scholarly journals Inserting new synaptic connections into damaged neural circuits: towards synapse therapy?

2022 ◽  
Vol 17 (2) ◽  
pp. 300
Author(s):  
Ithai Rabinowitch
Neuroforum ◽  
2018 ◽  
Vol 24 (2) ◽  
pp. A53-A60
Author(s):  
Johannes Felsenberg ◽  
David Owald

Abstract Stimulus directed behavior is regulated by communication between neurons within neural circuits throughout an animal’s brain. Experience can change the dynamics of neural circuits by modifying specific synaptic connections. However, pinpointing the sites of behavioral-relevant plasticity has proven challenging. Technical advances in controlling and monitoring neural activity in behaving animals have allowed for marked progress in understanding the logic underlying learning and memory in the model system Drosophila melanogaster. The fruit fly has a numerically simple brain and probing identified network components has become feasible. Here, we discuss cellular and circuit mechanisms underlying associative learning. We also provide insights into the computational operations encoding associative memories in the fly. Beyond their roles in learning and memory retrieval, these circuit components are recruited for the reevaluation of memories during memory extinction and reconsolidation.


2017 ◽  
Vol 114 (29) ◽  
pp. 7505-7512 ◽  
Author(s):  
Bing Wu ◽  
Jiefu Li ◽  
Ya-Hui Chou ◽  
David Luginbuhl ◽  
Liqun Luo

The formation of complex but highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information-processing channel. Each compartment is separated from the adjacent compartments by membranous processes from ensheathing glia. Here we show that Thisbe, an FGF released from olfactory neurons, particularly from local interneurons, instructs ensheathing glia to wrap each glomerulus. The Heartless FGF receptor acts cell-autonomously in ensheathing glia to regulate process extension so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes overwrapping of the glomeruli their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation.


2017 ◽  
Author(s):  
Yusuke Hirabayashi ◽  
Juan Carlos Tapia ◽  
Franck Polleux

A challenging aspect of neuroscience revolves around mapping the synaptic connections within neural circuits (connectomics) over scales spanning several orders of magnitude (nanometers to meters). Despite significant improvements in serial section electron microscopy (SSEM) technologies, several major roadblocks have impaired its general applicability to mammalian neural circuits. In the present study, we introduce a new approach that circumvents these roadblocks by adapting a genetically-encoded ascorbate peroxidase (APEX2) as a fusion protein to a membrane-targeted fluorescent reporter (CAAX-Venus), and introduce it in single pyramidal neurons in vivo using extremely sparse in utero cortical electroporation (IUCE). This approach allows to perform Correlated Light-SSEM (CoLSSEM) on individual neurons, reconstructing their dendritic and axonal arborization in a targeted way via combination of high-resolution confocal microscopy, and subsequently imaging of its ultrastuctural features and synaptic connections with the ATUM-SEM (automated tape-collecting ultramicrotome - scanning electron microscopy) technology. Our method significantly improves the the feasibility of large-scale reconstructions of neurons within a circuit, and bridges the description of ultrastructural features of genetically-identified neurons with their functional and/or structural connectivity, one of the main goal of connectomics.


Author(s):  
Julia Buhmann ◽  
Arlo Sheridan ◽  
Stephan Gerhard ◽  
Renate Krause ◽  
Tri Nguyen ◽  
...  

AbstractThe study of neural circuits requires the reconstruction of neurons and the identification of synaptic connections between them. To scale the reconstruction to the size of whole-brain datasets, semi-automatic methods are needed to solve those tasks. Here, we present an automatic method for synaptic partner identification in insect brains, which uses convolutional neural networks to identify post-synaptic sites and their pre-synaptic partners. The networks can be trained from human generated point annotations alone and require only simple post-processing to obtain final predictions. We used our method to extract 244 million putative synaptic partners in the fifty-teravoxel full adult fly brain (FAFB) electron microscopy (EM) dataset and evaluated its accuracy on 146,643 synapses from 702 neurons with a total cable length of 312 mm in four different brain regions. The predicted synaptic connections can be used together with a neuron segmentation to infer a connectivity graph with high accuracy: between 92% and 96% of edges linking connected neurons are correctly classified as weakly connected (less than five synapses) and strongly connected (at least five synapses). Our synaptic partner predictions for the FAFB dataset are publicly available, together with a query library allowing automatic retrieval of up- and downstream neurons.


2019 ◽  
pp. 185-188 ◽  
Author(s):  
Denis Zakharov ◽  
Martin Krupa ◽  
Victor Tyutin ◽  
Boris Gutkin

Gamma rhythm plays a key role in a number of cognitive tasks: working memory, sensory processing and routing of information across neural circuits. In comparison with other (lower frequency) oscillations it is sparser and heterogeneous in space. One way to model such properties of gamma rhythm is to describe it through a neural network consisting of interacting populations of pyramidal cells (excitatory neurons) and interneurons (inhibitory neurons), demonstrating cluster synchronization. The structure of such clusters can be modulated by endogenous neuromodulators: dopamine, acetylcholine, adrenaline, etc. In this article we consider the reconfiguring of synchronous clusters of pyramidal interneuron gamma rhythm (pyramidal interneuron gamma, PING) due to the variation of the frequency adaptation parameter of pyramidal cells and the strength of excitatory synaptic connections. We have shown that the variation of the frequency adaptation parameter has the strongest impact on the strongest influence on the cluster structure and can lead to either an increase or a decrease of the number of synchronous clusters.


2014 ◽  
Vol 369 (1654) ◽  
pp. 20130591 ◽  
Author(s):  
Dmitri A. Rusakov ◽  
Alexander E. Dityatev

A growing body of experimental evidence suggests that astroglia, and possibly microglia, play an important part in regulating synaptic networking of the brain. It has also emerged that extracellular matrix (ECM) structures that enwrap synaptic connections can generate molecular signals affecting both neuronal and glial activity. Thus it appears that the mechanism of information processing in the brain, which has hitherto been associated almost exclusively with neural circuits, could also involve informative signal exchange outside the synaptic cleft. In this Theme Issue , research teams including leading experts on astroglia–neuron communication and on ECM signalling report their recent findings, share their views and discuss future conceptual advances in the field. Potential implications for drug development and new therapeutic targets with regard to some common neurological conditions are discussed throughout the issue.


1997 ◽  
Vol 3 (5) ◽  
pp. 295-302 ◽  
Author(s):  
Eve Marder

Circuit dynamics are an outcome of the constant interplay between the intrinsic properties of neurons and the strengths of the synaptic connections among them. Examples from the small networks that generate the rhythms of the crustacean stomatogastric ganglion are used to illustrate general features of the different time scales over which both synaptic and intrinsic properties are altered by circuit activity and neuromodulation. These demonstrate that neither intrinsic membrane properties nor synaptic strengths should be considered fixed parameters; rather, they are dynamic variables with time scales that range from milliseconds to days. NEUROSCIENTIST 3:295–302, 1997


2021 ◽  
Vol 15 ◽  
Author(s):  
Sahar Pourhoseini ◽  
Debalina Goswami-Sewell ◽  
Elizabeth Zuniga-Sanchez

Neural circuit formation is an intricate and complex process where multiple neuron types must come together to form synaptic connections at a precise location and time. How this process is orchestrated during development remains poorly understood. Cell adhesion molecules are known to play a pivotal role in assembling neural circuits. They serve as recognition molecules between corresponding synaptic partners. In this study, we identified a new player in assembling neural circuits in the outer retina, the L1-family cell adhesion molecule Neurofascin (Nfasc). Our data reveals Nfasc is expressed in the synaptic layer where photoreceptors make synaptic connections to their respective partners. A closer examination of Nfasc expression shows high levels of expression in rod bipolars but not in cone bipolars. Disruption of Nfasc using a conditional knockout allele results in selective loss of pre- and post-synaptic proteins in the rod synaptic layer but not in the cone synaptic layer. Electron microscopic analysis confirms that indeed there are abnormal synaptic structures with less dendrites of rod bipolars innervating rod terminals in loss of Nfasc animals. Consistent with these findings, we also observe a decrease in rod-driven retinal responses with disruption of Nfasc function but not in cone-driven responses. Taken together, our data suggest a new role of Nfasc in rod synapses within the mouse outer retina.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Dhruva Raman ◽  
Timothy O'Leary

Synaptic connections in many brain circuits fluctuate, exhibiting substantial turnover and remodelling over hours to days. Surprisingly, experiments show that most of this flux in connectivity persists in the absence of learning or known plasticity signals. How can neural circuits retain learned information despite a large proportion of ongoing and potentially disruptive synaptic changes? We address this question from first principles by analysing how much compensatory plasticity would be required to optimally counteract ongoing fluctuations, regardless of whether fluctuations are random or systematic. Remarkably, we find that the answer is largely independent of plasticity mechanisms and circuit architectures: compensatory plasticity should be at most equal in magnitude to fluctuations, and often less, in direct agreement with previously unexplained experimental observations. Moreover, our analysis shows that a high proportion of learning-independent synaptic change is consistent with plasticity mechanisms that accurately compute error gradients.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


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