Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Abstract

Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic, unbiased, and physiologically constrained search to identify the mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneous plasticity profiles obtained with two different induction protocols. However, prior predictions about strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult-neurogenesis-induced structural heterogeneities were accounted for. Strikingly, despite the concomitant expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable through synergistic interactions among these heterogeneities. Importantly, consequent to strong relationships with intrinsic excitability measurements, we found that synaptic plasticity in the physiological range was achieved in immature cells despite their electrophysiologically-observed weak synaptic strengths. Together, our analyses unveil the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. Broadly, these analyses emphasize that the mechanistic origins of and the implications for plasticity heterogeneities need quantitative characterization across brain regions, particularly focusing on context-specific encoding of learned behavior.