Shedding light on how the brain fine-tunes its wiring during learning, a new study finds that different dendritic segments of a single neuron follow distinct rules. The findings challenge the idea that neurons follow a single learning strategy and offer a new perspective on how the brain learns and adapts behavior. The brain's remarkable ability to learn and adapt is rooted in its capacity to modify the connections within its neural circuits – a phenomenon known as synaptic plasticity, in which specific synapses are altered to reshape neural activity and support behavioral change. Neurons, unlike most other cell types, are characterized by their intricate, tree-like dendritic arbors, which extend from the cell body and serve as the primary site for receiving signals from other neurons via synaptic inputs. These dendrites are not uniform; instead, they are organized into distinct compartments with specialized anatomical and biophysical properties which likely influence how various patterns of neural activity trigger the biochemical processes that underlie synaptic plasticity. However, how the brain determines which synapses should be modified during learning and whether individual neurons apply the same plasticity rules uniformly across their structurally and functionally distinct dendritic compartments remains unknown.
To explore how synapses function and adapt during learning, William Wright and colleagues used advanced imaging to observe single synapses in the motor cortex of mice as the animals learned new motor skills. Wright et al. trained mice on a motor task known to drive synaptic plasticity in layer 2/3 motor cortex neurons, observing clear behavioral signs of learning over two weeks. Then, to investigate how individual synapses adapt during this process, Wright et al. used in vivo two-photon imaging with molecular sensors that simultaneously tracked synaptic input (via glutamate release) and neuronal output (via calcium activity). The authors discovered that learning-related patterns of neural activity drive synaptic plasticity differently across dendritic compartments. In apical dendrites, synapses were strengthened when they were coactive with nearby neighbors, suggesting that plasticity here is governed by local interactions between adjacent inputs. In contrast, plasticity in basal dendrites was linked to the neuron's overall output—strengthening or weakening depending on how synapse activity aligned with global action potential firing. Suppressing a neuron's activity selectively impaired plasticity in basal, but not apical, dendrites. In a related Perspective, Ayelén Groisman and Johannes Letzkus discuss the study and its findings in greater detail.
