In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca²⁺) concentration, thus reducing the Ca²⁺-dependent potassium (K⁺) current. In this way, the GABA-mediated hyperpolarization replaces Ca²⁺-dependent K⁺ current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally.

The dynamics of neuronal excitability determine the neuron’s response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency “balanced” state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization by mutual excitation. Dopamine neurons play a central role in guiding motivated behaviors. However, complete understanding of computations these neurons perform to encode rewarding and salient stimuli is still forthcoming. Network connectivity influences neural responses to stimuli, but so do intrinsic excitability properties of individual neurons, as such properties define synchronization qualities and neural coding strategy. We investigated the excitability type of the DA neuron and found that, depending on the synaptic and intrinsic current composition, DA neurons can switch from type I to type II excitability. In short, without synaptic inputs or under balanced excitatory and inhibitory inputs DA neurons exhibits type I excitability, while excitatory AMPAR inputs can switch the neuron to type II. Type I neurons are best suited for coding the stimulus intensity due to their ability to decrease the firing rate smoothly. Type I excitability might be important for achieving low a basal DA concentration necessary for normal brain functioning. Switching to type II excitability further enables robust transient DA release of heterogeneous DA neuron population in response to correlated inputs, partially due to evoked population synchrony.

Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40\% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.

Formation of synchronous activity patterns is an essential property of neuronal networks that has been of central interest to synchronization theory. Chimera states, where both synchronous and asynchronous activities of neurons co-exist in a single network, are particularly poignant examples of such patterns, whose dynamics and multistability may underlie brain function, such as cognitive tasks. However, dynamical mechanisms of coherent state formation in spiking neuronal networks as well as ways to control these states remain unclear. In this paper, we take a step in this direction by considering the evolution of chimera states in a network of class II excitable Morris–Lecar neurons with asymmetrical nonlocal inhibitory connections. Using the adaptive coherence measure, we are able to partition the network parameter space into regions of various collective behaviors (antiphase synchronous clusters, traveling waves, different types of chimera states as well as a spiking death regime) and have shown multistability between the various regimes. We track the evolution of the chimera states as a function of changed key network parameters and found transitions between various types of chimera states. We further find that the network can demonstrate long transients leading to quasi-persistence of activity patterns in the border regions hinting at near-criticality behaviors.

This paper introduces a novel approach for classifying multidimensional physiological and clinical data using Synolitic Graph Neural Networks (SGNNs). SGNNs are particularly good for addressing the challenges posed by high-dimensional datasets, particularly in healthcare, where traditional machine learning and Artificial Intelligence methods often struggle to find global optima due to the “curse of dimensionality”. To apply Geometric Deep Learning we propose a synolitic or ensemble graph representation of the data, a universal method that transforms any multidimensional dataset into a network, utilising only class labels from training data. The paper demonstrates the effectiveness of this approach through two classification tasks: synthetic and fMRI data from cognitive tasks. Convolutional Graph Neural Network architecture is then applied, and the results are compared with established machine learning algorithms. The findings highlight the robustness and interpretability of SGNNs in solving complex, high-dimensional classification problems.