RESUMEN
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.
Asunto(s)
Dendritas , Plasticidad Neuronal , Células Piramidales , Receptores de N-Metil-D-Aspartato , Sinapsis , Animales , Dendritas/metabolismo , Dendritas/fisiología , Sinapsis/metabolismo , Sinapsis/fisiología , Ratones , Receptores de N-Metil-D-Aspartato/metabolismo , Plasticidad Neuronal/fisiología , Células Piramidales/metabolismo , Células Piramidales/fisiología , Ratones Endogámicos C57BL , MasculinoRESUMEN
Recent developments in super-resolution microscopy have revolutionized the study of cell biology. However, dense tissues require exogenous protein expression for single cell morphological contrast. In the nervous system, many cell types and species of interest - particularly human - are not amenable to genetic modification and/or exhibit intricate anatomical specializations which make cellular delineation challenging. Here, we present a method for full morphological labeling of individual neurons from any species or cell type for subsequent cell-resolved protein analysis without genetic modification. Our method, which combines patch-clamp electrophysiology with epitope-preserving magnified analysis of proteome (eMAP), further allows for correlation of physiological properties with subcellular protein expression. We applied Patch2MAP to individual spiny synapses in human cortical pyramidal neurons and demonstrated that electrophysiological AMPA-to-NMDA receptor ratios correspond tightly to respective protein expression levels. Patch2MAP thus permits combined subcellular functional, anatomical, and proteomic analyses of any cell, opening new avenues for direct molecular investigation of the human brain in health and disease.