Frontiers in Neural Circuits最新文献

There is evidence that stress factors and negative experiences in early in life may affect brain development leading to mental disorders in adulthood. At the early stage of postnatal ontogenesis, the central nervous system has high plasticity, which decreases with maturation. Most likely, this high plasticity is necessary for establishing synaptic connections between different types of neurons, regulating the strength of individual synapses, and ultimately forming properly functioning neuronal networks. The vast majority of studies have examined the effects of early-life stress (ELS) on gene expression or behavior and memory. However, the impact of ELS on functional synaptic development and on the plastic properties of excitatory and inhibitory synapses are currently much less understood. Based on data obtained in a few studies it has been suggested that ELS reduces long-term potentiation (LTP) at Schaffer collateral to CA1 pyramidal cell synapses in adulthood. Nevertheless, different groups have reported somewhat contradictory results. In this report we show that ELS differentially affects LTP at CA3 to CA1 pyramidal cell inputs, at synapses on apical dendrites LTP is reduced, while LTP at synapses formed by CA3 pyramidal cells on basal dendrites remains unaffected.

During the early postnatal period, neurons in sensory circuits dynamically remodel their connectivity to acquire discrete receptive fields. Neuronal activity is thought to play a central role in circuit remodeling during this period: Neuronal activity stabilizes some synaptic connections while eliminating others. Synaptic competition plays a central role in the binary choice between stabilization and elimination. While activity-dependent "punishment signals" propagating from winner to loser synapses have been hypothesized to drive synapse elimination, their exact nature has remained elusive. In this review, I summarize recent studies in mouse mitral cells that explain how only one dendrite is stabilized while others are eliminated, based on early postnatal spontaneous activity in the olfactory bulb. I discuss how the hypothetical punishment signals act on loser but not winner dendrites to establish only one primary dendrite per mitral cell, the anatomical basis for the odorant receptor-specific parallel information processing in the olfactory bulb.

Introduction: Neural circuits develop during critical periods (CPs) and exhibit heightened plasticity to adapt to the surrounding environment. Accumulating evidence indicates that the maturation of inhibitory circuits, such as gamma-aminobutyric acid and parvalbumin-positive interneurons, plays a crucial role in CPs and contributes to generating gamma oscillations. A previous theory of the CP mechanism suggested that the maturation of inhibition suppresses internally driven spontaneous activity and enables synaptic plasticity to respond to external stimuli. However, the neural response to external stimuli and neuronal oscillations at the neural population level during CPs has not yet been fully clarified. In the present study, we aimed to investigate neuronal activity responsiveness with respect to the maturation of inhibition at gamma-band frequencies.

Method: We calculated inter-trial phase coherence (ITPC), which quantifies event-related phase modulations across trials, using a biologically plausible spiking neural network that generates gamma oscillations through interactions between excitatory and inhibitory neurons.

Results: Our results demonstrated that the neuronal response coherence to external periodic inputs exhibits an inverted U-shape with respect to the maturation of inhibition. Additionally, the peak of this profile was consistent with the moderate suppression of the gamma-band spontaneous activity.

Discussion: This finding suggests that the neuronal population's highly reproducible response to increased inhibition may lead to heightened synaptic plasticity. Our computational model can help elucidate the underlying mechanisms that maximize synaptic plasticity at the neuronal population level during CPs.

Introduction: Spinal cord injury in the high cervical cord can impair breathing due to disruption of pathways between brainstem respiratory centers and respiratory motor neurons in the spinal cord. Electrical stimulation of limb afferents can increase ventilation in healthy humans and animals, but it is not known if limb afferent stimulation can improve breathing following a cervical injury.

Methods: We stimulated the sciatic nerve while using electromyography to measure diaphragm function in anesthetized mice following a cervical (C2) hemisection spinal cord injury, as well as in uninjured controls. The amplitude and frequency of inspiratory bursts was analyzed over a range of stimulation thresholds.

Results: We show that electrical stimulation (at sufficient current thresholds) of either the left or right sciatic nerve could restore inspiratory activity to the previously paralyzed diaphragm ipsilateral to a C2 hemisection injury at either acute (1 day) or chronic (2 months) stages after injury. We also show that sciatic nerve stimulation can increase the frequency and amplitude of diaphragm inspiratory bursts in uninjured mice.

Discussion: Our findings indicate that therapies targeting limb afferents could potentially be used to improve breathing in patients with cervical spinal cord injury and provide an experimental model to further investigate the neural pathways by which limb afferents can increase respiratory muscle activity.

Extracellular brain space contains water, dissolved ions, and multiple other signaling molecules. The neural extracellular matrix (ECM) is also a significant component of the extracellular space. The ECM is synthesized by neurons, astrocytes, and other types of cells. Hyaluronan, a hyaluronic acid polymer, is a key component of the ECM. The functions of hyaluronan include barrier functions and signaling. In this article, we investigate physiological processes during the acute phase of enzymatic ECM removal. We found that hyaluronidase, an ECM removal agent, triggers simultaneous membrane depolarization and sharp calcium influx into neurons. Spontaneous action potential firing frequency increased rapidly after ECM destruction in interneurons, but not pyramidal neurons. Hyaluronidase-dependent calcium entry can be blocked by a selective antagonist of N-methyl-D-aspartate (NMDA) receptors, revealing these receptors as the main player in the observed phenomenon. Additionally, we demonstrate increased NMDA-dependent long-term potentiation at CA3-to-CA1 synapses during the acute phase of ECM removal. These findings suggest that hyaluronan is a significant synaptic player.

The substantia nigra pars compacta (SNc), one of the main dopaminergic nuclei of the brain, exerts a regulatory function on the basal ganglia circuitry via the nigro-striatal pathway but its possible dopaminergic innervation of the thalamus has been only investigated in non-human primates. The impossibility of tract-tracing studies in humans has boosted advanced MRI techniques and multi-shell high-angular resolution diffusion MRI (MS-HARDI) has promised to shed more light on the structural connectivity of subcortical structures. Here, we estimated the possible dopaminergic innervation of the human thalamus via an MS-HARDI tractography of the SNc in healthy human young adults. Two MRI data sets were serially acquired using MS-HARDI schemes from ADNI and HCP neuroimaging initiatives in a group of 10 healthy human subjects (5 males, age range: 25-30 years). High resolution 3D-T1 images were independently acquired to individually segment the thalamus and the SNc. Starting from whole-brain probabilistic tractography, all streamlines through the SNc reaching the thalamus were counted, separately for each hemisphere, after excluding streamlines through the substantia nigra pars reticulata and all those reaching the basal ganglia, the cerebellum and the cortex. We found a reproducible structural connectivity between the SNc and the thalamus, with an average of ~12% of the total number of streamlines encompassing the SNc and terminating in the thalamus, with no other major subcortical or cortical structures involved. The first principal component map of dopamine receptor density from a normative PET image data set suggested similar dopamine levels across SNc and thalamus. This is the first quantitative report from in-vivo measurements in humans supporting the presence of a direct nigro-thalamic dopaminergic projection. While histological validation and concurrent PET-MRI remains needed for ultimate proofing of existence, given the potential role of this pathway, the possibility to achieve a good reproducibility of these measurements in humans might enable the monitoring of dopaminergic-related disorders, towards targeted personalized therapies.

A strong repetitive stimulus can occasionally enhance axonal excitability, leading to the generation of afterdischarge. This afterdischarge outlasts the stimulus period and originates either from the physiological spike initiation site, typically the axon initial segment, or from ectopic sites for spike generation. One of the possible mechanisms underlying the stimulus-induced ectopic afterdischarge is the local depolarization due to accumulated potassium ions surrounding the axonal membranes of the distal portion. In this study, the mechanisms were explored by computational approaches using a simple model of hippocampal mossy fibers implemented with the structure of en passant axons and experimentally obtained properties of ionic conductances. When slight depolarization of distal axons was given in conjunction with the high-frequency stimulus, robust afterdischarges were triggered after cessation of the repetitive stimulus and lasted for a prolonged period after the stimulus. Each spike during the afterdischarge recorded from distal axons precedes that recorded from the soma, suggesting that the afterdischarge was ectopically generated from distal axons and propagated antidromically toward the soma. Notably, when potassium channels in the model are replaced with non-inactivating ones, repetitive stimuli fail to induce afterdischarge. These results suggested that the inactivating property of axonal potassium channels plays a crucial role in generating the afterdischarge. Accumulated inactivation of potassium channels during strong repetitive stimulation may alter mossy fiber excitability, leading to ectopic afterdischarges from sites distinct from the physiological spike initiation region.

Introduction: Motor-imagery-based Brain-Machine Interface (MI-BMI) has been established as an effective treatment for post-stroke hemiplegia. However, the need for long-term intervention can represent a significant burden on patients. Here, we demonstrate that motor imagery (MI) instructions for BMI training, when supplemented with somatosensory stimulation in addition to conventional verbal instructions, can help enhance MI capabilities of healthy participants.

Methods: Sixteen participants performed MI during scalp EEG signal acquisition before and after somatosensory stimulation to assess MI-induced cortical excitability, as measured using the event-related desynchronization (ERD) of the sensorimotor rhythm (SMR). The non-dominant left hand was subjected to neuromuscular electrical stimulation above the sensory threshold but below the motor threshold (St-NMES), along with passive movement stimulation using an exoskeleton. Participants were randomly divided into an intervention group, which received somatosensory stimulation, and a control group, which remained at rest without stimulation.

Results: The intervention group exhibited a significant increase in SMR-ERD compared to the control group, indicating that somatosensory stimulation contributed to improving MI ability.

Discussion: This study demonstrates that somatosensory stimulation, combining electrical and mechanical stimuli, can improve MI capability and enhance the excitability of the sensorimotor cortex in healthy individuals.

According to the World Health Organization, the number of people suffering from depressive disorders worldwide is approaching 350 million. The consequences of depressive disorders include considerable worsening of the quality of life, which frequently leads to social isolation. One of the key factors which may cause depression in adulthood is early life stress, in particular, insufficient maternal care during infancy. Studies performed with children raised in orphanages have shown that long-term complete absence of maternal care (chronic early life stress) leads to vulnerability to emotional disorders, including depression, in adulthood. All of the above dictates the need for a deep understanding of the mechanisms of the pathogenicity of stress in neurogenesis. Therefore, the consequences of stress experienced in the early stages of development are actively studied in animal models. A large body of evidence has accumulated indicating stress-induced changes in gene expression and behavioral disorders in adulthood. However, the connection between the molecular biology of neurons and complex behavior runs through the synaptic connections linking these neurons into complex neural networks. In turn, coordinated activity in neuronal ensembles, achieved by a balance of synaptic excitation and inhibition, is the basis of complex behavior. Unfortunately, the effect of stress on synaptic interactions of neurons remains poorly understood.