN) sensitivity in the budgerigar ( Melopsittacus undulatus ; of either sex), an avian animal model with complex hearing abilities similar to humans. Bilateral kainic acid (KA) infusions depressed compound AN responses by 40–70% without impacting otoacoustic emissions or behavioral tone sensitivity in quiet. Surprisingly, animals with AN damage showed normal thresholds for tone detection in noise (0.1 ± 1.0 dB compared to control animals; mean difference ± SE), even under a challenging roving-level condition with random stimulus variation across trials. Furthermore, decision-variable correlations (DVCs) showed no difference for AN-damaged animals in their use of energy and envelope cues to perform the task. These results show that AN damage has less impact on TIN detection than generally expected, even under a difficult roving-level condition known to impact TIN detection in individuals with sensorineural hearing loss (SNHL). Perceptual deficits could emerge for different perceptual tasks or with greater AN loss but are potentially minor compared with those caused by SNHL. SIGNIFICANCE STATEMENT Loss of auditory-nerve (AN) cochlear innervation is a common problem in humans that does not affect audiometric thresholds on a clinical hearing test. AN loss is widely expected to cause hearing problems in noise, known as “hidden hearing loss,” but existing studies are controversial. Here, using an avian animal model with complex hearing abilities similar to humans, we examined for the first time the impact of an experimentally induced AN lesion on behavioral tone sensitivity in noise. Surprisingly, AN-lesioned animals showed no difference in hearing performance in noise or detection strategy compared with controls. These results show that perceptual deficits from AN damage are smaller than generally expected, and potentially minor compared with those caused by sensorineural hearing loss (SNHL).

Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation. Approach. Adult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At 4 weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles. Main results. In healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10–12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ∼20 and 60 ms, generally following a Gaussian distribution, rising above baseline at time L ON , followed by a peak response ( L p ), and then falling below baseline at time L OFF . EMG responses occurred between L ON and L p ( 25–27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord neurons after a dorsal midline contusion injury. Significance. This study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

Oscillations in the granule cell layer (GCL) of the cerebellar cortex have been related to behavior and could facilitate communication with the cerebral cortex. These local field potential (LFP) oscillations, strong at 4-12 Hz in the rodent cerebellar cortex during awake immobility, should also be an indicator of an underlying influence on the patterns of the cerebellar cortex neuronal firing during rest. To address this hypothesis, cerebellar cortex LFPs and simultaneous single-neuron activity were collected during LFP oscillatory periods in the GCL of awake resting rats. During these oscillatory episodes, different types of units across the GCL and Purkinje cell layers showed variable phase-relation with the oscillatory cycles. Overall, 74% of the Golgi cell firing and 54% of the Purkinje cell simple spike (SS) firing were phase-locked with the oscillations, displaying a clear phase relationship. Despite this tendency, fewer Golgi cells (50%) and Purkinje cell's SSs (25%) showed an oscillatory firing pattern. Oscillatory phase-locked spikes for the Golgi and Purkinje cells occurred towards the peak of the LFP cycle. GCL LFP oscillations had a strong capacity to predict the timing of Golgi cell spiking activity, indicating a strong influence of this oscillatory phenomenon over the GCL. Phase-locking was not as prominent for the Purkinje cell SS firing, indicating a weaker influence over the Purkinje cell layer, yet a similar phase relation. Overall, synaptic activity underlying GCL LFP oscillations likely exert an influence on neuronal population firing patterns in the cerebellar cortex in the awake resting state and could have a preparatory neural network shaping capacity serving as a neural baseline for upcoming cerebellar operations.

Key points Inhibitory‐interneuron networks, consisting of multiple forms of circuit motifs including reciprocal (inhibitory interneurons inhibiting other interneurons) and feedforward (inhibitory interneurons inhibiting principal neurons) connections, are crucial in processing sensory information. The present study applies a statistical method to in vivo multichannel spike trains of dorsal cochlear nucleus neurons to disentangle reciprocal and feedforward‐inhibitory motifs. After inducing input‐specific plasticity, reciprocal and feedforward inhibition are found to be differentially regulated, and the combined effect synergistically modulates circuit output. The findings highlight the interplay among different circuit motifs as a key element in neural computation. Abstract Inhibitory interneurons play an essential role in neural computations by utilizing a combination of reciprocal (interneurons inhibiting each other) and feedforward (interneuron inhibiting the principal neuron) inhibition to process information. To disentangle the interplay between the two inhibitory‐circuit motifs and understand their effects on the circuit output, in vivo recordings were made from the guinea pig dorsal cochlear nucleus, a cerebellar‐like brainstem circuit. Spikes from inhibitory interneurons (cartwheel cell) and principal output neurons (fusiform cell) were compared before and after manipulating their common multimodal input. Using a statistical model based on the Cox method of modulated renewal process of spike train influence, reciprocal‐ and feedforward‐inhibition motifs were quantified. In response to altered multimodal input, reciprocal inhibition was strengthened while feedforward inhibition was weakened, and the two motifs combined to modulate fusiform cell output and acoustic‐driven responses. These findings reveal the cartwheel cell's role in auditory and multimodal processing, as well as illustrated the balance between different inhibitory‐circuit motifs as a key element in neural computation.

Background This study aimed to investigate the changes in the expression of hippocampal genes upon acute noise exposure. Methods Three-week-old Sprague–Dawley rats were assigned to control (n = 15) and noise (n = 15) groups. White noise (2–20 kHz, 115 dB sound pressure level [SPL]) was delivered for 4 h per day for 3 days to the noise group. All rats were sacrificed on the last day of noise exposure, and gene expression in the hippocampus was analyzed using a microarray. Pathway analyses were conducted for genes that showed differential expression ≥ 1.5-fold and P ≤ 0.05 compared to the control group. The genes included in the putative pathways were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results Thirty-eight upregulated genes and 81 downregulated genes were identified. The pathway analyses revealed that upregulated genes were involved in the cellular responses to external stimuli and immune system pathways. qRT-PCR confirmed the upregulation of the involved genes. The downregulated genes were involved in neuronal systems and synapse-related pathways, and qRT-PCR confirmed the downregulation of the involved genes. Conclusions Acute noise exposure upregulated the expression of immune-related genes and downregulated the expression of neurotransmission-related genes in the hippocampus.

Introduction Angelman syndrome (AS) is a neurodevelopmental disorder characterized by motor deficits, seizures, some autistic‐like behaviors, and severe impairment of speech. A dysfunction of the maternally imprinted UBE3A gene, coupled with a functional yet silenced paternal copy, results in AS. Although studies of transgenic mouse models have revealed a great deal about neural populations and rescue timeframes for specific features of AS, these studies have largely failed to examine intermediate phenotypes that contribute to the profound communicative disabilities associated with AS. Methods Here, we use a variety of tasks, including assessments of rapid auditory processing and social communication. Expressive vocalizations were directly assessed and correlated against other core behavioral measures (motor, social, acoustic perception) to model putative influences on communication. Results AS mice displayed the characteristic phenotypes associated with Angelman syndrome (i.e., social and motor deficits), as well as marginal enhancements in rapid auditory processing ability. Our characterization of adult ultrasonic vocalizations further showed that AS mice produce fewer vocalizations and vocalized for a shorter amount of time when compared to controls. Additionally, a strong correlation between motor indices and ultrasonic vocalization output was shown, suggesting that the motor impairments in AS may contribute heavily to communication impairments. Conclusion In summary, the combination of motor deficits, social impairment, marginal rapid auditory enhancements, and altered ultrasonic vocalizations reported in a mouse model of AS clearly parallel the human symptoms of the disorder. This mouse model offers a novel route to interrogate the underlying genetic, physiologic, and behavioral influences on the under‐studied topic of impaired communication in AS.

Significance: Speech processing tasks can be used to assess the integrity and health of many functional and structural aspects of the brain. Despite the potential merits of such behavioral tests as clinical assessment tools, however, the underlying neural substrates remain relatively unclear. Aim: We aimed to obtain a more in-depth portrait of hemispheric asymmetry during dichotic listening tasks at the level of the prefrontal cortex, where prior studies have reported inconsistent results. Approach: To avoid central confounds that limited previous studies, we used diffuse correlation spectroscopy to optically monitor cerebral blood flow (CBF) in the dorsolateral prefrontal cortex during dichotic listening tasks in human subjects. Results: We found that dichotic listening tasks elicited hemispheric asymmetries in both amplitude as well as kinetics. When listening task blocks were repeated, there was an accommodative reduction in the response amplitude of the left, but not the right hemisphere. Conclusions: These heretofore unobserved trends depict a more nuanced portrait of the functional asymmetry that has been observed previously. To our knowledge, these results additionally represent the first direct measurements of CBF during a speech processing task recommended by the American Speech-Language-Hearing Association for diagnosing auditory processing disorders.

Neuromodulation can be used to control organ function through exogenous augmentation of neural activity via targeted delivery of an electrical stimulus. Recently, neuromodulation has been a topic of investigation to treat many illnesses and conditions including Parkinson’s disease, epilepsy, obesity, chronic pain, type 1 diabetes, and hypertension. During neuromodulatory treatments, it is important to measure both the physiological response of the target system as well as any off-target systems that may be engaged from the delivered stimulus. Stimulation of the vagus nerve, a common target of neuromodulatory therapies, causes a vasovagal response which results in decreased cardiac rate and arteriolar dilatation. It is possible to measure these physiological parameters in anesthetized rats, but it is a challenge in conscious, moving rats because of motion artifact introduced to the sensors. By creating a noninvasive, stabilized pulse oximeter that measures the blood oxygenation waveform, one can analyze the heart rate in awake behaving animals. This study reports the design of a heart rate monitor used to monitor effects of heart rate variability during neuromodulation experiments. Design of this device included testing different sensors, methods of attaching to the rodent, microcontrollers, and wireless communication modules.

Irreversible brain injury and neurological dysfunction induced by cardiac arrest (CA) have long been a clinical challenge due to lack of effective therapeutic interventions to reverse neuronal loss and prevent secondary reperfusion injury. The neuronal regenerative potential of neural stem cells (NSCs) provides a possible solution to this clinical deficit. We investigated the neuronal recovery potential of human neural stem cells (hNSCs) via intracerebroventricular (ICV) xenotransplantation after CA in rats and the effects of transplanted NSCs on the proliferation and migration of endogenous NSCs. Outcome measures included neurological functional recovery measured by neurological deficit score (NDS), electrophysiologic analysis of EEG, and assessment of proliferation and migration at the cellular level and the Wnt/β-catenin pathway at the molecular level. Neurological functional assessment based on aggregate neurological deficit score (NDS) showed better recovery of function after hNSCs therapy (P < 0.05). Tracking of stem cells' proliferation with Ki67 antibody suggested that the NSCs group had more prominent proliferation compared to control group (number of Ki67+ cells, Control VS. NSC: 89.0 ± 31.6 VS. 352.7 ± 97.3, P < 0.05). In addition, cell migration tracked by Dcx antibody showed more Dcx + cells migrated to the far distance zone from SVZ in the treatment group (P < 0.05). Further immunofluorescence staining confirmed that the expression of the Wnt signaling pathway protein (β-catenin) was upregulated in the NSC group (P < 0.05). ICV delivery of hNSCs promotes endogenous NSC proliferation and migration and ultimately enhances neuronal survival and neurological functional recovery. Wnt/β-catenin pathway may be involved in the initiation and maintenance of this enhancement.Graphical abstract.