Interacting Mechanisms Driving Synchrony in Neural Networks with Inhibitory Interneurons

[摘要] Computational neuroscience contributes to our understanding of the brain by applying techniques from fields including mathematics, physics, and computer science to neuroscientific problems that are not amenable to purely biologic study. One area in which this interdisciplinary research is particularly valuable is the proposal and analysis of mechanisms underlying neural network behaviors. Neural synchrony, especially when driven by inhibitory interneurons, is a behavior of particular importance considering this behavior play a role in neural oscillations underlying important brain functions such as memory formation and attention. Typically, these oscillations arise from synchronous firing of a neural population, and thus the study of neural oscillations and neural synchrony are deeply intertwined. Such network behaviors are particularly amenable to computational analysis given the variety of mathematical techniques that are of use in this field. Inhibitory interneurons are thought to drive synchrony in ways described by two computational mechanisms: Interneuron Network Gamma (ING), which describes how an inhibitory network synchronizes itself; and Pyramidal Interneuron Network Gamma (PING), which describes how a population of interneurons inter-connected with a population of excitatory pyramidal cells (an E-I network) synchronizes both populations. As first articulated using simplified interneuron models, these mechanisms find network properties are the primary impetus for synchrony. However, as neurobiologists uncover interneurons exhibiting a vast array of cellular and intra-connectivity properties, our understanding of how interneurons drive oscillations must account for this diversity. This necessitates an investigation of how changing interneuron properties might disrupt the predictions of ING and PING, and whether other mechanisms might interact with or disrupt these network-driven mechanisms.In my dissertation, I broach this topic utilizing the Type I and Type II neuron classifications, which refer to properties derived from the mathematics of coupled oscillators. Classic ING and PING literature typically utilize Type I neurons which always respond to an excitatory perturbation with an advance of the subsequent action potential. However, many interneurons exhibit Type II properties, which respond to some excitatory perturbations with a delay in the subsequent action potential. Interneuronal diversity is also reflected in the strength and density of the synaptic connections between these neurons, which is also explored in this work. My research reveals a variety of ways in which interneuronal diversity alters synchronous oscillations in networks containing inhibitory interneurons and the mechanisms likely driving these dynamics. For example, oscillations in networks of Type II interneurons violate ING predictions and can be explained mechanistically primarily utilizing cellular properties. Additionally, varying the type of both excitatory and inhibitory cells in E-I networks reveals that synchronous excitatory activity arises with different network connectivities for different neuron types, sometimes driven by cellular properties rather than PING. Furthermore, E-I networks respond differently to varied strengths of inhibitory intra-connectivity depending upon interneuron type, sometimes in ways not fully accounted for by PING theory. Taken together, this research reveals that network-driven and cellularly-driven mechanisms promoting oscillatory activity in networks containing inhibitory interneurons interact, and oftentimes compete, in order to dictate the overall network dynamics. These dynamics are more complex than those predicted by the classic ING and PING mechanisms alone. The diverse dynamical properties imparted to oscillating neural networks by changing inhibitory interneuron properties provides some insight into the biological need for such variability.

[发布机构] University of Michigan

[效力级别] Neural Oscillations

[关键词] Computational Neuroscience;Neural Oscillations;Neural Networks;Inhibitory Interneurons;Phase Response Curves;Synchrony;Mathematics;Science;Applied and Interdisciplinary Mathematics