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

Hippocampus. 2022 Jul;32(7):488-516. doi: 10.1002/hipo.23422. Epub 2022 May 13.


Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. However, among the disparate forms of neural-circuit heterogeneities, our analyses demonstrated the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. Specifically, despite the expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable across all models through synergistic interactions among these heterogeneities. We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of plasticity profiles. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. Together, our analyses demonstrate that disparate forms of neural-circuit heterogeneities could mechanistically drive plasticity heterogeneity, but also caution against treating neural-circuit heterogeneities as proxies for plasticity heterogeneity. Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.

Keywords: BCM rule; adult neurogenesis; calcium signaling; degeneracy; dentate gyrus; heterogeneity; intrinsic excitability; synaptic plasticity; theta burst stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dentate Gyrus* / physiology
  • Humans
  • Neurogenesis* / physiology
  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Synapses / physiology