scholarly journals NeuroGFX: a graphical functional explorer for fruit fly brain circuits

2016 ◽  
Author(s):  
Chung-Heng Yeh ◽  
Yiyin Zhou ◽  
Nikul H. Ukani ◽  
Aurel A. Lazar
Keyword(s):  
Computational Modeling ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Graphical Interface ◽  
Biological Structure ◽  
Levels Of Abstraction ◽  
Whole Brain ◽  
Brain Circuits ◽  
Circuit Structure

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.

scholarly journals The Drosophila Larval Locomotor Circuit Provides a Model to Understand Neural Circuit Development and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Iain Hunter ◽  
Bramwell Coulson ◽  
Aref Arzan Zarin ◽  
Richard A. Baines
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Model Organisms ◽  
Generic Model ◽  
Critical Periods ◽  
Neuroscience Research ◽  
Circuit Development ◽  
And Function ◽  
Model Circuit

It is difficult to answer important questions in neuroscience, such as: “how do neural circuits generate behaviour?,” because research is limited by the complexity and inaccessibility of the mammalian nervous system. Invertebrate model organisms offer simpler networks that are easier to manipulate. As a result, much of what we know about the development of neural circuits is derived from work in crustaceans, nematode worms and arguably most of all, the fruit fly, Drosophila melanogaster. This review aims to demonstrate the utility of the Drosophila larval locomotor network as a model circuit, to those who do not usually use the fly in their work. This utility is explored first by discussion of the relatively complete connectome associated with one identified interneuron of the locomotor circuit, A27h, and relating it to similar circuits in mammals. Next, it is developed by examining its application to study two important areas of neuroscience research: critical periods of development and interindividual variability in neural circuits. In summary, this article highlights the potential to use the larval locomotor network as a “generic” model circuit, to provide insight into mammalian circuit development and function.

scholarly journals Targeted manipulation of neuronal activity in behaving adult flies

2016 ◽  
Author(s):  
Stefanie Hampel ◽  
Andrew Michael Seeds
Keyword(s):  
Drosophila Melanogaster ◽  
Neuronal Activity ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Specific Behavior ◽  
Freely Behaving ◽  
The Rich ◽  
Circuit Function

The ability to control the activity of specific neurons in freely behaving animals provides an effective way to probe the contributions of neural circuits to behavior. Wide interest in studying principles of neural circuit function using the fruit fly Drosophila melanogaster has fueled the construction of an extensive transgenic toolkit for performing such neural manipulations. Here we describe approaches for using these tools to manipulate the activity of specific neurons and assess how those manipulations impact the behavior of flies. We also describe methods for examining connectivity among multiple neurons that together form a neural circuit controlling a specific behavior. This work provides a resource for researchers interested in examining how neurons and neural circuits contribute to the rich repertoire of behaviors performed by flies.

Central Neural Circuits Regulating Maternal Behavior in Nonhuman Mammals

2020 ◽  
pp. 99-163
Author(s):  
Michael Numan
Keyword(s):  
Maternal Behavior ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Virgin Female ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Brain Circuits ◽  
Maternal Motivation ◽  
Maternal Responses ◽  
The Brain

Chapter 5 reviews the brain circuits that regulate maternal behavior in nonhuman mammals. The medial preoptic area (MPOA) is essential for both the onset and maintenance of maternal behavior. Hormones and oxytocin act on the MPOA to stimulate the onset of maternal behavior. The neurotransmitters contained within MPOA neurons that may regulate maternal behavior are described, as are several neural inputs to the MPOA that regulate its output. A defensive neural circuit that inhibits maternal behavior in most virgin female mammals is described. MPOA output stimulates maternal behavior by depressing the defensive circuit while also activating neural circuits that underpin maternal motivation. MPOA output to the mesolimbic dopamine system is essential for appetitive maternal responses, while its output to the periaqueductal gray regulates consummatory responses. Synaptic plasticity within the MPOA-to-mesolimbic DA circuit is involved in the development of an enduring mother–infant bond.

scholarly journals Targeted manipulation of neuronal activity in behaving adult flies

2016 ◽  
Author(s):  
Stefanie Hampel ◽  
Andrew Michael Seeds
Keyword(s):  
Drosophila Melanogaster ◽  
Neuronal Activity ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Specific Behavior ◽  
Freely Behaving ◽  
The Rich ◽  
Circuit Function

The ability to control the activity of specific neurons in freely behaving animals provides an effective way to probe the contributions of neural circuits to behavior. Wide interest in studying principles of neural circuit function using the fruit fly Drosophila melanogaster has fueled the construction of an extensive transgenic toolkit for performing such neural manipulations. Here we describe approaches for using these tools to manipulate the activity of specific neurons and assess how those manipulations impact the behavior of flies. We also describe methods for examining connectivity among multiple neurons that together form a neural circuit controlling a specific behavior. This work provides a resource for researchers interested in examining how neurons and neural circuits contribute to the rich repertoire of behaviors performed by flies.

scholarly journals The Fruit Fly Brain Observatory: from structure to function

2016 ◽  
Author(s):  
Nikul H. Ukani ◽  
Chung-Heng Yeh ◽  
Adam Tomkins ◽  
Yiyin Zhou ◽  
Dorian Florescu ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Structural Data ◽  
Fruit Fly ◽  
Biological Data ◽  
Multiple Sources ◽  
Full Data ◽  
Open Platform ◽  
Brain Circuits ◽  
Brain Data ◽  
High Flexibility

SummaryThe Fruit Fly Brain Observatory (FFBO) is a collaborative effort between experimentalists, theorists and computational neuroscientists at Columbia University, National Tsing Hua University and Sheffield University with the goal to (i) create an open platform for the emulation and biological validation of fruit fly brain models in health and disease, (ii) standardize tools and methods for graphical rendering, representation and manipulation of brain circuits, (iii) standardize tools for representation of fruit fly brain data and its abstractions and support for natural language queries, (iv) create a focus for the neuroscience community with interests in the fruit fly brain and encourage the sharing of fruit fly brain structural data and executable code worldwide. NeuroNLP and NeuroGFX, two key FFBO applications, aim to address two major challenges, respectively: i) seamlessly integrate structural and genetic data from multiple sources that can be intuitively queried, effectively visualized and extensively manipulated, ii) devise executable brain circuit models anchored in structural data for understanding and developing novel hypotheses about brain function. NeuroNLP enables researchers to use plain English (or other languages) to probe biological data that are integrated into a novel database system, called NeuroArch, that we developed for integrating biological and abstract data models of the fruit fly brain. With powerful 3D graphical visualization, NeuroNLP presents a highly accessible portal for the fruit fly brain data. NeuroGFX provides users highly intuitive tools to execute neural circuit models with Neurokernel, an open-source platform for emulating the fruit fly brain, with full data support from the NeuroArch database and visualization support from an interactive graphical interface. Brain circuits can be configured with high flexibility and investigated on multiple levels, e.g., whole brain, neuropil, and local circuit levels. The FFBO is publicly available and accessible at http://fruitflybrain.org from any modern web browsers, including those running on smartphones.

scholarly journals Cre-assisted fine-mapping of neural circuits using orthogonal split inteins

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Haojiang Luan ◽  
Alexander Kuzin ◽  
Ward F Odenwald ◽  
Benjamin H White
Keyword(s):  
Fine Mapping ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Cre Recombinase ◽  
Second Step ◽  
New Approaches ◽  
Brain Circuits

Existing genetic methods of neuronal targeting do not routinely achieve the resolution required for mapping brain circuits. New approaches are thus necessary. Here, we introduce a method for refined neuronal targeting that can be applied iteratively. Restriction achieved at the first step can be further refined in a second step, if necessary. The method relies on first isolating neurons within a targeted group (i.e. Gal4 pattern) according to their developmental lineages, and then intersectionally limiting the number of lineages by selecting only those in which two distinct neuroblast enhancers are active. The neuroblast enhancers drive expression of split Cre recombinase fragments. These are fused to non-interacting pairs of split inteins, which ensure reconstitution of active Cre when all fragments are expressed in the same neuroblast. Active Cre renders all neuroblast-derived cells in a lineage permissive for Gal4 activity. We demonstrate how this system can facilitate neural circuit-mapping in Drosophila.

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
Keyword(s):  
Intensive Care ◽  
Object Recognition ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Synaptic Loss ◽  
Two Photon ◽  
Circuit Structure ◽  
Cortical Synapses ◽  
Behavioral Object

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.

scholarly journals A novel educational module to teach neural circuits for college and high school students: NGSS-neurons, genetics, and selective stimulations

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 117 ◽  
Author(s):  
Zana Majeed ◽  
Felicitas Koch ◽  
Joshua Morgan ◽  
Heidi Anderson ◽  
Jennifer Wilson ◽  
...  
Keyword(s):  
High School ◽  
High School Students ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Neural Pathways ◽  
College Level ◽  
School Students ◽  
Educational Module ◽  
Model Animal

This report introduces various approaches to target defined neural pathways for stimulation and to address the effect of particular neural circuits on behavior in a model animal, the fruit fly (Drosophila melanogaster). The objective of this novel educational module described can be used to explain and address principle concepts in neurobiology for high school and college level students. A goal of neurobiology is to show how neural circuit activity controls corresponding behavior in animals. The fruit fly model system provides powerful genetic tools, such as the UAS-Gal4 system, to manipulate expression of non-native proteins in various populations of defined neurons: glutamergic, serotonergic, GABAergic, and cholinergic. The exhibited behaviors in the examples we provide allows teachers and students to address questions from behaviors to details at a cellular level. We provided example sets of data, obtained in a research lab, as well as ideas on ways to present data for participants and instructors. The optogenetic tool, channelrhodpsin 2 (ChR2), is employed to increase the activity of each population of neurons in a spatiotemporal controlled manner in behaving larvae and adult flies. Various behavioral assays are used to observe the effect of a specific neuron population activation on crawling behavior in larvae and climbing behavior in adult flies. Participants using this module become acquainted with the actions of different neurotransmitters in the nervous system. A pre- and post- assessment survey on the content is provided for teachers, as templates, to address learning of content and concepts.

scholarly journals Targeted manipulation of neuronal activity in behaving adult flies

2016 ◽  
Author(s):  
Stefanie Hampel ◽  
Andrew Michael Seeds
Keyword(s):  
Drosophila Melanogaster ◽  
Neuronal Activity ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Specific Behavior ◽  
Freely Behaving ◽  
The Rich ◽  
Circuit Function

The ability to control the activity of specific neurons in freely behaving animals provides an effective way to probe the contributions of neural circuits to behavior. Wide interest in studying principles of neural circuit function using the fruit fly Drosophila melanogaster has fueled the construction of an extensive transgenic toolkit for performing such neural manipulations. Here we describe approaches for using these tools to manipulate the activity of specific neurons and assess how those manipulations impact the behavior of flies. We also describe methods for examining connectivity among multiple neurons that together form a neural circuit controlling a specific behavior. This work provides a resource for researchers interested in examining how neurons and neural circuits contribute to the rich repertoire of behaviors performed by flies.

scholarly journals Oscillatory integration windows in neurons

2016 ◽  
Author(s):  
Nitin Gupta ◽  
Swikriti Saran Singh ◽  
Mark Stopfer
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Field Potential ◽  
Coincidence Detection ◽  
Uniform Structure ◽  
Detection Mechanism ◽  
Oscillation Frequencies ◽  
Local Field Potential Lfp ◽  
Oscillatory Cycle

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.

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