Glutamate spillover drives robust all-or-none dendritic plateau potentials—an in silico investigation using models of striatal projection neurons

Abstract

Plateau potentials are a critical feature of neuronal excitability, but their all-or-none behavior is not easily captured in modeling. In this study, we investigated models of plateau potentials in multi-compartment neuron models and found that including glutamate spillover provides robust all-or-none behavior. This result arises due to the prolonged duration of extrasynaptic glutamate. When glutamate spillover is not included, the all-or-none behavior is very sensitive to the steepness of the Mg2+ block. These results suggest a potentially significant role of glutamate spillover in plateau potential generation, providing a mechanism for robust all-or-none behavior across a wide range of slopes of the Mg2+ block curve. We also illustrate the importance of the all-or-none plateau potential behavior for nonlinear computation with regard to the nonlinear feature binding problem.

Local, calcium- and reward-based synaptic learning rule that enhances dendritic nonlinearities can solve the nonlinear feature binding problem

“…The random setup was tested with two glutamate spillover models: The first model assumed that thresholded glutamate spillover is branch-specific, building on the notion that the single branch act as a single computational unit (Losonczy and Magee, 2006;. The second assumed that spillover is accumulative (Trpevski et al, 2023). Both spillover versions increase the performance of our neuron model, further certifying the necessity of supralinear responses for solving the NFBP.…”

“…Here we will focus on the setup of the learning rule and only give a short summary of the neuron and synapse models, focusing on changes compared to previously published versions. For a detailed description of the neuron model setup, see Lindroos et al, (2018), Lindroos &Hellgren Kotaleski, (2021), andTrpevski et al, (2023).…”

“…The nonlinear, sigmoidal voltage sensitivity of the NMDA receptors is a crucial element for formation of dendritic plateau potentials. We use a model for generating plateau potentials first presented in Gao et al, (2021) and adjusted to SPNs (Trpevski et al, 2023). To produce robust, all-or-none plateau potentials, glutamate spillover from the synaptic cleft that activates extrasynaptic NMDA receptors is included in the model.…”

“…A plateau potential is generated when a critical level of total NMDA conductance in a dendritic segment is reached (accomplished here by the addition of more synapses in a cluster and by glutamate spillover). Reaching the spillover threshold produces a sudden and robust increase in NMDA conductance, caused by the activation of extrasynaptic NMDA receptors (where the clearance of glutamate is assumed to be slower), thus triggering an all-or-none plateau potential as investigated in Trpevski et al, (2023).…”

“…This hypothetical construct assumes that concurrent activation of a critical mass of co-activated synapses in a single dendritic branch would trigger both plateau potentials and a significant rise in calcium levels despite that the synapses are not spatially pre-clustered, endowing the dendrites with supralinear responses even without closely clustered synapses. We also tested a more gradual spillover model proposing that each synapse could contribute incrementally to a cumulative spillover effect, instead of using a sharp glutamate threshold (see Trpevski et al, 2023). This modification provided a reduced level of nonlinearity compared to the branch-specific spillover model but still led to an increase in learning effectiveness.…”