A dendritic mechanism for balancing synaptic flexibility and stability

Biological and artificial neural networks learn by modifying synaptic weights, but it is unclear how these systems 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 5 cortical pyramidal neurons selectively receive monosynaptic thalamic input, integrate linearly, and lack burst-timing synaptic potentiation. In contrast, basal dendrites, which do not receive thalamic input, exhibit conventional NMDA receptor (NMDAR)-mediated supralinear integration and synaptic potentiation. Congruently, spiny synapses on oblique branches show decreased structural plasticity in vivo. The selective decline in NMDAR activity and expression at synapses on oblique dendrites is controlled by a critical period of visual experience. Our results demonstrate a biological mechanism for how single neurons can safeguard a set of inputs from ongoing plasticity by altering synaptic properties at distinct dendritic domains. [Display omitted] •Highly stable synapses are found in oblique dendrites of L5 PNs in adult mouse V1•Stable synapses receive specific inputs, integrate linearly, and do not strengthen•Oblique dendrite synapses have higher AMPA/NMDA across all spine sizes•Stable synapse properties develop after a critical period of visual experience Yaeger et al. report that neurons in the adult visual cortex organize plastic and stable synapses in discrete dendritic regions. Stable synapses are located in oblique dendrites of layer 5 pyramidal neurons and have distinct physiological properties and protein expression. This mechanism helps protect specific inputs from ongoing experience-dependent plasticity.