Neuromodulation of short-term synaptic dynamics examined in a mechanistic model based on kinetics of calcium currents

Network plasticity arises in large part due to the effects of exogenous neuromodulators. We investigate the neuromodulatory effects on short-term synaptic dynamics. The synapse from the lateral pyloric (LP) to the pyloric dilator (PD) neuron in the pyloric network of the crab C. borealis has both spike-mediated and non-spike-mediated (graded) components. Previous studies have shown that the graded component of this synapse exhibits short-term depression. Recent results from our lab indicate that in the presence of the neuromodulatory peptide proctolin, low-amplitude presynaptic stimuli switch the short-term dynamics of this graded component from depression to facilitation. In this study, we show that this facilitation is correlated with the activation of a presynaptic inward current that is blocked by Mn²⁺, suggesting that it is a slowly accumulating Ca²⁺ current. We modify a mechanistic model of synaptic release by assuming that the low-voltage-activating Ca²⁺ current in our system is composed of two currents with fast (I_CaF) and slow (I_CaS) kinetics. We show that if proctolin adjusts the activation rate of I_CaS, this leads to accumulation of local intracellular Ca²⁺ in response to multiple presynaptic voltage stimuli, which, in turn, results in synaptic facilitation. Additionally, we assume that proctolin increases the maximal conductances of Ca²⁺ currents in the model, consistent with the increased synaptic release found in the experiments. We find that these two presynaptic actions of proctolin in the model are sufficient to describe its actions on the short-term dynamics of the LP to PD synapse.