Wright, W. J., Hedrick, N. G., & Komiyama, T. (2025). Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning. Science, 388(6744), 322-328. https://www.science.org/doi/full/10.1126/science.ads4706
Coexpression of glutamate sensor (iGluSnFR3) and calcium indicator (RCaMP2) to monitor individual synaptic inputs and neuronal response along with structural changes (sLTP / sLTD) of dendritic spine synapses
Mouse motor cortex Layer 2/3

Wright et al. performed two photon imaging in mouse motor cortex while the mouse was learning a motor task (lever press to tone). The authors coexpressed the glutamate sensor (iGluSnFR3) and calcium indicator (RCaMP2) in a subset of layer 2/3 pyramidal neurons. This allowed them to simultaneously monitor the synaptic inputs onto a neuron and the neuron’s response to those inputs over several sessions during learning, and to simultaneously monitor changes in the size of the dendritic spine synapses that constituted the motor learning. In this way the authors could ask the question “What functional correlations give rise to synaptic potentiation?” The authors found that potentiation of an apical spine is predicted by that spine’s chance of being coactive with nearby spines (within 20 microns) and was independent of activity of the postsynaptic neuron itself. In fact, blocking postsynaptic action potentials did not affect this apical spine plasticity. In contrast, potentiation of dendritic spines on the basal dendrites was predicted by coincident of presynaptic inputs with postsynaptic action potentials -suggesting basal dendrites employ something like a Hebbian learning rule.
“Using in vivo longitudinal imaging with single-synapse resolution in the mouse motor cortex during motor learning, we found that apical and basal dendrites of layer 2/3 (L2/3) pyramidal neurons showed distinct activity-dependent synaptic plasticity rules. The strengthening of apical and of basal synapses is predicted by local coactivity with nearby synapses and activity coincident with postsynaptic action potentials, respectively.”