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 Chromatin Structure and Function in Mosquitoes

2020 ◽  
Vol 11 ◽  
Author(s):  
Óscar M. Lezcano ◽  
Miriam Sánchez-Polo ◽  
José L. Ruiz ◽  
Elena Gómez-Díaz
Keyword(s):  
Drosophila Melanogaster ◽  
Regulatory Networks ◽  
Genome Structure ◽  
Nuclear Architecture ◽  
Model Organism ◽  
Fruit Fly ◽  
Model Organisms ◽  
Epigenetic Mechanisms ◽  
West Nile Fever ◽  
And Function

The principles and function of chromatin and nuclear architecture have been extensively studied in model organisms, such as Drosophila melanogaster. However, little is known about the role of these epigenetic processes in transcriptional regulation in other insects including mosquitoes, which are major disease vectors and a worldwide threat for human health. Some of these life-threatening diseases are malaria, which is caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes; dengue fever, which is caused by an arbovirus mainly transmitted by Aedes aegypti; and West Nile fever, which is caused by an arbovirus transmitted by Culex spp. In this contribution, we review what is known about chromatin-associated mechanisms and the 3D genome structure in various mosquito vectors, including Anopheles, Aedes, and Culex spp. We also discuss the similarities between epigenetic mechanisms in mosquitoes and the model organism Drosophila melanogaster, and advocate that the field could benefit from the cross-application of state-of-the-art functional genomic technologies that are well-developed in the fruit fly. Uncovering the mosquito regulatory genome can lead to the discovery of unique regulatory networks associated with the parasitic life-style of these insects. It is also critical to understand the molecular interactions between the vectors and the pathogens that they transmit, which could hold the key to major breakthroughs on the fight against mosquito-borne diseases. Finally, it is clear that epigenetic mechanisms controlling mosquito environmental plasticity and evolvability are also of utmost importance, particularly in the current context of globalization and climate change.

scholarly journals Drosulfakinin signaling in fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in Drosophila

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shunfan Wu ◽  
Chao Guo ◽  
Huan Zhao ◽  
Mengshi Sun ◽  
Jie Chen ◽  
...  
Keyword(s):  
Sexual Behaviors ◽  
Single Neuron ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neural Substrates ◽  
Internal States ◽  
And Function ◽  
Key Steps ◽  
Male Specific ◽  
Command Center

Abstract Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits. Identifying neural substrates and their molecular modulators promoting or inhibiting animal behaviors are key steps to understand how neural circuits control behaviors. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) that functions at single-neuron resolution to suppress male sexual behavior in Drosophila. We found that Dsk neurons physiologically interact with male-specific P1 neurons, part of a command center for male sexual behaviors, and function oppositely to regulate multiple arousal-related behaviors including sex, sleep and spontaneous walking. We further found that the DSK-2 peptide functions through its receptor CCKLR-17D3 to suppress sexual behaviors in flies. Such a neuropeptide circuit largely overlaps with the fruitless-expressing neural circuit that governs most aspects of male sexual behaviors. Thus DSK/CCKLR signaling in the sex circuitry functions antagonistically with P1 neurons to balance arousal levels and modulate sexual behaviors.

scholarly journals Cytosolic PSD-95 Interactor Alters Functional Organization of Neural Circuits and AMPA Receptor Signaling Independent of PSD-95 Binding

2020 ◽  
pp. 1-72
Author(s):  
Ana R. Rodriguez ◽  
Erin D. Anderson ◽  
Kate M. O’Neill ◽  
Przemyslaw P. McEwan ◽  
Nicholas F. Vigilante ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Microelectrode Array ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Functional Organization ◽  
Protein Localization ◽  
Postsynaptic Density ◽  
Brain Regions ◽  
Receptor Signaling ◽  
And Function

Cytosolic PSD-95 interactor (cypin) regulates many aspects of neuronal development and function, ranging from dendritogenesis to synaptic protein localization. While it is known that removal of postsynaptic density protein-95 (PSD-95) from the postsynaptic density decreases synaptic NMDA receptors and that cypin overexpression protects neurons from NMDA-induced toxicity, little is known about cypin’s role in AMPA receptor clustering and function. Experimental work shows that cypin overexpression decreases PSD-95 levels in synaptosomes and the PSD, decreases PSD-95 clusters/μm2, and increases mEPSC frequency. Analysis of microelectrode array (MEA) data demonstrates that cypin or cypinΔPDZ overexpression increases sensitivity to CNQX and AMPA receptor mediated decreases in spike waveform properties. Network-level analysis of MEA data reveals that cypinΔPDZ overexpression causes networks to be resilient to CNQX-induced changes in local efficiency. Incorporating these findings into a computational model of a neural circuit demonstrates a role for AMPA receptors in cypin-promoted changes to networks and shows that cypin increases firing rate while changing network functional organization, suggesting cypin overexpression facilitates information relay but modifies how information is encoded among brain regions. Our data show that cypin promotes changes to AMPA receptor signaling independent of PSD-95 binding, shaping neural circuits and output to regions beyond the hippocampus.

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 Exosomes regulate neurogenesis and circuit assembly

2019 ◽  
Vol 116 (32) ◽  
pp. 16086-16094 ◽  
Author(s):  
Pranav Sharma ◽  
Pinar Mesci ◽  
Cassiano Carromeu ◽  
Daniel R. McClatchy ◽  
Lucio Schiapparelli ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Neurodevelopmental Disorder ◽  
The Body ◽  
Signaling Networks ◽  
Neuronal Circuit ◽  
Circuit Development ◽  
Neural Cultures ◽  
Neuronal Proliferation

Exosomes are thought to be released by all cells in the body and to be involved in intercellular communication. We tested whether neural exosomes can regulate the development of neural circuits. We show that exosome treatment increases proliferation in developing neural cultures and in vivo in dentate gyrus of P4 mouse brain. We compared the protein cargo and signaling bioactivity of exosomes released by hiPSC-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicates that control exosomes contain multiple functional signaling networks known to be important for neuronal circuit development. Treating MECP2-knockdown human primary neural cultures with control exosomes rescues deficits in neuronal proliferation, differentiation, synaptogenesis, and synchronized firing, whereas exosomes from MECP2-deficient hiPSC neural cultures lack this capability. These data indicate that exosomes carry signaling information required to regulate neural circuit development.

Sensitive Periods in the Development of the Brain and Behavior

2004 ◽  
Vol 16 (8) ◽  
pp. 1412-1425 ◽  
Author(s):  
Eric I. Knudsen
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Critical Role ◽  
Sensitive Period ◽  
Critical Periods ◽  
Sensitive Periods ◽  
Brain And Behavior ◽  
The Individual ◽  
And Behavior ◽  
The Brain

Experience exerts a profound influence on the brain and, therefore, on behavior. When the effect of experience on the brain is particularly strong during a limited period in development, this period is referred to as a sensitive period. Such periods allow experience to instruct neural circuits to process or represent information in a way that is adaptive for the individual. When experience provides information that is essential for normal development and alters performance permanently, such sensitive periods are referred to as critical periods. Although sensitive periods are reflected in behavior, they are actually a property of neural circuits. Mechanisms of plasticity at the circuit level are discussed that have been shown to operate during sensitive periods. A hypothesis is proposed that experience during a sensitive period modifies the architecture of a circuit in fundamental ways, causing certain patterns of connectivity to become highly stable and, therefore, energetically preferred. Plasticity that occurs beyond the end of a sensitive period, which is substantial in many circuits, alters connectivity patterns within the architectural constraints established during the sensitive period. Preferences in a circuit that result from experience during sensitive periods are illustrated graphically as changes in a “stability landscape,” a metaphor that represents the relative contributions of genetic and experiential influences in shaping the information processing capabilities of a neural circuit. By understanding sensitive periods at the circuit level, as well as understanding the relationship between circuit properties and behavior, we gain a deeper insight into the critical role that experience plays in shaping the development of the brain and behavior.

Neurotrophin regulation of neural circuit development and function

2012 ◽  
Vol 14 (1) ◽  
pp. 7-23 ◽  
Author(s):  
Hyungju Park ◽  
Mu-ming Poo
Keyword(s):  
Neural Circuit ◽  
Circuit Development ◽  
And Function

scholarly journals Extreme stiffness of neuronal synapses and implications for synaptic adhesion and plasticity

2020 ◽  
Author(s):  
Ju Yang ◽  
Nicola Mandriota ◽  
Steven Glenn Harrellson ◽  
John Anthony Jones-Molina ◽  
Rafael Yuste ◽  
...  
Keyword(s):  
Structural Changes ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Critical Role ◽  
Theoretical Models ◽  
Cell Types ◽  
Long Term Potentiation ◽  
Biophysical Model ◽  
And Function ◽  
Circuit Function

AbstractSynapses play a critical role in neural circuits, and they are potential sites for learning and memory. Maintenance of synaptic adhesion is critical for neural circuit function, however, biophysical mechanisms that help maintain synaptic adhesion are not clear. Studies with various cell types demonstrated the important role of stiffness in cellular adhesions. Although synaptic stiffness could also play a role in synaptic adhesion, stiffnesses of synapses are difficult to characterize due to their small size and challenges in verifying synapse identity and function. To address these challenges, we have developed an experimental platform that combines atomic force microscopy, fluorescence microscopy, and transmission electron microscopy. Here, using this platform, we report that functional, mature, excitatory synapses had an average elastic modulus of approximately 200 kPa, two orders of magnitude larger than that of the brain tissue, suggesting stiffness might have a role in synapse function. Similar to various functional and anatomical features of neural circuits, synaptic stiffness had a lognormal-like distribution, hinting a possible regulation of stiffness by processes involved in neural circuit function. In further support of this possibility, we observed that synaptic stiffness was correlated with spine size, a quantity known to correlate with synaptic strength. Using established stages of the long-term potentiation timeline and theoretical models of adhesion cluster dynamics, we developed a biophysical model of the synapse that not only explains extreme stiffness of synapses, their statistical distribution, and correlation with spine size, but also offers an explanation to how early biomolecular and structural changes during functional potentiation could lead to strengthening of synaptic adhesion. According to this model, synaptic stiffness serves as an indispensable physical messenger, feeding information back to synaptic adhesion molecules to facilitate maintenance of synaptic adhesion.

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.

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