Mapping the emergence of a subcellular balance between excitatory and inhibitory synapses along dendrites

Abstract

A balance between excitation and inhibition is thought to be important for neurotypical brain function and development. However, how this balance emerges and the spatial scale at which it is established remains largely unknown. We mapped the spatial distribution of synapses along the basal dendrites of developing CA1 pyramidal neurons at four timepoints (P7, P10, P14 and P21) using fibronectin intrabodies (FingRs) targeted against postsynaptic density proteins for both excitatory and inhibitory synapses (PSD95-FingR and GEPH-FingR, respectively (Gross et al., 2013)). Such FingRs were expressed in a sparse subset of individually labelled neurons, delivered by in utero electroporation. We found that excitation and inhibition are tightly correlated at the subcellular level at P7, and this balance is maintained until P14, but is weakened by P21. Furthermore, we observed that excitatory synapses transition from few, large entities which are primarily located on the dendritic shaft at P7, to many smaller entities located primarily on dendritic spines. Inhibitory synapses, on the other hand, emerged as immature structures that lacked an active zone at P7, but otherwise remained mostly constant in number, location, and size throughout development. Together, our data shows that initial neuronal circuits are formed via a set of large excitatory synapses that are located on the dendritic shaft and immature inhibitory synapses, which emerge in a coordinated manner to orchestrate a local excitation/inhibition balance. It is possible that such a subcellular balance is important for maintaining the stability of highly dynamic and plastic networks during early development.

Date of Award	1 Jun 2024
Original language	English
Awarding Institution	King's College London
Supervisor	Juan Burrone (Supervisor) & Robert Hindges (Supervisor)