Frontiers in Neural Circuits最新文献

The 8 Hz theta rhythm observed in hippocampal local field potentials of animals can be regarded as a "clock" that regulates the timing of spikes. While different interneuron sub-types synchronously phase lock to different phases for every theta cycle, the phase of pyramidal neurons' spikes asynchronously vary in each theta cycle, depending on the animal's position. On the other hand, pyramidal neurons tend to fire slightly faster than the theta oscillation in what is termed hippocampal phase precession. Chimera states are specific solutions to dynamical systems where synchrony and asynchrony coexist, similar to coexistence of phase precessing and phase locked cells during the hippocampal theta oscillation. Here, we test the hypothesis that the hippocampal phase precession emerges from chimera dynamics with computational modeling. We utilized multiple network topologies and sizes of Kuramoto oscillator networks that are known to collectively display chimera dynamics. We found that by changing the oscillators' intrinsic frequency, the frequency ratio between the synchronized and unsynchronized oscillators can match the frequency ratio between the hippocampal theta oscillation (≈ 8 Hz) and phase precessing pyramidal neurons (≈ 9 Hz). The faster firing population of oscillators also displays theta-sequence-like behavior and phase precession. Finally, we trained networks of spiking integrate-and-fire neurons to output a chimera state by using the Kuramoto-chimera system as a dynamical supervisor. We found that the firing times of subsets of individual neurons display phase precession.

The 5-HT_2C 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-HT_2C receptor. In injured mice, further research is needed to determine whether the expression of the 5-HT_2C 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-HT_2C 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-HT_2C 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-HT_2C receptor in both the lumbar and sacral spinal cord, with female KO mice exhibiting a compensatory mechanism post-SCI via upregulation of the 5-HT_2A receptor. Through a comprehensive approach combining behavioral assessments, electrophysiological experiments, and whole-tissue protein analysis, our findings provide strong evidence that the 5-HT_2C 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-HT_2C receptor account for sex-specific differences in 5-HT_2C receptor expression and function.

Aggregation of the protein tau is a key pathological hallmark of tauopathies such as Alzheimer's Disease. Tau dissociates from microtubules and diffuses from the axon into the soma-dendritic compartment, where it aggregates firstly into oligomers and ultimately into neurofibrillary tangles. There is gathering evidence that it is the soluble tau aggregates that are the major active species and that their effects on neuronal electrophysiological properties, synaptic transmission and plasticity could contribute to early cognitive decline. Here we have investigated the effects of incubating acute mouse hippocampal slices with recombinant tau aggregates. We observed interictal events and an increase in excitability of CA3 pyramidal cells. Tau aggregates had little effect on basal synaptic transmission but antagonism of GABA_A receptors revealed significant effects of tau aggregates, enhancing the firing of population spikes and the occurrence of bursts following fEPSPs. Tau aggregates produced a concentration-dependent impairment of long-term potentiation (LTP), which could not be overcome by repeated LTP induction stimuli, demonstrating the effects were not just through an elevation of LTP threshold. In contrast to the impairment of LTP, tau aggregates increased G1-mGluR-dependent LTD. Thus, tau aggregates increase hippocampal circuit excitability and shift synaptic plasticity towards depression.

The regulatory mechanisms of postnatal neurogenesis in the subventricular zone (SVZ) and the rostral migratory stream (RMS) are still not fully understood. Recent evidence suggests that neurogenesis in the SVZ/RMS may be regulated by neurons located directly in these regions. To date, two populations of neurons residing in the SVZ/RMS, which display the morphological characteristics of mature neurons, have been identified: nitric oxide (NO)-producing neurons and neurons expressing secretagogin (SCGN). The aim of our study was to map the possible projections of these neuronal populations in the SVZ/RMS. All experiments were performed on adult male Wistar albino rats. To test the hypothesis that nNOS- and SCGN-positive neurons of the SVZ and RMS send their axons to the striatum, we injected this target brain structure with the retrograde fluorescent tracer Fluoro-Gold (F-G). To verify the identity of nitrergic neurons and SCGN- expressing neurons, double immunofluorescent labeling with anti-nNOS/anti-SCGN and anti-F-G was performed. Microscopic analysis revealed the presence of F-G, administered into the striatum, in cells of the SVZ and different parts of the RMS. F-G-labeled cells in the SVZ/RMS were identified as either nitrergic neurons or SCGN-expressing neurons. Our results demonstrate a connection between mature neurons of the SVZ/RMS and the striatum.

Aligning the topography maps of different sensory modalities in the brain is considered to be important for the unified perception of multiple sensory modalities. In mice, the superior colliculus receives both visual and whisker-related somatosensory information with the topographical correspondence between retinotopy and somatotopy. However, it remains unclear whether topographical correspondence between retinotopy and whisker somatotopy exists in the higher association cortex, and if so, how this functional organization is formed during development. Here, we conducted wide-field calcium imaging and revealed retinotopic and somatotopic correspondence in the rostrolateral area (RL), one of the higher visual areas. The retinotopic map demonstrates that RL is divided into two distinct subregions, anterior and posterior parts of RL (RLa and RLp). We further found a rough topographic correspondence between retinotopy and whisker somatotopy only in RLa, but not in RLp, Lastly, to test whether this topographic correspondence exists before eye-opening, we performed functional connectivity analysis of spontaneous cortical activity recorded from developing mice. We discovered that the topographical correspondence between retinotopy-like and somatotopy-like structures in RLa already existed before eye-opening, on postnatal day 10-11. Because spatially corresponding multisensory inputs are likely quite weak before eye-opening, these results in developing mice suggest that the initial formation of topographic correspondence between retinotopy and whisker somatotopy in the higher association cortex does not depend on spatially corresponding multisensory input experiences.

How can we make sense of large-scale recordings of neural activity across learning? Theories of neural network learning with their origins in statistical physics offer a potential answer: for a given task, there are often a small set of summary statistics that are sufficient to predict performance as the network learns. Here, we review recent advances in how summary statistics can be used to build theoretical understanding of neural network learning. We then argue for how this perspective can inform the analysis of neural data, enabling better understanding of learning in biological and artificial neural networks.

The fine-scale organization of intrinsic and extrinsic connections in the primate ventrolateral prefrontal cortex (VLPFC), a region essential for higher cognitive functions, remains poorly understood. This contrasts with, for example, the well-documented stripe-like intrinsic circuits of the dorsolateral prefrontal cortex (DLPFC). To elucidate the circuit architecture supporting VLPFC function, we investigated the spatial organization of connections targeting the caudal VLPFC (primarily area 45A) in macaque monkeys using multiple retrograde tracers. Analyzing the distribution of labeled neurons in flattened tangential sections revealed that laterally projecting connections within the same hemisphere formed distinct clusters, not only in the VLPFC but also in the DLPFC. These clusters often spanned multiple cortical layers, suggesting a columnar-like organization. The width (minor axis) of these clusters was approximately 1.2 mm. Similarly, contralateral callosal projection neurons were also arranged in clusters. Additionally, inputs originating from the superior temporal sulcus were found to arise from discrete clusters of neurons. Our findings demonstrate that both long-range ipsilateral and interhemispheric connections of the caudal VLPFC share a common, fine-scale clustered architecture. This study provides an anatomical framework for understanding the structural basis of information processing and interhemispheric coordination within this critical association cortex, suggesting that this architecture is fundamental to VLPFC's role in complex cognitive functions.

Neuronal networks in animal brains are considered to realize specific filter functions through the precise configuration of synaptic weights, which are autonomously regulated without external supervision. In this study, we employ a single Hodgkin-Huxley-type neuron with autapses as a minimum model to computationally investigate how spike-timing-dependent plasticity (STDP) adjusts synaptic weights through recurrent feedback. The results show that the weights undergo oscillatory potentiation or depression with respect to autaptic delay and high-frequency stimulation. Our findings suggest that the STDP-mediated modulation of autaptic weights, governed by autaptic delay and input frequency, may serve as a mechanism for promoting network-level synchronization in neural systems if the network contains neurons with autapses.

Introduction: Understanding how neural networks process complex patterns of information is crucial for advancing both neuroscience and artificial intelligence. To investigate fundamental principles of neural computation, we examined whether dissociated neuronal cultures, one of the most primitive living neural networks, exhibit regularity sensitivity beyond mere stimulus-specific adaptation and deviance detection.

Methods: We recorded activity to oddball electrical stimulation paradigms from dissociated rat cortical neurons cultured on high-resolution CMOS microelectrode arrays. We examined the effects of pharmacological manipulation on responses using the N-methyl-D-aspartate (NMDA) receptor antagonist. To assess regularity sensitivity, we compared neural responses between predictable periodic sequences and random sequences of stimuli.

Results: In oddball electrical stimulation paradigms, we confirmed that the neuronal culture produced mismatch responses (MMRs) with true deviance detection beyond mere adaptation. These MMRs were dependent on the N-methyl-D-aspartate (NMDA) receptors, similar to mismatch negativity (MMN) in humans, which is known to have true deviance detection properties. Crucially, we also showed sensitivity to the statistical regularity of stimuli, a phenomenon previously observed only in intact brains: the MMRs in a predictable, periodic sequence were smaller than those in a commonly used sequence in which the appearance of the deviant stimulus was random and unpredictable.

Discussion: These results challenge the traditional view that a hierarchically structured neural network is required to process complex temporal patterns, suggesting instead that deviant detection and regularity sensitivity are inherent properties arising from the primitive neural network. They also suggest new directions for the development of neuro-inspired artificial intelligence systems, emphasizing the importance of incorporating adaptive mechanisms and temporal dynamics in the design of neural networks.

Neural circuits sculpt their structure and modify the strength of their connections to effectively adapt to the external stimuli throughout life. In response to practice and experience, the brain learns to distinguish previously undetectable stimulus features recurring in the external environment. The unconscious acquisition of improved perceptual abilities falls into a form of implicit learning known as perceptual learning. Despite more than a century of multidisciplinary studies, a thorough understanding of the neural mechanisms underlying perceptual learning is still missing. Increasing evidence suggests that the learning process induces global plastic remodeling across several cortical areas, tuning neural responses to changing environmental claims by reweighting the interaction between bottom-up and top-down information. Here, we will survey classic and novel findings in the field of perceptual learning research, with a particular focus on visual perceptual learning.