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

• Published in: Cell reports (Cambridge) Vol. 43; no. 7; p. 114361
• Main Authors: Horton, Sally, Mastrolia, Vincenzo, Jackson, Rachel E., Kemlo, Sarah, Pereira Machado, Pedro M., Carbajal, Maria Alejandra, Hindges, Robert, Fleck, Roland A., Aguiar, Paulo, Neves, Guilherme, Burrone, Juan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.07.2024; Elsevier
• Subjects: CP: Neuroscience; dendrites; dendritic integration; E-I balance; hippocampus; neurodevelopment; synapse development; synapse formation; dendritic integration; E-I balance; synapse development; hippocampus; neurodevelopment; CP: Neuroscience; dendrites; synapse formation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114361

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. [Display omitted] •Excitatory and inhibitory synapses along CA1 dendrites are spatially correlated•This association is present within short dendritic stretches (<20 μm)•The correlation was highest during early development, greatly declining with maturity•Pioneer inhibitory synapses were structurally correlated but functionally immature Horton et al. reveal a tight correlation in the distribution of excitatory and inhibitory synapses along basal dendrites of developing CA1 hippocampal neurons. This close relationship is strongest in young (P7) neurons, when inhibitory synapses are molecularly and physiologically immature, and decorrelates as the density of excitatory synapses increases.