scholarly journals The synaptic basis of activity-dependent eye-specific competition

2021 ◽  
Author(s):  
Chenghang Zhang ◽  
Colenso M Speer

Binocular vision requires proper developmental wiring of eye-specific inputs to the brain. Axons from the two eyes initially overlap in the dorsal lateral geniculate nucleus and undergo activity-dependent competition to segregate into target domains. The synaptic basis of such refinement is unknown. Here we used volumetric super-resolution imaging to measure the nanoscale molecular reorganization of developing retinogeniculate eye-specific synapses in the mouse brain. The outcome of binocular synaptic competition was determined by the relative eye-specific maturation of presynaptic vesicle content. Genetic disruption of spontaneous retinal activity prevented subsynaptic vesicle pool maturation, recruitment of vesicles to the active zone, synaptic development and eye-specific competition. These results reveal an activity-dependent presynaptic basis for axonal refinement in the mammalian visual system.

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3162
Author(s):  
Maël Duménieu ◽  
Béatrice Marquèze-Pouey ◽  
Michaël Russier ◽  
Dominique Debanne

Visual plasticity is classically considered to occur essentially in the primary and secondary cortical areas. Subcortical visual areas such as the dorsal lateral geniculate nucleus (dLGN) or the superior colliculus (SC) have long been held as basic structures responsible for a stable and defined function. In this model, the dLGN was considered as a relay of visual information travelling from the retina to cortical areas and the SC as a sensory integrator orienting body movements towards visual targets. However, recent findings suggest that both dLGN and SC neurons express functional plasticity, adding unexplored layers of complexity to their previously attributed functions. The existence of neuronal plasticity at the level of visual subcortical areas redefines our approach of the visual system. The aim of this paper is therefore to review the cellular and molecular mechanisms for activity-dependent plasticity of both synaptic transmission and cellular properties in subcortical visual areas.


1994 ◽  
Vol 72 (3) ◽  
pp. 1278-1289 ◽  
Author(s):  
E. Hartveit ◽  
P. Heggelund

1. We studied the degree and source of response variability in different classes of cell in the dorsal lateral geniculate nucleus (dLGN). The response of single cells to a series of contrasts of a stationary flashing light spot was measured. The variability analyses were based on the mean and SD of the response to a number of repeated stimulus presentations. The relative variability was expressed by the coefficient of variation (Cv; SD/mean). 2. At a given contrast, the Cv for lagged cells was larger than for nonlagged cells. No difference was found between the Cv of X and Y cells. The magnitude of the Cv was about the same as previously found for cells in striate cortex. Accordingly, little variability is added at the cortical level. The Cv decreased with increasing contrast showing that the reliability of response and the signal-to-noise ratio was improved with increasing contrast. 3. For some cells, the retinal input was determined by recording S potentials in addition to action potentials. The Cv of the retinal input was smaller than the Cv of the dLGN cells at a given contrast. Thus in the paralyzed and anesthetized preparation, variability was added at the geniculate relay. 4. The additional variability was related to modulatory input from the brain stem. This was shown by comparing Cv versus contrast curves for the dLGN cells obtained during electrical stimulation of the peribrachial region of the brain stem (PBR) with corresponding curves obtained without PBR stimulation. During PBR stimulation, which presumably mimics the effects of arousal on the dLGN cell, the Cv at a given contrast was reduced toward the value for the retinal input to the cell. Furthermore PBR stimulation increased the signal-to-noise-ratio of the cell to the level of the retinal input. 5. When Cv was plotted against response rather than against contrast, approximately the same function was found for the various dLGN cell classes. This indicated that the variability basically depended on firing rate rather than on stimulus contrast. No difference of Cv was seen between lagged and nonlagged cells at a given level of response. The difference found at a given level of contrast reflected differences in firing rate of the two cell classes. During PBR stimulation, there was no clear difference between the Cvs of the dLGN cell and its retinal input at a given level of response.(ABSTRACT TRUNCATED AT 400 WORDS)


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jason C. Sang ◽  
Eric Hidari ◽  
Georg Meisl ◽  
Rohan T. Ranasinghe ◽  
Maria Grazia Spillantini ◽  
...  

AbstractAggregation of α-synuclein (α-syn) is closely linked to Parkinson’s disease (PD) and the related synucleinopathies. Aggregates spread through the brain during the progression of PD, but the mechanism by which this occurs is still not known. One possibility is a self-propagating, templated-seeding mechanism, but this cannot be established without quantitative information about the efficiencies and rates of the key steps in the cellular process. To address this issue, we imaged the uptake and seeding of unlabeled exogenous α-syn fibrils by SH-SY5Y cells and the resulting secreted aggregates, using super-resolution microscopy. Externally-applied fibrils very inefficiently induced self-assembly of endogenous α-syn in a process accelerated by the proteasome. Seeding resulted in the increased secretion of nanoscopic aggregates (mean 35 nm diameter), of both α-syn and Aβ. Our results suggest that cells respond to seed-induced disruption of protein homeostasis predominantly by secreting nanoscopic aggregates; this mechanism may therefore be an important protective response by cells to protein aggregation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tal M. Dankovich ◽  
Rahul Kaushik ◽  
Linda H. M. Olsthoorn ◽  
Gabriel Cassinelli Petersen ◽  
Philipp Emanuel Giro ◽  
...  

AbstractThe brain extracellular matrix (ECM) consists of extremely long-lived proteins that assemble around neurons and synapses, to stabilize them. The ECM is thought to change only rarely, in relation to neuronal plasticity, through ECM proteolysis and renewed protein synthesis. We report here an alternative ECM remodeling mechanism, based on the recycling of ECM molecules. Using multiple ECM labeling and imaging assays, from super-resolution optical imaging to nanoscale secondary ion mass spectrometry, both in culture and in brain slices, we find that a key ECM protein, Tenascin-R, is frequently endocytosed, and later resurfaces, preferentially near synapses. The TNR molecules complete this cycle within ~3 days, in an activity-dependent fashion. Interfering with the recycling process perturbs severely neuronal function, strongly reducing synaptic vesicle exo- and endocytosis. We conclude that the neuronal ECM can be remodeled frequently through mechanisms that involve endocytosis and recycling of ECM proteins.


2009 ◽  
Vol 518 (5) ◽  
pp. 622-635 ◽  
Author(s):  
Martha E. Bickford ◽  
Arkadiusz Slusarczyk ◽  
Emily K. Dilger ◽  
Thomas E. Krahe ◽  
Can Kucuk ◽  
...  

2019 ◽  
Vol 116 (3) ◽  
pp. 304a-305a
Author(s):  
Antoine G. Godin ◽  
Noémie Danné ◽  
Juan A. Varela ◽  
Gao Zhenghong ◽  
Brahim Lounis ◽  
...  

2002 ◽  
Vol 88 (5) ◽  
pp. 2311-2321 ◽  
Author(s):  
Christopher W. Lee ◽  
Stephen J. Eglen ◽  
Rachel O. L. Wong

In many parts of the developing nervous system, the early patterns of connectivity are refined by processes that require neuronal activity. These processes are thought to involve Hebbian mechanisms that lead to strengthening and maintenance of inputs that display correlated pre- and postsynaptic activity and elimination of inputs that fire asynchronously. Here we investigated the role of patterned spontaneous retinal activity and Hebbian synaptic mechanisms on segregation of on and off retinal afferents in the dorsal lateral geniculate nucleus (dLGN) of the developing ferret visual system. We recorded extracellularly the spontaneous spike activity of neighboring pairs of ganglion cells and found thatoff cells have significantly higher mean firing rates thanon cells. Spiking is best correlated between cells of the same sign (on, on; off,off) compared with cells of opposite sign (on,off). We then constructed a simple Hebbian model of retinogeniculate synaptic development based on a correlational framework. Using our recorded activity patterns, together with previous calcium-imaging data, we show that endogenous retinal activity, coupled with Hebbian mechanisms of synaptic development, can drive the segregation of on and off retinal inputs to the dLGN. Segregation occurs robustly when heterosynaptic competition is present within time windows of 50–500 ms. In addition, our results suggest that the initial patterns of connectivity (biases in convergence of inputs) and the strength of inhibition in the network each play a crucial role in determining whether on oroff inputs dominate at maturity.


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