Journal of neurophysiology最新文献

Mild traumatic brain injuries (mTBIs) are caused by biomechanical forces being transmitted to the brain, causing neuronal connections to be subjected to sheering forces. The injury severity can be affected by a number of factors that include age and sex, however, there remains a paucity of data on how repeated mTBI (r-mTBI) impacts the female brain. In these studies, male and female juvenile rats [postnatal day (PND) 25-26] were administered a total of eight mTBIs over a 2-day period. Following each mTBI, rats were immediately assessed for acute neurological impairment. After eight mTBIs were completed, the Barnes maze was used to assess spatial learning and memory. Axonal injury was assessed using silver stain histological analyses. We found that injured females exhibited less acute neurological impairment than males. Three days after the final r-mTBI, no significant differences were observed in spatial learning and memory, with all animals showing similar times to locate the escape platform on the reversal trial, additionally there was no main effect of sex in the Barnes maze. Silver stain uptake was significantly increased in the optic tract, corpus callosum, and cortex compared with sham animals at seven days postinjury in a sex-specific manner. Females showed significant increase in all three regions following r-mTBI, whereas males only showed a significant increase in staining in the optic tract. Overall, these findings show that females may be more susceptible to axonal damage than males, and that cognitive deficits were not evident in this population following r-mTBI. These results indicate that there may be benefits in examining biomarkers that reflect axonal injury and the therapies that target reducing axonal degradation.NEW & NOTEWORTHY Diffuse axonal injury is a hallmark feature of all severities of traumatic brain injury (TBI) yet, in preclinical mild (m)TBI research no studies have yet investigated axonal damage with silver stain immunohistochemistry in female animals. This is a critical gap in the literature as recent studies suggest that females experience mTBI more frequently than males. We found that repeated mTBI (r-mTBI) caused significant diffuse axonal injury that was more pronounced in females compared with males.

Human postural control system has the capacity to adapt to balance-challenging perturbations. However, the characteristics and mechanisms of postural adaptation to continuous perturbation under the sensory conflicting environments remain unclear. We aimed to investigate the functional role of oscillatory coupling drive to lower-limb muscles with changes in balance control during postural adaptation under multisensory congruent and incongruent environments. We combined a platform moving sinusoidally (0.24 Hz) along the anterior-posterior (AP) axis and a virtual scene moving sinusoidally (0.24 Hz) either along the AP or the medio-lateral (ML) axis to present a 3-min visual-somatosensory congruent condition (n = 10) or incongruent condition (n = 12), respectively. We analyzed the kinematic data and performed intermuscular coherence analysis of surface EMG data from bilateral lower limbs. We found that the inter-limb coherence was larger under the congruent condition and decreased over the 3-min perturbation, while inter-limb coherence remained low and showed no changes under the incongruent condition over the 3-min perturbation. These results suggest that exposure to the incongruent condition disrupted inter-limb intermuscular coupling. Besides, we found the bilateral intra-limb coherence decreased over 3-min congruent and incongruent perturbation, with the bilateral ankle joint angular velocity decreased and the coupling strength (0.2-0.3 Hz) between whole body sway and sinusoidal stimuli in AP decreased. These findings suggest that continuous exposure to sinusoidal perturbation in AP under congruent and incongruent conditions decreased bilateral intermuscular coupling, contributing to flexibility in the sagittal plane. Overall, we suggested the postural control system adapts context specifically to different sensory environments, with distinct characteristics of neuromuscular control strategies.NEW & NOTEWORTHY Lower limb muscle coordination plays a vital role when facing continuous perturbation by updating sensorimotor mappings. However, it is unclear how muscle coordination adapts to visual-somatosensory congruent and incongruent perturbations. Here, we found that muscle coordination showed context-specific adaptive changes to visual-somatosensory congruent or incongruent environment.

Previous studies have shown that high-gamma (HG) activity in the primary visual cortex (V1) has distinct higher (broadband) and lower (narrowband) components with different functions and origins. However, it is unclear whether similar segregation exists in the primary somatosensory cortex (S1), and the origins and roles of HG activity in S1 remain unknown. Here, we investigate functional roles and origins of HG activity in S1 during tactile stimulation in humans and a rat model. In the human experiment, lower-frequency HG (50-70 Hz, LHG) was more sensitive to sustained tactile intensity compared with higher-frequency HG (70-150 Hz, HHG). HHG activity varied depending on the ratio of low and high mechanical frequencies, with its pattern reflecting a mixture of neural activities corresponding to them. Furthermore, classification analysis revealed that HHG activity contains more information about texture surfaces compared with LHG activity. In the rat experiment, we found that both HHG and LHG activities are strongest in the somatosensory input layer (layer IV), similar to findings in V1. Interestingly, spike-triggered local field potential (stLFP) analysis revealed significant HG oscillations exclusively in layer IV, indicating a dominant coupling between neuronal firing and HG oscillations in this layer. In summary, HHG activity is associated with detecting changes in the rate of contact force and subtle skin deformations whereas LHG activity reflects the absolute amount of applied contact force. Finally, both HHG and LHG originated in layer IV of S1.NEW & NOTEWORTHY We investigated the functional roles and origins of high-gamma (HG) activity in the primary somatosensory cortex (S1). The higher-frequency component of HG activity is associated with detecting changes in the rate of contact force and subtle skin deformations whereas the lower-frequency component reflects the absolute magnitude of the applied contact force. Both types of HG activity were found to originate in layer IV of S1.

Deep brain stimulation (DBS) using electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine is under consideration to improve executive function in patients with dementia. Although some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain. Two-photon in vivo imaging was combined with deep brain stimulation in C57BL/6J mice. Stimulating electrodes were implanted in the subpallidal basal forebrain, and the ipsilateral somatosensory cortex was imaged. Acetylcholine activity was determined using the GRAB_ACh-3.0 acetylcholine receptor sensor, and blood vessels were visualized with Texas red. Experiments manipulating stimulation frequency demonstrated that integrated acetylcholine-induced fluorescence was insensitive to frequency with the same number of pulses, and that maximum peak levels were achieved with frequencies from 60 to 130 Hz. Altering pulse train length indicated that longer stimulation resulted in higher peaks and more activation with sublinear summation. The acetylcholinesterase inhibitor, donepezil, increased the peak response to 600 pulses of stimulation at 60 Hz, and the integrated response increased by 57% with the 2 mg/kg dose and 126% with the 4 mg/kg dose. Acetylcholine levels returned to baseline with a time constant of 14-18 s. Donepezil increases total acetylcholine receptor activation associated with DBS but does not change temporal kinetics. The long time constants observed in the cerebral cortex add to the evidence supporting volume and synaptic neurotransmission.NEW & NOTEWORTHY Peak acetylcholine responses to deep brain stimulation of the subpallidal basal forebrain increases with increased frequency and number of pulses. Long recovery periods in the 10s of seconds support "volume" versus "phasic" transmission of acetylcholine. Donepezil administration enhances the effect of stimulation on cortical acetylcholine release.

The persistent Na⁺ current (I_NaP) is thought to play important roles in many brain regions including the generation of inspiration in the ventral respiratory column (VRC) of mammals. The characterization of the slow inactivation of I_NaP requires long-lasting voltage steps (>1 s), which will increase intracellular Na⁺ and activate the Na⁺/K⁺-ATPase pump current (I_Pump). Thus, I_Pump may contribute to the previously measured slow inactivation of I_NaP and the generation of the inspiratory bursting rhythm. To test this hypothesis, we computationally modeled a respiratory pacemaker neuron that included a noninactivating I_NaP and I_Pump in addition to other basic spike-generating currents. This model produces an inspiration-like bursting rhythm, in which the dynamics of [Na⁺]_i account for burst initiation and termination. We simulated a voltage-clamp experiment measuring the I_NaP inactivation kinetics using our model of noninactivating I_NaP and I_Pump. Consistent with prior measurements in the VRC, we found a sigmoidal inactivation curve and a current that only partially inactivated reaching a minimum inactivation of 0.37. The biexponential time course of inactivation had decay rate constants of 0.45 s and 2.33 s with contributions of 49% and 51%, respectively. The time constant of inactivation was 2.16 s. This decay was caused by the slow growth of I_Pump and the slow hyperpolarization of the Na⁺ reversal potential in response to the growing [Na⁺]_i. We conclude that important biophysical properties previously attributed to the I_NaP may be caused by I_Pump. This has important implications for understanding respiratory rhythmogenesis and other neuronal functions.NEW & NOTEWORTHY The slow inactivation of the persistent Na⁺ current has been implicated in numerous neuronal functions. Our computational approach indicates that voltage-clamp experiments may show a slow inactivation that is actually caused by the Na⁺/K⁺ pump current and a changing Na⁺ reversal potential rather than a slow Na⁺ inactivation process. These results call into question to what extent the slow inactivation of the persistent Na⁺ current is solely important for neuronal functions.

Dendritic spines, small protrusions on neuronal dendrites, play a crucial role in brain function by changing shape and size in response to neural activity. So far, in depth analysis of dendritic spines in human brain tissue is lacking. This study presents a comprehensive analysis of human dendritic spine morphology and density using a unique dataset from human brain tissue from 27 patients (8 females, 19 males, aged 18-71) undergoing tumor or epilepsy surgery at three neurosurgery sites. We used acute slices and organotypic brain slice cultures to examine dendritic spines, classifying them into the three main morphological subtypes: Mushroom, Thin, and Stubby, via 3D reconstruction using ZEISS arivis Pro software. A deep learning model, trained on 39 diverse datasets, automated spine segmentation and 3D reconstruction, achieving a 74% F1-score and reducing processing time by over 50%. We show significant differences in spine density by sex, dendrite type, and tissue condition. Females had higher spine densities than males, and apical dendrites were denser in spines than basal ones. Acute tissue showed higher spine densities compared to cultured human brain tissue. With time in culture, Mushroom spines decreased, while Stubby and Thin spine percentages increased, particularly from 7-9 to 14 days in vitro, reflecting potential synaptic plasticity changes. Our study underscores the importance of using human brain tissue to understand unique synaptic properties and shows that integrating deep learning with traditional methods enables efficient large-scale analysis, revealing key insights into sex- and tissue-specific dendritic spine dynamics relevant to neurological diseases.

The primate brain is a densely interconnected organ whose function is best understood by recording from the entire structure in parallel, rather than parts of it in sequence. However, available methods either have limited temporal resolution (functional magnetic resonance imaging), limited spatial resolution (macroscopic electroencephalography), or a limited field of view (microscopic electrophysiology). To address this need, we developed a volumetric, mesoscopic recording approach (MePhys) by tessellating the volume of a monkey hemisphere with 992 electrode contacts that were distributed across 62 chronically implanted multi-electrode shafts. We showcase the scientific promise of MePhys by describing the functional interactions of local field potentials between the more than 300,000 simultaneously recorded pairs of electrodes. We find that a subanesthetic dose of ketamine -believed to mimic certain aspects of psychosis- can create a pronounced state of functional disconnection and prevent the formation of stable large-scale intrinsic states. We conclude that MePhys provides a new and fundamentally distinct window into brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways.

In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express δ subunits of GABA_A receptors important for slow inhibition. However, the specific contribution of δ-containing GABA_A receptors to the function of PV interneurons in mPFC is unclear. We explored cellular, synaptic, and local-circuit activity in PV interneurons and pyramidal neurons in mouse mPFC after selectively deleting δ subunits in PV interneurons (cKO mice). In current-clamp recordings, cKO PV interneurons exhibited a higher frequency of action potentials and higher input resistance than wild type (WT) PV interneurons. Picrotoxin increased firing and GABA decreased firing in WT PV interneurons but not in cKO PV interneurons. The δ-preferring agonist THIP reduced spontaneous inhibitory postsynaptic currents disproportionately in WT pyramidal neurons compared with cKO pyramidal neurons. In WT slices, depolarizing the network with 400 nM kainate increased firing of pyramidal neurons but had little effect on PV interneuron firing. By contrast, in cKO slices kainate recruited PV interneurons at the expense of pyramidal neurons. At the population level, kainate induced broadband increases in local field potentials in WT but not cKO slices. These results on cells and network activity can be understood through increased excitability of cKO PV interneurons. In summary, our study demonstrates that δ-containing GABA_A receptors in mPFC PV interneurons play a crucial role in regulating their excitability and the phasic inhibition of pyramidal neurons, elucidating intricate mechanisms governing cortical circuitry.

The rolandic beta (13-30 Hz) rhythm recorded over the somatomotor cortices is known to be modified by movement execution and observation. Beta modulation has been considered as a biomarker of motor function in various neurological diseases, and active natural-like movements might offer a clinically feasible method to assess them. While the stability of movement-related beta modulation has been addressed during passive and highly controlled active movements, the test-retest reliability of natural-like movements has not been established. We used magnetoencephalography (MEG) to evaluate the reproducibility of movement-related sensorimotor beta modulation longitudinally over three months in a group of healthy adults (n = 22). We focused on the changes in beta activity both during active grasping movement (beta suppression) and after movement termination (beta rebound). The strengths of beta suppression and rebound were similar between the baseline and follow-up measurements; intraclass correlation coefficient values (0.76-0.96) demonstrated high reproducibility. Our results indicate that the beta modulation in response to an active hand-squeezing task has excellent test-retest reliability: the natural-like active movement paradigm is suitable for evaluating the functional state of the sensorimotor cortex and can be utilized as a biomarker in clinical follow-up studies.