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bioRxiv · 10.1101/2025.11.17.688856

Opposite and complementary roles of the two calcium thresholds for inducing LTP and LTD in models of striatal projection neurons

Trpevski, D.
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Abstract

Synaptic plasticity has been shown to occur when calcium, flowing into the synapse due to incoming stimuli, surpasses a threshold level. This threshold level is modifiable through a process called metaplasticity. Some neurons, such as the striatal projection neurons, use different sources of calcium as the signal for synaptic strengthening (long-term potentiation, LTP) or weakening (long-term depression, LTD), resulting in them having two thresholds for inducing plasticity. In this study, we show that metaplasticity enables synapses undergoing both LTP and LTD during learning to selectively express just one form of plasticity (either LTP or LTD). To show this, we use the linear and nonlinear feature binding problem (FBP and NFBP) because their input patterns share features, exposing synapses to such competing LTP and LTD processes. In particular, we identify opposite and complementary roles of metaplasticity in the two thresholds for inducing LTP and LTD: metaplasticity in one threshold (e.g. LTD) allows synaptic plasticity of the opposite type (e.g. LTP) to be properly expressed. This happens because metaplasticity in the LTD threshold protects strengthened synapses from weakening, thus allowing them to persistently increase during learning (and encode learned patterns). Similarly, metaplasticity in the LTP threhsold prevents weakened synapses from strengthening, thus allowing them to persistently decrease. Under more general conditions for triggering metaplasticity, reversal learning can also be solved, demonstrating metaplasticitys importance for solving the plasticity-stability dilemma. Finally, we show that even though a single calcium threshold is sufficient for solving the FBP, NFBP and reversal learning, two calcium thresholds allow separate control over LTP and LTD.

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Trpevski, D.. 2025-11-18. Opposite and complementary roles of the two calcium thresholds for inducing LTP and LTD in models of striatal projection neurons. https://doi.org/10.1101/2025.11.17.688856

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