Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons

Abstract

Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in cerebellar stellate cells (SCs), 3D-reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that, during development, synaptic strength was homogeneously reduced along the somato-dendritic axis, but that dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits.