scholarly journals Optogenetic Modulation of Intracellular Signalling and Transcription: Focus on Neuronal Plasticity

2017 ◽  
Vol 11 ◽  
pp. 117906951770335 ◽  
Author(s):  
Cyril Eleftheriou ◽  
Fabrizia Cesca ◽  
Luca Maragliano ◽  
Fabio Benfenati ◽  
Jose Fernando Maya-Vetencourt
Keyword(s):  
Temporal Resolution ◽  
Exponential Growth ◽  
Neuronal Plasticity ◽  
Neuronal Networks ◽  
Neural Circuits ◽  
Intracellular Signalling ◽  
Light Stimulation ◽  
Cellular Physiology ◽  
Neuronal Physiology

Several fields in neuroscience have been revolutionized by the advent of optogenetics, a technique that offers the possibility to modulate neuronal physiology in response to light stimulation. This innovative and far-reaching tool provided unprecedented spatial and temporal resolution to explore the activity of neural circuits underlying cognition and behaviour. With an exponential growth in the discovery and synthesis of new photosensitive actuators capable of modulating neuronal networks function, other fields in biology are experiencing a similar re-evolution. Here, we review the various optogenetic toolboxes developed to influence cellular physiology as well as the diverse ways in which these can be engineered to precisely modulate intracellular signalling and transcription. We also explore the processes required to successfully express and stimulate these photo-actuators in vivo before discussing how such tools can enlighten our understanding of neuronal plasticity at the systems level.

scholarly journals Neuronal networks in the spotlight

e-Neuroforum ◽  
2013 ◽  
Vol 19 (2) ◽  
Author(s):  
F. Helmchen ◽  
M. Hübener
Keyword(s):  
Neuronal Networks ◽  
Neural Circuits ◽  
Calcium Influx ◽  
Fluorescent Proteins ◽  
Activity Patterns ◽  
Cell Activity ◽  
Movement Control ◽  
Dynamic Activity ◽  
Two Photon Microscopy

AbstractThe brain’s astounding achievements regard­ing movement control and sensory process­ing are based on complex spatiotemporal ac­tivity patterns in the relevant neuronal net­works. Our understanding of neuronal net­work activity is, however, still poor, not least because of the experimental difficulties in di­rectly observing neural circuits at work in the living brain (in vivo). Over the last decade, new opportunities have emerged-especial­ly utilizing two-photon microscopy-to in­vestigate neuronal networks in action. Cen­tral to this progress was the development of fluorescent proteins that change their emis­sion depending on cell activity, enabling the visualization of dynamic activity patterns in local neuronal populations. Currently, genet­ically encoded calcium indicators, proteins that indicate neuronal activity based on ac­tion potential-evoked calcium influx, are be­ing increasingly used. Long-term expression of these indicators allows repeated moni­toring of the same neurons over weeks and months, such that the stability and plastici­ty of their functional properties can be char­acterized. Furthermore, permanent indicator expression facilitates the correlation of cel­lular activity patterns and behavior in awake animals. Using examples from recent studies of information processing in the mouse neo­cortex, we review in this article these fasci­nating new possibilities and discuss the great potential of the fluorescent proteins to eluci­date the mysteries of neural circuits.

scholarly journals Extracellular matrix supports excitation-inhibition balance in neuronal networks by stabilizing inhibitory synapses

2020 ◽  
Author(s):  
Egor Dzyubenko ◽  
Michael Fleischer ◽  
Daniel Manrique-Castano ◽  
Mina Borbor ◽  
Christoph Kleinschnitz ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Neuronal Network ◽  
Neuronal Plasticity ◽  
Neuronal Networks ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Neuronal Network Activity ◽  
The Brain

AbstractMaintaining the balance between excitation and inhibition is essential for the appropriate control of neuronal network activity. Sustained excitation-inhibition (E-I) balance relies on the orchestrated adjustment of synaptic strength, neuronal activity and network circuitry. While growing evidence indicates that extracellular matrix (ECM) of the brain is a crucial regulator of neuronal excitability and synaptic plasticity, it remains unclear whether and how ECM contributes to neuronal circuit stability. Here we demonstrate that the integrity of ECM supports the maintenance of E-I balance by retaining inhibitory connectivity. Depletion of ECM in mature neuronal networks preferentially decreases the density of inhibitory synapses and the size of individual inhibitory postsynaptic scaffolds. After ECM depletion, inhibitory synapse strength homeostatically increases via the reduction of presynaptic GABAB receptors. However, the inhibitory connectivity reduces to an extent that inhibitory synapse scaling is no longer efficient in controlling neuronal network activity. Our results indicate that the brain ECM preserves the balanced network state by stabilizing inhibitory synapses.Significance statementThe question how the brain’s extracellular matrix (ECM) controls neuronal plasticity and network activity is key for an appropriate understanding of brain functioning. In this study, we demonstrate that ECM depletion much more strongly affects the integrity of inhibitory than excitatory synapses in vitro and in vivo. We revealed that by retaining inhibitory connectivity, ECM ensures the efficiency of inhibitory control over neuronal network activity. Our work significantly expands our current state of knowledge about the mechanisms of neuronal network activity regulation. Our findings are similarly relevant for researchers working on the physiological regulation of neuronal plasticity in vitro and in vivo and for researchers studying the remodeling of neuronal networks upon brain injury, where prominent ECM alterations occur.

scholarly journals Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolette Driscoll ◽  
Richard E. Rosch ◽  
Brendan B. Murphy ◽  
Arian Ashourvan ◽  
Ramya Vishnubhotla ◽  
...  
Keyword(s):  
Temporal Resolution ◽  
Spatial Scales ◽  
Epileptic Seizures ◽  
Therapeutic Interventions ◽  
State Transitions ◽  
Integrated Analysis ◽  
High Temporal Resolution ◽  
Seizure Onset ◽  
Acute Seizures

AbstractNeurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

scholarly journals Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fan Jia ◽  
Li Li ◽  
Haizhou Liu ◽  
Pei Lv ◽  
Xiangwei Shi ◽  
...  
Keyword(s):  
Experimental Data ◽  
Rabies Virus ◽  
Oncolytic Virus ◽  
Neural Circuits ◽  
Bioinformatic Analysis ◽  
Cell Engineering ◽  
Bias Score ◽  
Codon Pair Bias ◽  
Codon Pair

AbstractRabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.

Tracing neural circuits in vivo with Mn-enhanced MRI

2006 ◽  
Vol 24 (4) ◽  
pp. 349-358 ◽  
Author(s):  
Yusuke Murayama ◽  
Bruno Weber ◽  
Kadharbatcha S. Saleem ◽  
Mark Augath ◽  
Nikos K. Logothetis
Keyword(s):  
Neural Circuits ◽  
Enhanced Mri
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