Frontiers in Neural Circuits最新文献

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.

Introduction: 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).

Methods: 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.

Results: Both male and female mice lacking the Magel2 gene in MeA-innervating ARC^Pomc 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 ARC^Pomc neurons, especially in males, influences the impact of stress on anxiety-like behavior and spatial learning deficits associated with a food reward.

Discussion: 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 ARC^Pomc neurons innervating the MeA regulates emotional behaviors might help the development of new therapeutic strategies for addressing mental illness in individuals with PWS.

Introduction: Motor tasks require the flexible selection and coordination of multiple muscles, which may be achieved through the organization and combination of muscle synergies. Although multiple muscles may receive a shared neural drive, and each muscle may also receive distinct neural inputs, there is ongoing debate about whether synergies accurately reflect shared neural drives. This study aimed to compare the spectral characteristics of the common drive shared among muscles within the same synergy to those shared among muscles belonging to different synergies.

Methods: Electromyographic signals were recorded from upper limb muscles during an isometric multi-directional force generation task. Synergies were identified using non-negative matrix factorization (NMF), and coherence analysis was conducted to evaluate common drives among muscles within and across synergies. A methodological limitation of previous studies was to segment muscle activity into standard frequency bands. Here, we overcome it by proposing to automatically detect subject-specific and physiologically relevant frequency layers. The application of NMF on the coherence spectra of muscle pairs as a method for automatically detecting physiologically relevant frequency bands sheds light into the neural basis of muscle coordination.

Results: Six frequency layers were identified, and muscle recruited within the same synergy showed a higher coherence within layers in the delta, alpha, and low-beta bands.

Discussion: Our findings enhance the understanding of physiological mechanisms of motor coordination by elucidating the relationship between muscle synergies and the spectral characteristics of intermuscular coherence.

Unlike digital computers, the brain exhibits spontaneous activity even during complete rest, despite the evolutionary pressure for energy efficiency. Inspired by the critical brain hypothesis, which proposes that the brain operates optimally near a critical point of phase transition in the dynamics of neural networks to improve computational efficiency, we postulate that spontaneous activity plays a homeostatic role in the development and maintenance of criticality. Criticality in the brain is associated with the balance between excitatory and inhibitory synaptic inputs (EI balance), which is essential for maintaining neural computation performance. Here, we hypothesize that both criticality and EI balance are stabilized by appropriate noise levels and spike-timing-dependent plasticity (STDP) windows. Using spiking neural network (SNN) simulations and in vitro experiments with dissociated neuronal cultures, we demonstrated that while repetitive stimuli transiently disrupt both criticality and EI balance, spontaneous activity can develop and maintain these properties and prolong the fading memory of past stimuli. Our findings suggest that the brain may achieve self-optimization and memory consolidation as emergent functions of noise-driven spontaneous activity. This noise-harnessing mechanism provides insights for designing energy-efficient neural networks, and suggest a potential link between the emergent function of spontaneous activity and sleep function in maintaining homeostasis and consolidating memory.

This article aims to provide a synaptic input database called, dendritic synaptome for dendrites of calcium-binding protein-containing interneurons [calbindin-D28K (CB+), calretinin (CR+), parvalbumin (PV+)] employing a modified correlated light and EM method, the "mirror-technique" that allows for investigating neuronal compartments while preserving utmost ultrastructural quality (Talapka et al., 2021). Nine dendrites and all presynaptic boutons (n = 815) impinging on their surface were traced and reconstructed in three-dimensions (3D) using serial section transmission electron microscopy (ssTEM). The following basic parameters of the synapses were determined: The ratio of symmetric ("ss" or putative inhibitory) and asymmetric ("as" or putative excitatory) synapses, the number of synapses per unit length of dendrite (i.e., density of "as" and "ss"), surface area and volume of presynaptic boutons, and area of the active zones of synapses. Significant differences in the morphometric parameters of asymmetric, but not in symmetric, synapses were detected between the three interneuron subtypes. Surface extent and the number of synapses on PV+ dendrites were the largest compared to the other two subtypes. Although the distribution of presynaptic boutons differed between dendrites, clustering of the presynaptic boutons could be revealed only for PV+ dendrites. Based on our serial-section electron microscopy (ssEM) reconstructions and corresponding light microscopy (LM) databases of CBP dendrites, it was calculated that on average a single CB+, CR+, and PV+ interneuron receives 2,136, 2,148, and 2,589 synapses, respectively, of which 74.6, 81.5, and 85.3% are excitatory, that is, asymmetric, and the remaining inhibitory, that is, symmetric. Carriage return findings provide essential quantitative information to establish realistic computational models for studying the synaptic function of neuronal ensembles in the mouse primary visual cortex.

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.

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.