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
Affiliations
Sally Horton
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK
Vincenzo Mastrolia
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK
Rachel E. Jackson
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK
Sarah Kemlo
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK
Pedro M. Pereira Machado
Centre for Ultrastructural Imaging (CUI), Kings College London, New Hunts House, Guys Hospital Campus, London SE1 1UL, UK
Maria Alejandra Carbajal
Centre for Ultrastructural Imaging (CUI), Kings College London, New Hunts House, Guys Hospital Campus, London SE1 1UL, UK
Robert Hindges
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK
Roland A. Fleck
Centre for Ultrastructural Imaging (CUI), Kings College London, New Hunts House, Guys Hospital Campus, London SE1 1UL, UK
Paulo Aguiar
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
Guilherme Neves
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Corresponding author
Juan Burrone
MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE1 1UL, UK; Corresponding author
Summary: 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.
