scholarly journals Prolonged anesthesia alters brain synaptic architecture

2021 ◽  
Vol 118 (7) ◽  
pp. e2023676118
Author(s):  
Michael Wenzel ◽  
Alexander Leunig ◽  
Shuting Han ◽  
Darcy S. Peterka ◽  
Rafael Yuste

Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding ∼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.

2019 ◽  
Author(s):  
Michael Wenzel ◽  
Alexander Leunig ◽  
Shuting Han ◽  
Darcy S. Peterka ◽  
Rafael Yuste

SUMMARYProlonged medically-induced coma (pMIC), a procedure performed in millions of patients worldwide, leads to cognitive impairment, yet the underlying brain mechanism remains unknown. No experimental studies of medically-induced coma (MIC) exceeding ~6 hours exist. For MIC of less than 6 hours, studies in developing rodents have documented transient changes of cortical synapse formation. However, in adulthood, cortical synapses are thought to become stabilized. Here, we establish pMIC (up to 24 hrs) in adolescent and mature mice, and combine repeated behavioral object recognition assessments with longitudinal two-photon imaging of cortical synapses. We find that pMIC affects cognitive function, and is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the post-anesthetic period is dominated by synaptic loss. These results carry profound implications for intensive medical care, as they point out at significant structural side effects of pMIC on cortical brain synaptic architecture across age levels.


2021 ◽  
Author(s):  
Lloyd E. Russell ◽  
Henry W.P. Dalgleish ◽  
Rebecca Nutbrown ◽  
Oliver Gauld ◽  
Dustin Herrmann ◽  
...  

Recent advances combining two-photon calcium imaging and two-photon optogenetics with digital holography now allow us to read and write neural activity in vivo at cellular resolution with millisecond temporal precision. Such 'all-optical' techniques enable experimenters to probe the impact of functionally defined neurons on neural circuit function and behavioural output with new levels of precision. This protocol describes the experimental strategy and workflow for successful completion of typical all-optical interrogation experiments in awake, behaving head-fixed mice. We describe modular procedures for the setup and calibration of an all-optical system, the preparation of an indicator and opsin-expressing and task-performing animal, the characterization of functional and photostimulation responses and the design and implementation of an all-optical experiment. We discuss optimizations for efficiently selecting and targeting neuronal ensembles for photostimulation sequences, as well as generating photostimulation response maps from the imaging data that can be used to examine the impact of photostimulation on the local circuit. We demonstrate the utility of this strategy using all-optical experiments in three different brain areas - barrel cortex, visual cortex and hippocampus - using different experimental setups. This approach can in principle be adapted to any brain area for all-optical interrogation experiments to probe functional connectivity in neural circuits and for investigating the relationship between neural circuit activity and behaviour.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2574
Author(s):  
Emily S. Wilson ◽  
Karen Litwa

The hyaluronan-based extracellular matrix is expressed throughout nervous system development and is well-known for the formation of perineuronal nets around inhibitory interneurons. Since perineuronal nets form postnatally, the role of hyaluronan in the initial formation of neural circuits remains unclear. Neural circuits emerge from the coordinated electrochemical signaling of excitatory and inhibitory synapses. Hyaluronan localizes to the synaptic cleft of developing excitatory synapses in both human cortical spheroids and the neonatal mouse brain and is diminished in the adult mouse brain. Given this developmental-specific synaptic localization, we sought to determine the mechanisms that regulate hyaluronan synthesis and signaling during synapse formation. We demonstrate that hyaluronan synthase-2, HAS2, is sufficient to increase hyaluronan levels in developing neural circuits of human cortical spheroids. This increased hyaluronan production reduces excitatory synaptogenesis, promotes inhibitory synaptogenesis, and suppresses action potential formation. The hyaluronan receptor, CD44, promotes hyaluronan retention and suppresses excitatory synaptogenesis through regulation of RhoGTPase signaling. Our results reveal mechanisms of hyaluronan synthesis, retention, and signaling in developing neural circuits, shedding light on how disease-associated hyaluronan alterations can contribute to synaptic defects.


2016 ◽  
Author(s):  
Chung-Heng Yeh ◽  
Yiyin Zhou ◽  
Nikul H. Ukani ◽  
Aurel A. Lazar

SummaryRecently, multiple focused efforts have resulted in substantial increase in the availability of connectome data in the fruit fly brain. Elucidating neural circuit function from such structural data calls for a scalable computational modeling methodology. We propose such a methodology that includes i) a brain emulation engine, with an architecture that can tackle the complexity of whole brain modeling, ii) a database that supports tight integration of biological and modeling data along with support for domain specific queries and circuit transformations, and iii) a graphical interface that allows for total flexibility in configuring neural circuits and visualizing run-time results, both anchored on model abstractions closely reflecting biological structure. Towards the realization of such a methodology, we have developed NeuroGFX and integrated it into the architecture of the Fruit Fly Brain Observatory (http://fruitflybrain.org). The computational infrastructure in NeuroGFX is provided by Neurokernel, an open source platform for the emulation of the fruit fly brain, and NeuroArch, a database for querying and executing fruit fly brain circuits. The integration of the two enables the algorithmic construction/manipulation/revision of executable circuits on multiple levels of abstraction of the same model organism. The power of this computational infrastructure can be leveraged through an intuitive graphical interface that allows visualizing execution results in the context of biological structure. This provides an environment where computational researchers can present configurable, executable neural circuits, and experimental scientists can easily explore circuit structure and function ultimately leading to biological validation. With these capabilities, NeuroGFX enables the exploration of function from circuit structure at whole brain, neuropil, and local circuit level of abstraction. By allowing for independently developed models to be integrated at the architectural level, NeuroGFX provides an open plug and play, collaborative environment for whole brain computational modeling of the fruit fly.


2016 ◽  
Author(s):  
Nitin Gupta ◽  
Swikriti Saran Singh ◽  
Mark Stopfer

AbstractOscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly tested this idea in the locust olfactory system. We found that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we found that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrated that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.


Author(s):  
Samantha Hughes ◽  
Tansu Celikel

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.


2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.


Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 589-597 ◽  
Author(s):  
M. Hoshino ◽  
E. Suzuki ◽  
Y. Nabeshima ◽  
C. Hama

The development of neural circuits is regulated by a large number of factors that are localized at distinct neural sites. We report here the localization of one of these factors, hikaru genki (hig) protein, at synaptic clefts in the pupal and adult nervous systems of Drosophila. In hig mutants, unusually frequent bursting activity of the muscles and abnormal motor behavior during the adult stage suggest the misfunction of neuromuscular circuitry. Our immunohistochemical analyses revealed that hig protein, produced by neurons, is secreted from the presynaptic terminals into the spaces between the presynaptic and postsynaptic terminals. In addition, we have found that the localization of this protein in the synaptic spaces temporally correlates with its functional requirement during a critical period that occurs in the middle stage of pupal formation, a period when a number of dendrite and axon growth cones meet to form synapses. These findings indicate that hig protein functions in the formation of functional neural circuits from the early stages of synapse formation.


Author(s):  
Rinat Galiautdinov

The chapter describes the new approach in artificial intelligence based on simulated biological neurons and creation of the neural circuits for the sphere of IoT which represent the next generation of artificial intelligence and IoT. Unlike existing technical devices for implementing a neuron based on classical nodes oriented to binary processing, the proposed path is based on simulation of biological neurons, creation of biologically close neural circuits where every device will implement the function of either a sensor or a “muscle” in the frame of the home-based live AI and IoT. The research demonstrates the developed nervous circuit constructor and its usage in building of the AI (neural circuit) for IoT.


2018 ◽  
Vol 62 (11-12) ◽  
pp. 807-818 ◽  
Author(s):  
Françoise Gofflot ◽  
Benoit Lizen

Neural circuit formation requires the intricate orchestration of multiple developmental events including cell fate specification, cell migration, axon guidance, dendritic growth, synaptic target selection, and synaptogenesis. The HOX proteins are well-known transcriptional regulators that control embryonic development. Investigations into their action in the vertebrate central nervous system have demonstrated pivotal roles in specifying neural subpopulations, but also in several successive steps required for the assembly of neuronal circuitry, such as neuron migration, axon growth and pathfinding and synaptic target selection. Several lines of evidence suggest that the HOX transcription factors could also regulate synaptogenesis processes even after the process of axonal and dendritic guidance has concluded. Here we will review the current data on HOX proteins in neural circuit formation in order to evaluate their potential roles in establishing neuronal connectivity with specific emphasis on synapse formation and maturation.


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