scholarly journals Inferring Thalamocortical Monosynaptic Connectivity In-Vivo

2021 ◽  
Author(s):  
Yi Juin Liew ◽  
Aurélie Pala ◽  
Clarissa J Whitmire ◽  
William Andrew Stoy ◽  
Craig R Forest ◽  
...  
Keyword(s):  
Large Scale ◽  
Ex Vivo ◽  
Brain Regions ◽  
Network Activity ◽  
Data Driven ◽  
Synaptic Connectivity ◽  
Homologous Region ◽  
Neural Activation ◽  
Activity Levels

As the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex-vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in-vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in-vivo extracellular single unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal-detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that result in masking of synaptic relationships. Taken together, we provide a framework for establishing­­­ connectivity in multi-site, multi-electrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures.

scholarly journals Inferring Monosynaptic Connectivity Across Brain Structures In-Vivo

2020 ◽  
Author(s):  
Yi Juin Liew ◽  
Aurélie Pala ◽  
Clarissa J Whitmire ◽  
William A Stoy ◽  
Craig R Forest ◽  
...  
Keyword(s):  
Large Scale ◽  
Ex Vivo ◽  
Brain Structures ◽  
Network Activity ◽  
Data Driven ◽  
Synaptic Connectivity ◽  
Homologous Region ◽  
Neural Activation ◽  
And Behavior

Abstract/SummaryAs the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex-vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in-vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in-vivo extracellular single unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal-detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that result in masking of synaptic relationships. Taken together, we provide a framework for establishing connectivity in multi-site, multi-electrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures.New & NoteworthyDespite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.

scholarly journals Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations

2019 ◽  
Vol 130 (6) ◽  
pp. 1049-1063 ◽  
Author(s):  
Logan J. Voss ◽  
Paul S. García ◽  
Harald Hentschke ◽  
Matthew I. Banks
Keyword(s):  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Regions ◽  
Cortical Network ◽  
Network Activity ◽  
Common Mechanism ◽  
General Anesthetics ◽  
Neural Basis

Abstract General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo

2002 ◽  
Vol 20 (5) ◽  
pp. 467-472 ◽  
Author(s):  
Thi My Anh Neildez-Nguyen ◽  
Henri Wajcman ◽  
Michael C. Marden ◽  
Morad Bensidhoum ◽  
Vincent Moncollin ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Large Scale ◽  
Ex Vivo ◽  
Erythroid Cells

Homeostatic Plasticity in the CNS

2019 ◽  
Author(s):  
Peter Wenner ◽  
Pernille Bülow
Keyword(s):  
Homeostatic Plasticity ◽  
Network Activity ◽  
Signaling Cascades ◽  
Neural Function ◽  
Activity Levels ◽  
Membrane Excitability ◽  
Activity Burst ◽  
Intrinsic Plasticity

Homeostatic plasticity refers to a collection of mechanisms that function to homeostatically maintain some feature of neural function. The field began with the view that homeostatic plasticity exists predominantly for the maintenance of spike rate. However, it has become clear that multiple features undergo some form of homeostatic control, including network activity, burst rate, or synaptic strength. There are several different forms of homeostatic plasticity, which are typically triggered following perturbations in activity levels. Homeostatic intrinsic plasticity (HIP) appears to compensate for the perturbation with changes in membrane excitability (voltage-gated conductances); synaptic scaling is thought to be a multiplicative increase or decrease of synaptic strengths throughout the cell following an activity perturbation; presynaptic homeostatic plasticity is a change in probability of release following a perturbation to postsynaptic receptor activity. Each form of homeostatic plasticity can be different in terms of the mechanisms that are engaged, the feature that is homeostatically regulated, the trigger that initiates the compensation, and the signaling cascades that mediate these processes. Homeostatic plasticity is often described in development, but can extend into maturity and has been described in vitro and in vivo.

scholarly journals Large-Scale Chronically Implantable Precision Motorized Microdrive Array for Freely Behaving Animals

2008 ◽  
Vol 100 (4) ◽  
pp. 2430-2440 ◽  
Author(s):  
Jun Yamamoto ◽  
Matthew A. Wilson
Keyword(s):  
Single Unit ◽  
Large Scale ◽  
Neural Circuits ◽  
Brain Regions ◽  
Unit Recording ◽  
Chronic Recording ◽  
Large Numbers ◽  
Freely Behaving

Multiple single-unit recording has become one of the most powerful in vivo electro-physiological techniques for studying neural circuits. The demand has been increasing for small and lightweight chronic recording devices that allow fine adjustments to be made over large numbers of electrodes across multiple brain regions. To achieve this, we developed precision motorized microdrive arrays that use a novel motor multiplexing headstage to dramatically reduce wiring while preserving precision of the microdrive control. Versions of the microdrive array were chronically implanted on both rats (21 microdrives) and mice (7 microdrives), and relatively long-term recordings were taken.

scholarly journals Inference of Synaptic Connectivity and External Variability in Neural Microcircuits

2019 ◽  
Author(s):  
Cody Baker ◽  
Emmanouil Froudarakis ◽  
Dimitri Yatsenko ◽  
Andreas S. Tolias ◽  
Robert Rosenbaum
Keyword(s):  
Functional Connectivity ◽  
Large Scale ◽  
Network Models ◽  
Ground Truth ◽  
External Input ◽  
Synaptic Connectivity ◽  
Imaging Data ◽  
Common Input ◽  
Simplifying Assumptions

AbstractA major goal in neuroscience is to estimate neural connectivity from large scale extracellular recordings of neural activity in vivo. This is challenging in part because any such activity is modulated by the unmeasured external synaptic input to the network, known as the common input problem. Many different measures of functional connectivity have been proposed in the literature, but their direct relationship to synaptic connectivity is often assumed or ignored. For in vivo data, measurements of this relationship would require a knowledge of ground truth connectivity, which is nearly always unavailable. Instead, many studies use in silico simulations as benchmarks for investigation, but such approaches necessarily rely upon a variety of simplifying assumptions about the simulated network and can depend on numerous simulation parameters. We combine neuronal network simulations, mathematical analysis, and calcium imaging data to address the question of when and how functional connectivity, synaptic connectivity, and latent external input variability can be untangled. We show numerically and analytically that, even though the precision matrix of recorded spiking activity does not uniquely determine synaptic connectivity, it is often closely related to synaptic connectivity in practice under various network models. This relation becomes more pronounced when the spatial structure of neuronal variability is considered jointly with precision.

scholarly journals A projection specific logic to sampling visual inputs in mouse superior colliculus

2018 ◽  
Author(s):  
Katja Reinhard ◽  
Chen Li ◽  
Quan Do ◽  
Emily Burke ◽  
Steven Heynderickx ◽  
...  
Keyword(s):  
Superior Colliculus ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Sensory Information ◽  
Cell Types ◽  
Brain Regions ◽  
Visual Response ◽  
Retinal Ganglion ◽  
Parabigeminal Nucleus

AbstractUsing sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.

scholarly journals Selective entrainment of gamma subbands by different slow network oscillations

2017 ◽  
Vol 114 (17) ◽  
pp. 4519-4524 ◽  
Author(s):  
Weiwei Zhong ◽  
Mareva Ciatipis ◽  
Thérèse Wolfenstetter ◽  
Jakob Jessberger ◽  
Carola Müller ◽  
...  
Keyword(s):  
Large Scale ◽  
Dorsal Hippocampus ◽  
Activity Patterns ◽  
Specific Interaction ◽  
Brain Regions ◽  
Network Activity ◽  
Gamma Frequency ◽  
Cornu Ammonis ◽  
Oscillatory Coupling ◽  
Fast Oscillations

Theta oscillations (4–12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30–160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]. We report differential state- and region-specific coupling between the slow large-scale rhythms and superimposed fast oscillations. During awake immobility, all four regions displayed a respiration-entrained rhythm (RR) with decreasing power from OB to CA1, which coupled exclusively to the 80- to 120-Hz gamma subband (γ2). During exploration, when theta activity was prevailing, OB and PLC still showed exclusive coupling of RR with γ2 and no theta-gamma coupling, whereas PAC and CA1 switched to selective coupling of theta with 40- to 80-Hz (γ1) and 120- to 160-Hz (γ3) gamma subbands. Our data illustrate a strong, specific interaction between neuronal activity patterns and respiration. Moreover, our results suggest that the coupling between slow and fast oscillations is a general brain mechanism not limited to the theta rhythm.

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