scholarly journals Global organization of neuronal activity only requires unstructured local connectivity

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
David Dahmen ◽  
Moritz Layer ◽  
Lukas Deutz ◽  
Paulina Anna Dąbrowska ◽  
Nicole Voges ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Network Models ◽  
Local Connectivity ◽  
Reach To Grasp ◽  
Electrophysiological Recordings ◽  
Global Organization ◽  
Network States ◽  
Low Dimensional ◽  
Coordination Patterns

Modern electrophysiological recordings simultaneously capture single-unit spiking activities of hundreds of neurons spread across large cortical distances. Yet, this parallel activity is often confined to relatively low-dimensional manifolds. This implies strong coordination also among neurons that are most likely not even connected. Here, we combine in vivo recordings with network models and theory to characterize the nature of mesoscopic coordination patterns in macaque motor cortex and to expose their origin: We find that heterogeneity in local connectivity supports network states with complex long-range cooperation between neurons that arises from multi-synaptic, short-range connections. Our theory explains the experimentally observed spatial organization of covariances in resting state recordings as well as the behaviorally related modulation of covariance patterns during a reach-to-grasp task. The ubiquity of heterogeneity in local cortical circuits suggests that the brain uses the described mechanism to flexibly adapt neuronal coordination to momentary demands.

scholarly journals Long-range coordination patterns in cortex change with behavioral context

2020 ◽  
Author(s):  
David Dahmen ◽  
Moritz Layer ◽  
Lukas Deutz ◽  
Paulina Anna Dąbrowska ◽  
Nicole Voges ◽  
...  
Keyword(s):  
Long Range ◽  
Network Models ◽  
Dependent Manner ◽  
Behavioral Context ◽  
Reach To Grasp ◽  
Long Range Correlations ◽  
State Dependent ◽  
Negative Spike ◽  
Coordination Patterns ◽  
Balanced Network

Cortical connectivity mostly stems from local axonal arborizations, suggesting coordination is strongest between nearby neurons in the range of a few hundred micrometers. Yet multi-electrode recordings of resting-state activity in macaque motor cortex show strong positive and negative spike-count covariances between neurons that are millimeters apart. Here we show that such covariance patterns naturally arise in balanced network models operating close to an instability where neurons interact via indirect connections, giving rise to long-range correlations despite short-range connections. A quantitative theory explains the observed shallow exponential decay of the width of the covariance distribution at long distances. Long-range cooperation via this mechanism is not imprinted in specific connectivity structures but rather results dynamically from the network state. As a consequence, neuronal coordination patterns are not static but can change in a state-dependent manner, which we demonstrate by comparing different behavioral epochs of a reach-to-grasp experiment.

scholarly journals Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

2020 ◽  
Author(s):  
Nora Jamann ◽  
Dominik Dannehl ◽  
Robin Wagener ◽  
Corinna Corcelli ◽  
Christian Schultz ◽  
...  
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Sensory Deprivation ◽  
Axon Initial Segment ◽  
Electrophysiological Recordings ◽  
Network States

SummaryThe axon initial segment (AIS) is an important axonal microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent cortical plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using an in vivo model of the mouse whisker-to-barrel pathway in combination with immunofluorescence, confocal analysis and patch-clamp electrophysiological recordings, we observed bidirectional AIS plasticity. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.

scholarly journals Kilosort: realtime spike-sorting for extracellular electrophysiology with hundreds of channels

2016 ◽  
Author(s):  
Marius Pachitariu ◽  
Nicholas Steinmetz ◽  
Shabnam Kadir ◽  
Matteo Carandini ◽  
Harris Kenneth D.
Keyword(s):  
Large Scale ◽  
Superior Performance ◽  
Spike Sorting ◽  
Electrode Arrays ◽  
Manual Curation ◽  
Electrophysiological Recordings ◽  
Dimensional Approximation ◽  
Low Dimensional ◽  
Channel Electrode

AbstractAdvances in silicon probe technology mean that in vivo electrophysiological recordings from hundreds of channels will soon become commonplace. To interpret these recordings we need fast, scalable and accurate methods for spike sorting, whose output requires minimal time for manual curation. Here we introduce Kilosort, a spike sorting framework that meets these criteria, and show that it allows rapid and accurate sorting of large-scale in vivo data. Kilosort models the recorded voltage as a sum of template waveforms triggered on the spike times, allowing overlapping spikes to be identified and resolved. Rapid processing is achieved thanks to a novel low-dimensional approximation for the spatiotemporal distribution of each template, and to batch-based optimization on GPUs. A novel post-clustering merging step based on the continuity of the templates substantially reduces the requirement for subsequent manual curation operations. We compare Kilosort to an established algorithm on data obtained from 384-channel electrodes, and show superior performance, at much reduced processing times. Data from 384-channel electrode arrays can be processed in approximately realtime. Kilosort is an important step towards fully automated spike sorting of multichannel electrode recordings, and is freely available (github.com/cortex-lab/Kilosort).

scholarly journals Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nora Jamann ◽  
Dominik Dannehl ◽  
Nadja Lehmann ◽  
Robin Wagener ◽  
Corinna Thielemann ◽  
...  
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Sensory Deprivation ◽  
Axon Initial Segment ◽  
Electrophysiological Recordings ◽  
Network States

AbstractThe axon initial segment (AIS) is a critical microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts in vivo as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using the mouse whisker-to-barrel pathway as a model system in combination with immunofluorescence, confocal analysis and electrophysiological recordings, we observed bidirectional AIS plasticity in cortical pyramidal neurons. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: Long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.

scholarly journals In vivo evidence for the unique kinetics of evoked dopamine release in the patch and matrix compartments of the striatum

2021 ◽  
Author(s):  
Andrea Jaquins-Gerstl ◽  
Kathryn M. Nesbitt ◽  
Adrian C. Michael
Keyword(s):  
Dopamine Release ◽  
Spatial Organization ◽  
Dorsal Striatum ◽  
Immunohistochemical Analysis ◽  
Extensive Literature ◽  
Fast Scan Cyclic Voltammetry ◽  
Medial Dorsal ◽  
The Matrix ◽  
Slow Kinetic

AbstractThe neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson’s disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance. Graphical abstract

scholarly journals Statistical Comparison of Spike Responses to Natural Stimuli in Monkey Area V1 With Simulated Responses of a Detailed Laminar Network Model for a Patch of V1

2011 ◽  
Vol 105 (2) ◽  
pp. 757-778 ◽  
Author(s):  
Malte J. Rasch ◽  
Klaus Schuch ◽  
Nikos K. Logothetis ◽  
Wolfgang Maass
Keyword(s):  
Network Model ◽  
Network Models ◽  
Cortical Network ◽  
Inhibitory Neurons ◽  
Sensory Stimuli ◽  
Natural Stimuli ◽  
Cortical Areas ◽  
Model Response ◽  
Spiking Activity

A major goal of computational neuroscience is the creation of computer models for cortical areas whose response to sensory stimuli resembles that of cortical areas in vivo in important aspects. It is seldom considered whether the simulated spiking activity is realistic (in a statistical sense) in response to natural stimuli. Because certain statistical properties of spike responses were suggested to facilitate computations in the cortex, acquiring a realistic firing regimen in cortical network models might be a prerequisite for analyzing their computational functions. We present a characterization and comparison of the statistical response properties of the primary visual cortex (V1) in vivo and in silico in response to natural stimuli. We recorded from multiple electrodes in area V1 of 4 macaque monkeys and developed a large state-of-the-art network model for a 5 × 5-mm patch of V1 composed of 35,000 neurons and 3.9 million synapses that integrates previously published anatomical and physiological details. By quantitative comparison of the model response to the “statistical fingerprint” of responses in vivo, we find that our model for a patch of V1 responds to the same movie in a way which matches the statistical structure of the recorded data surprisingly well. The deviation between the firing regimen of the model and the in vivo data are on the same level as deviations among monkeys and sessions. This suggests that, despite strong simplifications and abstractions of cortical network models, they are nevertheless capable of generating realistic spiking activity. To reach a realistic firing state, it was not only necessary to include both N -methyl-d-aspartate and GABAB synaptic conductances in our model, but also to markedly increase the strength of excitatory synapses onto inhibitory neurons (>2-fold) in comparison to literature values, hinting at the importance to carefully adjust the effect of inhibition for achieving realistic dynamics in current network models.

scholarly journals From blastocyst to gastrula: gene regulatory networks of embryonic stem cells and early mouse embryogenesis

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130542 ◽  
Author(s):  
David-Emlyn Parfitt ◽  
Michael M. Shen
Keyword(s):  
Stem Cells ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Network Models ◽  
Cell Types ◽  
Mammalian Development ◽  
A Genome

To date, many regulatory genes and signalling events coordinating mammalian development from blastocyst to gastrulation stages have been identified by mutational analyses and reverse-genetic approaches, typically on a gene-by-gene basis. More recent studies have applied bioinformatic approaches to generate regulatory network models of gene interactions on a genome-wide scale. Such models have provided insights into the gene networks regulating pluripotency in embryonic and epiblast stem cells, as well as cell-lineage determination in vivo . Here, we review how regulatory networks constructed for different stem cell types relate to corresponding networks in vivo and provide insights into understanding the molecular regulation of the blastocyst–gastrula transition.

scholarly journals Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrei Vovk ◽  
Chad Gu ◽  
Michael G Opferman ◽  
Larisa E Kapinos ◽  
Roderick YH Lim ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Intrinsically Disordered Proteins ◽  
Nucleocytoplasmic Transport ◽  
Transport Proteins ◽  
Disordered Proteins ◽  
Biophysical Model ◽  
Nuclear Pore ◽  
Intrinsically Disordered

Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function.

scholarly journals Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Aaron Benson Wong ◽  
J Gerard G Borst
Keyword(s):  
Inferior Colliculus ◽  
Spatial Organization ◽  
Functional Organization ◽  
Frequency Tuning ◽  
Gabaergic Neurons ◽  
Two Photon ◽  
Spontaneous Movements ◽  
Multimodal Information ◽  
Auditory Organization

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

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