Implementing the cellular mechanisms of synaptic transmission in a neural mass model of the thalamocortical circuitry

A novel direction to existing neural mass modeling technique is proposed where the commonly used “alpha function” for representing synaptic transmission is replaced by a kinetic framework of neurotransmitter and receptor dynamics. The aim is to underpin neuro-transmission dynamics associated with abnormal brain rhythms commonly observed in neurological and psychiatric disorders. An existing thalamocortical neural mass model is modified by using the kinetic Q1 framework for modeling synaptic transmission mediated by glutamatergic and GABA (gamma-aminobutyric-acid)-ergic receptors. The model output is compared qualitatively with existing literature on in vitro experimental studies of ferret thalamic slices, as well as on single-neuron-level model based studies of neuro-receptor and transmitter dynamics in the thalamocortical tissue. The results are consistent with these studies: the activation of ligand-gated GABA receptors is essential for generation of spindle waves in the model, while blocking this pathway leads to low-frequency synchronized oscillations such as observed in slow-wave sleep; the frequency of spindle oscillations increase with increased levels of post-synaptic membrane conductance for AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid) receptors, and blocking this pathway effects a quiescent model output. In terms of computational efficiency, the simulation time is improved by a factor of 10 compared to a similar neural mass model based on alpha functions. This implies a dramatic improvement in computational resources for large-scale network simulation using this model. Thus, the model provides a platform for correlating high-level brain oscillatory activity with low-level synaptic attributes, and makes a significant contribution toward advancements in current neural mass modeling paradigm as a potential computational tool to better the understanding of brain oscillations in sickness and in health

Kinetic modelling of synaptic functions in the alpha rhythm neural mass model

In this work, we introduce the kinetic framework for modelling synaptic transmission in an existing neural mass model of the thalamocortical circuitry to study Electroencephalogram (EEG) slowing within the alpha frequency band (8–13 Hz), a hallmark of Alzheimer’s disease (AD). Ligand-gated excitatory and inhibitory synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and GABAA (gamma-amino-butyric acid) receptors respectively are modelled. Our results show that the concentration of the GABA neurotransmitter acts as a bifurcation parameter, causing the model to switch from a limit cycle mode to a steady state. Further, the retino-geniculate pathway connectivity plays a significant role in modulating the power within the alpha band, thus conforming to research proposing ocular biomarkers in AD. Overall, kinetic modelling of synaptic transmission in neural mass models has enabled a more detailed investigation into the neural correlates underlying abnormal EEG in AD