SyNC, a Computationally Extensive and Realistic Neural Net to Identify Relative Impacts of Synaptopathy Mechanisms on Glutamatergic Neurons and Their Networks in Autism and Complex Neurological Disorders

Synaptic function and experience-dependent plasticity across multiple synapses are dependent on the types of neurons interacting as well as the intricate mechanisms that operate at the molecular level of the synapse. To understand the complexity of information processing at synaptic networks will rely in part on effective computational models. Such models should also evaluate disruptions to synaptic function by multiple mechanisms. By co-development of algorithms alongside hardware, real time analysis metrics can be co-prioritized along with biological complexity. The hippocampus is implicated in autism spectrum disorders (ASD) and within this region glutamatergic neurons constitute 90% of the neurons integral to the functioning of neuronal networks. Here we generate a computational model referred to as ASD interrogator (ASDint) and corresponding hardware to enable in silicon analysis of multiple ASD mechanisms affecting glutamatergic neuron synapses. The hardware architecture Synaptic Neuronal Circuit, SyNC, is a novel GPU accelerator or neural net, that extends discovery by acting as a biologically relevant realistic neuron synapse in real time. Co-developed ASDint and SyNC expand spiking neural network models of plasticity to comparative analysis of retrograde messengers. The SyNC model is realized in an ASIC architecture, which enables the ability to compute increasingly complex scenarios without sacrificing area efficiency of the model. Here we apply the ASDint model to analyse neuronal circuitry dysfunctions associated with autism spectral disorder (ASD) synaptopathies and their effects on the synaptic learning parameter and demonstrate SyNC on an ideal ASDint scenario. Our work highlights the value of secondary pathways in regard to evaluating complex ASD synaptopathy mechanisms. By comparing the degree of variation in the synaptic learning parameter to the response obtained from simulations of the ideal scenario we determine the potency and time of the effect of a particular evaluated mechanism. Hence simulations of such scenarios in even a small neuronal network now allows us to identify relative impacts of changed parameters and their effect on synaptic function. Based on this, we can estimate the minimum fraction of a neuron exhibiting a particular dysfunction scenario required to lead to complete failure of a neural network to coordinate pre-synaptic and post-synaptic outputs.

Automated summary

The complexity of synaptic function and plasticity relies on the types of neurons and molecular mechanisms at the synaptic level. Computational models like ASDint and hardware like SyNC enable analysis of ASD mechanisms affecting glutamatergic neuron synapses, expanding neural network models of plasticity. They allow for evaluation of the impact of changed parameters on synaptic function and potential failure of neural networks.