Although such plasticity heterogeneity has typically been overlooked in analyzing the impact of plasticity protocols, a growing body of experimental evidence identifies crucial roles for plasticity heterogeneity in neural encoding and storage. There are several lines of evidence from in vitro and in vivo electrophysiological experiments for such plasticity heterogeneity, spanning different neuronal and synaptic subtypes (Beck et al., 2000 Bliss & Lomo, 1973 Davis et al., 2004 Greenstein et al., 1988 Kobayashi et al., 2013 Koranda et al., 2008 Larson & Munkacsy, 2015 Li et al., 2017 McHugh et al., 2007 Pavlides et al., 1988 Rathour & Narayanan, 2019 Shors & Dryver, 1994 Sjostrom et al., 2008 Wang et al., 1997). Instead, they exhibit plasticity heterogeneity across synapses and neurons, manifesting as pronounced variability in the observed changes. Neurons and synapses of the same subtype receiving identical plasticity-inducing activity patterns do not manifest identical levels of plasticity.
Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.
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. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths.
We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of 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. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. 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 each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored.
Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns.