Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development

Sally Horton; Vincenzo Mastrolia; Rachel E. Jackson; Sarah Kemlo; Pedro M. Pereira Machado; Maria Alejandra Carbajal; Robert Hindges; Roland A. Fleck; Paulo Aguiar; Guilherme Neves; Juan Burrone

doi:10.1016/j.celrep.2024.114361

Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development

Sally Horton, Vincenzo Mastrolia, Rachel E. Jackson, Sarah Kemlo, Pedro M. Pereira Machado, Maria Alejandra Carbajal, Robert Hindges, Roland A. Fleck, Paulo Aguiar, Guilherme Neves^*, Juan Burrone^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 μm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.

Original language	English
Article number	114361
Journal	Cell Reports
Volume	43
Issue number	7
Early online date	18 Jun 2024
DOIs	https://doi.org/10.1016/j.celrep.2024.114361
Publication status	Published - 23 Jul 2024

Keywords

CP: Neuroscience
dendrites
dendritic integration
E-I balance
hippocampus
neurodevelopment
synapse development
synapse formation

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title = "Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development",

abstract = "Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 μm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.",

keywords = "CP: Neuroscience, dendrites, dendritic integration, E-I balance, hippocampus, neurodevelopment, synapse development, synapse formation",

author = "Sally Horton and Vincenzo Mastrolia and Jackson, {Rachel E.} and Sarah Kemlo and {Pereira Machado}, {Pedro M.} and Carbajal, {Maria Alejandra} and Robert Hindges and Fleck, {Roland A.} and Paulo Aguiar and Guilherme Neves and Juan Burrone",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

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doi = "10.1016/j.celrep.2024.114361",

language = "English",

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T1 - Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development

AU - Horton, Sally

AU - Mastrolia, Vincenzo

AU - Jackson, Rachel E.

AU - Kemlo, Sarah

AU - Pereira Machado, Pedro M.

AU - Carbajal, Maria Alejandra

AU - Hindges, Robert

AU - Fleck, Roland A.

AU - Aguiar, Paulo

AU - Neves, Guilherme

AU - Burrone, Juan

PY - 2024/7/23

Y1 - 2024/7/23

N2 - Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 μm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.

AB - Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 μm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.

KW - CP: Neuroscience

KW - dendrites

KW - dendritic integration

KW - E-I balance

KW - hippocampus

KW - neurodevelopment

KW - synapse development

KW - synapse formation

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DO - 10.1016/j.celrep.2024.114361

M3 - Article

AN - SCOPUS:85196183410

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 114361

ER -

Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development

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Keywords

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