scholarly journals Convergent energy state-dependent antagonistic signalling by CART and NPY modulates the plasticity of forebrain neurons to regulate feeding in zebrafish

2021 ◽  
Author(s):  
Devika S Bodas ◽  
Aditi Maduskar ◽  
Tarun Kaniganti ◽  
Debia Wakhloo ◽  
Akilandeswari Balasubramanian ◽  
...  

Dynamic re-configuration of circuit function subserves the flexibility of innate behaviours tuned to physiological states. Internal energy stores adaptively regulate feeding-associated behaviours by integrating opposing hunger and satiety signals at the level of neural circuits. Across vertebrate lineages, the neuropeptides CART and NPY have potent anorexic and orexic functions, respectively, and show energy state-dependent expression in interoceptive neurons. However, how the antagonistic activities of these peptides modulate circuit plasticity remain unclear. Using behavioural, neuroanatomical and activity analysis in adult zebrafish, along with pharmacological interventions, we show that CART and NPY activities converge on a population of neurons in the dorsomedial telencephalon (Dm). While CART facilitates glutamatergic neurotransmission at the Dm, NPY dampens the response to glutamate. In energy-rich states, CART enhances NMDA receptor (NMDAR) function by PKA/PKC mediated phosphorylation of the NR1 subunit of the NMDAR complex. Conversely, starvation triggers NPY-mediated reduction in phosphorylated NR1 via calcineurin activation and inhibition of cAMP production leading to reduced responsiveness to glutamate. Our data identify convergent integration of CART and NPY inputs by the Dm neurons to generate nutritional state-dependent circuit plasticity that is correlated with the behavioural switch induced by the opposing actions of satiety and hunger signals.

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160258 ◽  
Author(s):  
Gina G. Turrigiano

It has become widely accepted that homeostatic and Hebbian plasticity mechanisms work hand in glove to refine neural circuit function. Nonetheless, our understanding of how these fundamentally distinct forms of plasticity compliment (and under some circumstances interfere with) each other remains rudimentary. Here, I describe some of the recent progress of the field, as well as some of the deep puzzles that remain. These include unravelling the spatial and temporal scales of different homeostatic and Hebbian mechanisms, determining which aspects of network function are under homeostatic control, and understanding when and how homeostatic and Hebbian mechanisms must be segregated within neural circuits to prevent interference. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.


2018 ◽  
Vol 120 (2) ◽  
pp. 854-866 ◽  
Author(s):  
Sarah E. V. Richards ◽  
Stephen D. Van Hooser

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Fred P Davis ◽  
Aljoscha Nern ◽  
Serge Picard ◽  
Michael B Reiser ◽  
Gerald M Rubin ◽  
...  

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of apparent co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.


2018 ◽  
Vol 115 (42) ◽  
pp. E9926-E9933 ◽  
Author(s):  
Maria Bertuzzi ◽  
Weipang Chang ◽  
Konstantinos Ampatzis

A particularly essential determinant of a neuron’s functionality is its neurotransmitter phenotype. While the prevailing view is that neurotransmitter phenotypes are fixed and determined early during development, a growing body of evidence suggests that neurons retain the ability to switch between different neurotransmitters. However, such changes are considered unlikely in motoneurons due to their crucial functional role in animals’ behavior. Here we describe the expression and dynamics of glutamatergic neurotransmission in the adult zebrafish spinal motoneuron circuit assembly. We demonstrate that part of the fast motoneurons retain the ability to switch their neurotransmitter phenotype under physiological (exercise/training) and pathophysiological (spinal cord injury) conditions to corelease glutamate in the neuromuscular junctions to enhance animals’ motor output. Our findings suggest that motoneuron neurotransmitter switching is an important plasticity-bestowing mechanism in the reconfiguration of spinal circuits that control movements.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Giacomo Limonta ◽  
Annalaura Mancia ◽  
Assja Benkhalqui ◽  
Cristiano Bertolucci ◽  
Luigi Abelli ◽  
...  

Abstract Microplastics have become pervasive environmental pollutants in both freshwater and marine ecosystems. The presence of microplastics have been recorded in the tissues of many wild fish species, and laboratory studies have demonstrated that microplastics can exert adverse health effects. To further investigate the biological mechanisms underlying microplastics toxicity we applied an integrated approach, analyzing the effects of microplastics at transcriptomic, histological and behavioral level. Adult zebrafish have been exposed to two concentrations of high-density polyethylene and polystyrene microplastics for twenty days. Transcriptomic results indicate alterations in the expression of immune system genes and the down-regulation of genes correlated with epithelium integrity and lipid metabolism. The transcriptomic findings are supported by tissue alterations and higher occurrence of neutrophils observed in gills and intestinal epithelium. Even the daily rhythm of activity of zebrafish appears to be affected, although the regular pattern of activity is recovered over time. Considering the transcriptomic and histological findings reported, we hypothesize that the effects on mucosal epithelium integrity and immune response could potentially reduce the organism defense against pathogens, and lead to a different utilization of energy stores.


2016 ◽  
Author(s):  
Stefanie Hampel ◽  
Andrew Michael Seeds

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.


2021 ◽  
Vol 15 ◽  
Author(s):  
Ou Fu ◽  
Yasuhiko Minokoshi ◽  
Ken-ichiro Nakajima

Feeding is essential for survival and taste greatly influences our feeding behaviors. Palatable tastes such as sweet trigger feeding as a symbol of a calorie-rich diet containing sugar or proteins, while unpalatable tastes such as bitter terminate further consumption as a warning against ingestion of harmful substances. Therefore, taste is considered a criterion to distinguish whether food is edible. However, perception of taste is also modulated by physiological changes associated with internal states such as hunger or satiety. Empirically, during hunger state, humans find ordinary food more attractive and feel less aversion to food they usually dislike. Although functional magnetic resonance imaging studies performed in primates and in humans have indicated that some brain areas show state-dependent response to tastes, the mechanisms of how the brain senses tastes during different internal states are poorly understood. Recently, using newly developed molecular and genetic tools as well as in vivo imaging, researchers have identified many specific neuronal populations or neural circuits regulating feeding behaviors and taste perception process in the central nervous system. These studies could help us understand the interplay between homeostatic regulation of energy and taste perception to guide proper feeding behaviors.


2017 ◽  
Author(s):  
Dan Landayan ◽  
David S. Feldman ◽  
Fred W. Wolf

Hunger evokes stereotypic behaviors that favor the discovery of nutrients. The neural pathways that coordinate internal and external cues to motivate food seeking behaviors are only partly known. Drosophila that are food deprived increase locomotor activity, are more efficient in locating a discrete source of nutrition, and are willing to overcome adversity to obtain food. Here we developed a semi-naturalistic assay and show that two distinct dopaminergic neural circuits regulate food-seeking behaviors. One group, the PAM neurons, functions in food deprived flies while the other functions in well fed flies, and both promote food seeking. These satiation state-dependent circuits converge on dopamine D1 receptor-expressing Kenyon cells of the mushroom body, where neural activity promotes food seeking behavior independent of satiation state. These findings provide evidence for active food seeking in well-fed flies that is separable from hunger-driven seeking.


2020 ◽  
Author(s):  
Ju Yang ◽  
Nicola Mandriota ◽  
Steven Glenn Harrellson ◽  
John Anthony Jones-Molina ◽  
Rafael Yuste ◽  
...  

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.


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