A subset of mouse hippocampus CA1 pyramidal neurons learns sparse synaptic input patterns.

Synaptic plasticity in the hippocampus is fundamental to learning and memory, yet few studies examine how pattern learning occurs across multiple synapses. Such cross-synapse learning is fundamental to emergent properties of pattern discrimination and generalisation, which depend on assumptions about independence of plasticity and linearity of summation. We used sparse optogenetic spatio-temporal pattern stimulation in the CA3 coupled with postsynaptic depolarization to elicit plasticity on CA1 pyramidal neurons, and found that trained patterns were selectively strengthened, but only in a subset of postsynaptic cells. Increased resting membrane potential and background mini-EPSP rates were predictive of learner cells. Summation following plasticity became more linear in learners compared to non-learners, consistent with the observed elevated post-stimulus hyperpolarization on non-learner cells. Thus our exploration of biologically plausible sparse activity supports pattern-selective learning, but in a heterogeneous manner modulated by both cell-intrinsic and network features.