Genetic strategies to access activated neurons

DeNardo, Laura A; Luo, Liqun

doi:10.1016/j.conb.2017.05.014

Cited by 126 publications

(92 citation statements)

References 70 publications

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“…The questions about the ongoing reorganization and recruitment of neurons into the LTM engram is indeed highly debated 45,46 . In recent years, the combination of transgenics and optogenetics has allowed neuroscientists to identify memory engram cells by detecting and tagging specific populations of cells that are active during different learning phases 5 . In agreement with our results, one recent study found an activation of neurons in the prelimbic cortex during the retrieval of fear memory in mice in addition to those neurons active during stimulus presentation or early memory recalls 47 .…”

Section: Discussionmentioning

confidence: 99%

“…Genetic approaches, including immediate early gene-based strategies to tag cells in an activity-dependent manner, have clearly advanced our understanding how neural activity underlies behaviour 5 . However, many of the current methods require fixed tissue to visualize previously active neurons and are therefore inadequate to follow fast temporal dynamics of activity patterns.…”

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confidence: 99%

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In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata

Delestro

Scheunemann

Pedrazzani

et al. 2020

Sci Rep

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How does the concerted activity of neuronal populations shape behavior? impediments to address this question are primarily due to critical experimental barriers. An integrated perspective on large scale neural information processing requires an in vivo approach that can combine the advantages of exhaustively observing all neurons dedicated to a given type of stimulus, and simultaneously achieve a resolution that is precise enough to capture individual neuron activity. current experimental data from in vivo observations are either restricted to a small fraction of the total number of neurons, or are based on larger brain volumes but at a low spatial and temporal resolution. Consequently, fundamental questions as to how sensory information is represented on a population scale remain unanswered. in Drosophila melanogaster, the mushroom body (MB) represents an excellent model to analyze sensory coding and memory plasticity. In this work, we present an experimental setup coupled with a dedicated computational method that provides in vivo measurements of the activity of hundreds of densely packed somata uniformly spread in the MB. We exploit spinning-disk confocal 3D imaging over time of the whole MB cell body layer in vivo while it is exposed to olfactory stimulation. Importantly, to derive individual signal from densely packed somata, we have developed a fully automated image analysis procedure that takes advantage of the specificities of our data. After anisotropy correction, our approach operates a dedicated spot detection and registration over the entire time sequence to transform trajectories to identifiable clusters. This enabled us to discard spurious detections and reconstruct missing ones in a robust way. We demonstrate that this approach outperformed existing methods in this specific context and made possible high-throughput analysis of approximately 500 single somata uniformly spread over the MB in various conditions. Applying this approach, we find that learned experiences change the population code of odor representations in the MB. After long-term memory (LTM) formation, we quantified an increase in responsive somata count and a stable single neuron signal. We predict that this method, which should further enable studying the population pattern of neuronal activity, has the potential to uncover fine details of sensory processing and memory plasticity.All behavior relies on accurate information processing of sensory signals carried out by the concerted activity of populations of neurons 1,2 . While much is known about the pathways of neuronal transduction, how the integration of information derives from the cooperative action of neuronal activity remains largely elusive. However, for many functions of the brain such as sensory processing or memory plasticity, the important coding might be represented within the neuronal population rather than the individual cell. In animal models, recent developments in the field of in vivo imaging tools have allowed neuroscientists to characterize neuronal activity patte...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata

Delestro

Scheunemann

Pedrazzani

et al. 2020

Sci Rep

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“…Genetic access of activated neurons has emerged as an important tool to dissect neural circuit function (40). Using TRAP2 (25), we show that the physiological imbalance following water deprivation produces a motivational drive encoded in the activity of a molecularly defined neuronal type within hypothalamic MnPO.…”

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confidence: 99%

Thirst-associated preoptic neurons encode an aversive motivational drive

Allen

DeNardo

Chen

et al. 2017

Science

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268

256

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Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency. This stimulation was aversive, and instrumentally pausing stimulation could reinforce lever-pressing. Activity of these neurons gradually decreased over the course of an operant session. Thus, the activity of dehydration-activated MnPO neurons establishes a scalable, persistent, and aversive internal state that dynamically controls thirst-motivated behavior.

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“…In the last decade, groundbreaking technological advances have allowed neuroscientists to take control of neural firing with impressive precision and specificity ( Figure 1) (4 -7). An in-depth description of these tools is outside the scope of this paper [see (4)(5)(6)(7)(8) for comprehensive descriptions]. Concisely, two techniques have fundamentally changed the landscape of neural circuit dissection: optogenetics, which controls neuronal firing with light, and chemogenetics, which alters neuronal firing with otherwise biologically inert compounds.…”

Section: The Era Of Circuit Mappingmentioning

confidence: 99%

MouseCircuits.org: An online repository to guide the circuit era of disordered affect

Anderson¹,

Dumitriu²

2020

Preprint

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Affective disorders rank amongst the most disruptive and prevalent psychiatric diseases, resulting in enormous societal and economic burden, and immeasurable personal costs. Novel therapies are urgently needed but have remained elusive. The era of circuit-mapping in rodent models of disordered affect, ushered in by recent technological advancements allowing for precise and specific neural control, has reenergized the hope for precision psychiatry. Here, we present a novel whole-brain cumulative network and critically access the progress made todate on circuits mediating affective-like behaviors in rodents to seek unifying principles of this cumulative data. We identified 106 original manuscripts in which optogenetics or chemogenetics were used to dissect behaviors related to fear-like, depressive-like or anxiety-like behaviors in rodents. Focusing on the 60 manuscripts that investigated pathways rather than regions, we identified emergent themes. We found that while a few pathways have been validated across similar behaviors and multiple labs, the data is mostly disjointed, with evidence of bidirectional effects of several pathways. Additionally, there is a need for analysis informed by observation prior to perturbation. Given the complex nature of brain connectivity, we argue that the compartmentalized viewpoint that develops as a consequence of fragmented pathway-specific manipulations does not readily lend itself to an integrative picture. To address this, we launched an interactive online consortium, MouseCircuits.org, an open-source platform for consolidated circuit data. This tool aims to support the shared vision of informed circuit dissection that ultimately leads to prevention and treatment of human disorders.

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Genetic strategies to access activated neurons

Cited by 126 publications

References 70 publications

In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata

In vivo large-scale analysis of Drosophila neuronal calcium traces by automated tracking of single somata

Thirst-associated preoptic neurons encode an aversive motivational drive

MouseCircuits.org: An online repository to guide the circuit era of disordered affect

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