Maturation of a Recurrent Excitatory Neocortical Circuit by Experience-Dependent Unsilencing of Newly Formed Dendritic Spines

SummaryLocal recurrent excitatory circuits are ubiquitous in neocortex, yet little is known about their development or architecture. Here we introduce a quantitative technique for efficient single-cell resolution circuit mapping using 2-photon (2P) glutamate uncaging and analyze experience-dependent neonatal development of the layer 4 barrel cortex local excitatory circuit. We show that sensory experience specifically drives a 3-fold increase in connectivity at postnatal day (P) 9, producing a highly recurrent network. A profound dendritic spinogenesis occurs concurrent with the connectivity increase, but this is not experience dependent. However, in experience-deprived cortex, a much greater proportion of spines lack postsynaptic AMPA receptors (AMPARs) and synaptic connectivity via NMDA receptors (NMDARs) is the same as in normally developing cortex. Thus we describe a approach for quantitative circuit mapping and show that sensory experience sculpts an intrinsically developing template network, which is based on NMDAR-only synapses, by driving AMPARs into newly formed silent spines.

► Photostimulation used to analyze connectivity between individual, identified neurons ► Circuitry and anatomy in layer 4 barrel cortex develop rapidly and concurrently ► Sensory perturbation dissociates functional and anatomical developmental plasticity ► Experience guides circuit maturation by shaping a network that develops intrinsically