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Biology subjects

Imamura, F.

Publications and source records attributed to Imamura, F..

9 recordsLinked to original sources

Recurrent Spiking Neural Networks for Continuous Motor Control: A Biologically Plausible Model of Motor Cortex

Motor cortex acquires skilled movements through recurrent spiking dynamics and experience-dependent synaptic plasticity, yet how such circuits learn continuous motor control using biologically local signals remains unclear. Here, we develop a recurrent spiking neural network model of motor cortex that addresses both the computational and biological requirements of motor learning. We first analytically derived the recurrent firing-rate state directly from synaptic input and trained the network by implicit differentiation, thereby avoiding backpropagation through long spike trajectories. We then introduced State-Carry Initialization, which enables closed-loop motor control by continuously carrying the ongoing recurrent state across successive actions. Building on this formulation, we devised a learning rule termed Feedback-Spike Nudging (FSN), in which teaching signals are delivered as spikes through a feedback pathway. Synaptic changes depend only on presynaptic activity and the feedback-evoked change in postsynaptic firing, consistent with biological mechanisms of synaptic plasticity in motor cortex. The resulting networks learned continuous motor control through both supervised and reinforcement learning, which could be mapped respectively onto interactions of motor cortex with the cerebellum and basal ganglia. Moreover, the FSN learning rule was consistent with experimental observations of structural spine plasticity in mouse motor cortex. Thus, our study lays a foundation for recurrent spiking models of motor cortex that are biologically grounded at both the functional and anatomical levels.

neuroscience↗

Ground tilt representation in the rodent cerebral cortex

Information about ground tilt at ones location is indispensable for integrating the body with its surrounding environment. However, how ground-tilt information, together with movement and posture information, is represented in the cerebral cortex remains unclear. To address this issue, we developed a new six-degree-of-freedom platform that can rapidly and precisely impart ground motion to head-fixed mice. Using the Diesel2p large field-of-view two-photon mesoscope, we performed calcium imaging to simultaneously capture activity dynamics across broad cortical areas from the frontal to the parietal cortex while driving the platform through various motion patterns. We found a core area for the ground-tilt information at the parietal cortex, although tilt-direction neurons were found across the dorsal cortex. Neuronal populations preserved tilt-direction information within a common low-dimensional manifold across three distinct motion conditions, indicating a condition-invariant tilt code. Furthermore, to investigate shared dynamics across multiple cortical areas, we introduced broadcast- subspace analysis as an extension of communication subspace analysis. This extended framework revealed that tilt information occupied the second principal shared axis, following movement information. These results reveal the core cortical area for processing tilt information, its universal format, and its sharing across the dorsal cortex, thereby providing a framework for cortical information processing that integrates movement, posture, and environment.

neuroscience↗

Independence and Coherence in Temporal Sequence Computation across the Fronto-Parietal Network

Time processing requires distributed and coordinated cortical dynamics. Flexible yet robust temporal representations can arise from two distinct computational modes: a coherence mode, where multiple cortical areas hold the same elapsed-time estimate, and an independence mode, where each area maintains its own local estimate. However, how the brain switches between these modes has remained unknown. Using mesoscale two-photon calcium imaging, we simultaneously recorded neuronal populations in the secondary motor cortex (M2) and posterior parietal cortex (PPC) of mice performing a novel alternating-interval timing task. Both areas encoded elapsed time through similar high-dimensional sequential activity. Decoding analyses revealed that the fronto-parietal network has both independent and coherent temporal codes. Communication-subspace analysis showed that temporal information was distributed across multiple low-variance subspaces, whereas the largest subspace preferentially encoded behaviour. A twin recurrent neural network (RNN) model with sparse inter-RNN connections and shared high-variance noise reproduced these experimental findings. Moreover, perturbations applied along the dominant shared subspace paradoxically enhanced independence between the two networks. Through a mathematical formalization based on the local Lyapunov exponents, we uncovered how perturbations along different subspaces selectively evoke either independent or coherent communication mode. Together, these results reveal a principle by which fronto-parietal circuits achieve robust yet flexible computation through the interplay of sparse coupling and shared global fluctuations.

neuroscience↗

Open-source modular FPGA system for two-photon mesoscope enabling multi-layer, multi-depth neural activity recording and lifetime imaging

Large field-of-view (FOV) two-photon microscopy makes it possible to record a large number of neural activities from multiple brain regions simultaneously. However, the larger the field of view, the longer it takes to scan the entire FOV. To increase imaging speed, we have developed open-source software to digitize analogue signals from a photomultiplier tube using a field-programmable gate array (FPGA) at a rate of 3.2 GS/s. By combining this with a newly developed a circular delay-path module for a custom two-photon mesoscope (Diesel2p), we succeeded in simultaneous recording of >10,000 neurons from the entire bilateral dorsal cortex at up to four depths. We also demonstrated large FOV lifetime imaging using the same system. Our modular, open-source FPGA system can be readily integrated into any type of two-photon microscope and will accelerate the biomedical application of multi-scale two-photon imaging in a wide range of pathophysiological investigations.

neuroscience↗

Efficacy of natural marine sponges as a passive environmental DNA sampler for freshwater fish diversity monitoring

Environmental DNA (eDNA) analysis is a cost-effective and noninvasive tool for species and biodiversity monitoring in aquatic environments. Passive eDNA sampling is a novel alternative to conventional sampling methods such as water filtration. In this study, we examined the efficacy of the sponge skeleton as a passive eDNA sampler for monitoring freshwater fish. The performance of the passive sampling method was compared with that of standard water filtration in a river environment. Five DNA extraction methods were used in three experiments, and a suitable method for DNA extraction from sponge skeleton was identified. Quantitative fish metabarcoding using MiFish primers revealed no significant differences in species richness between the aqueous and passive sampling methods. Although both the sampling methods showed comparable trends in fish community structure, different clusters were identified for water sampling and passive samplers based on the differences in the DNA concentration of each fish species. The fish diversity in the passive samples was comparable among four DNA extraction methods (except for the filtration method) using the direct capture method. Our results demonstrate the efficacy of passive eDNA sampling for monitoring freshwater fish diversity and the potential use of sponge skeletons as absorption materials for passive eDNA samplers.

ecology↗

Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

neuroscience↗

Cross-platform genetic discovery of small molecule products of metabolism and application to clinical outcomes

Circulating levels of small molecules or metabolites are highly heritable, but the impact of genetic differences in metabolism on human health is not well understood. In this cross-platform, genome-wide meta-analysis of 174 metabolite levels across six cohorts including up to 86,507 participants (70% unpublished data), we identify 499 (362 novel) genome-wide significant associations (p<4.9×10-10) at 144 (94 novel) genomic regions. We show that inheritance of blood metabolite levels in the general population is characterized by pleiotropy, allelic heterogeneity, rare and common variants with large effects, non-linear associations, and enrichment for nonsynonymous variation in transporter and enzyme encoding genes. The majority of identified genes are known to be involved in biochemical processes regulating metabolite levels and to cause monogenic inborn errors of metabolism linked to specific metabolites, such as ASNS (rs17345286, MAF=0.27) and asparagine levels. We illustrate the influence of metabolite-associated variants on human health including a shared signal at GLP2R (p.Asp470Asn) associated with higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes risk, and demonstrate beta-arrestin signalling as the underlying mechanism in cellular models. We link genetically-higher serine levels to a 95% reduction in the likelihood of developing macular telangiectasia type 2 [odds ratio (95% confidence interval) per standard deviation higher levels 0.05 (0.03-0.08; p=9.5×10-30)]. We further demonstrate the predictive value of genetic variants identified for serine or glycine levels for this rare and difficult to diagnose degenerative retinal disease [area under the receiver operating characteristic curve: 0.73 (95% confidence interval: 0.70-0.75)], for which low serine availability, through generation of deoxysphingolipids, has recently been shown to be causally relevant. These results show that integration of human genomic variation with circulating small molecule data obtained across different measurement platforms enables efficient discovery of genetic regulators of human metabolism and translation into clinical insights.Competing Interest StatementA.S.B. has received grants from AstraZeneca, Biogen, Bioverativ, Merck, Novartis, and Sanofi. J. D. sits on the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis and the Astra Zeneca Genomics Advisory Board (2018). E.B.F. is an employee and stock holder of Pfizer.View Full Text

genetics↗

Using genetics to disentangle the complex relationship between food choices and health status

Despite food choices being one of the most important factors influencing health, efforts to identify individual food groups and dietary patterns that cause disease have been challenging, with traditional nutritional epidemiological approaches plagued by biases and confounding. After identifying 302 individual genetic determinants of dietary intake in 445,779 individuals in the UK Biobank study, we develop a statistical genetics framework that enables us, to directly assess the impact of food choices on health outcomes. We show that the biases which affect observational studies extend also to GWAS, genetic correlations and causal inference through genetics, which can be corrected by applying our methods. Finally, by applying Mendelian Randomization approaches to the corrected results we identify some of the first robust causal associations between eating patterns and cancer, heart disease, obesity, and several other health related risk factors, distinguishing between the effects of specific foods or dietary patterns.

genetics↗

Narrowly confined and glomerulus-specific onset latencies of odor-evoked calcium transients in the periglomerular cells of the mouse main olfactory bulb

Odor information is transmitted from olfactory sensory neurons to principal neurons at the glomeruli of the olfactory bulb. The intraglomerular neuronal circuit also includes hundreds of GABAergic interneurons referred to as periglomerular (PG) cells. Stimulus selectivity is well correlated among PG cells that are associated with the same glomerulus, consistent with their highly homogeneous sensory inputs. However, much less is known about the temporal aspects of their activity, including the temporal coordination of their odor-evoked responses. As many PG cells within a glomerular module respond to the same stimulus, the extent to which their activity is temporally aligned will affect the temporal profile of their population inhibitory inputs. Using random-access high-speed two-photon microscopy, we recorded the odor-evoked calcium transients of mouse PG cells and compared the onset latency and rise time among neurons putatively associated with the same and different glomeruli. Whereas the overall onset latencies of odor-evoked transients were distributed across a ~150 ms time window, those from cells putatively associated with the same glomerulus were confined to a much narrower window of several tens of milliseconds. This result suggests that onset latency primarily depends on the associated glomerulus. We also observed glomerular specificity in the rise time. The glomerulus-specific temporal pattern of odor-evoked activity implies that the temporal patterns of inhibitory inputs are unique to individual glomerulus-odor pairs, which may contribute to efficient shaping of the temporal pattern of activity in the principal neurons.

neuroscience↗