Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function

Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. In this s...

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Main Authors: Dimitar Kostadinov, Joshua R Sanes
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/08964
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author Dimitar Kostadinov
Joshua R Sanes
author_facet Dimitar Kostadinov
Joshua R Sanes
author_sort Dimitar Kostadinov
collection DOAJ
description Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. In this study, we used retinal starburst amacrine cells (SACs), critical components of a direction-selective circuit, to address this issue. In SACs, both processes are mediated by the gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg expression in SACs and recorded from them and their targets, direction-selective ganglion cells (DSGCs). SACs form autapses when self-avoidance is disrupted and fail to form connections with other SACs when self/non-self discrimination is perturbed. Pcdhgs are also required to prune connections between closely spaced SACs. These alterations degrade the direction selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination are essential for proper function of a circuit that computes directional motion.
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spelling doaj.art-8859c39571ff476980a08b9828861e892022-12-22T02:05:27ZengeLife Sciences Publications LtdeLife2050-084X2015-07-01410.7554/eLife.08964Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit functionDimitar Kostadinov0Joshua R Sanes1Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States; Program in Neuroscience, Harvard Medical School, Boston, United StatesCenter for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. In this study, we used retinal starburst amacrine cells (SACs), critical components of a direction-selective circuit, to address this issue. In SACs, both processes are mediated by the gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg expression in SACs and recorded from them and their targets, direction-selective ganglion cells (DSGCs). SACs form autapses when self-avoidance is disrupted and fail to form connections with other SACs when self/non-self discrimination is perturbed. Pcdhgs are also required to prune connections between closely spaced SACs. These alterations degrade the direction selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination are essential for proper function of a circuit that computes directional motion.https://elifesciences.org/articles/08964retinastarburst amacrine cellsynapse eliminationself-recognitiondirection selectivity
spellingShingle Dimitar Kostadinov
Joshua R Sanes
Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
eLife
retina
starburst amacrine cell
synapse elimination
self-recognition
direction selectivity
title Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
title_full Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
title_fullStr Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
title_full_unstemmed Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
title_short Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function
title_sort protocadherin dependent dendritic self avoidance regulates neural connectivity and circuit function
topic retina
starburst amacrine cell
synapse elimination
self-recognition
direction selectivity
url https://elifesciences.org/articles/08964
work_keys_str_mv AT dimitarkostadinov protocadherindependentdendriticselfavoidanceregulatesneuralconnectivityandcircuitfunction
AT joshuarsanes protocadherindependentdendriticselfavoidanceregulatesneuralconnectivityandcircuitfunction