Abstract

Biological and artificial neural networks learn by modifying synaptic weights, but it is unclear how these systems can retain previous knowledge and also acquire new information. Here we show that cortical pyramidal neurons can solve this plasticity-versus-stability dilemma by differentially regulating synaptic plasticity at distinct dendritic compartments. Oblique dendrites of adult mouse layer 5b cortical pyramidal neurons selectively received monosynaptic thalamic input, integrated linearly, and-- surprisingly--lacked synaptic potentiation. In contrast, basal dendrites, which do not receive thalamic input, exhibited conventional NMDA receptor-mediated supralinear integration and synaptic potentiation. Congruently, spiny synapses on oblique branches showed low structural plasticity in vivo. A selective decline in NMDAR activity and expression at synapses on oblique dendrites was controlled by an experience-dependent critical period. Our results demonstrate a new biological mechanism for how single neurons can safeguard a set of inputs from ongoing plasticity by altering synaptic properties at distinct dendritic domains.