title: Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity.
abstract: The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states.
authors: Department of Mathematics, University of Michigan, 530 Church St, Ann Arbor, MI, 48109, USA.
authors: Scott
authors: S
authors: Knudstrup
authors: Department of Physics and Biophysics Program, University of Michigan, 450 Church St, Ann Arbor, MI, 48109, USA.
authors: Michal
authors: M
authors: Zochowski
authors: Department of Mathematics, University of Michigan, 530 Church St, Ann Arbor, MI, 48109, USA.|Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
authors: Victoria
authors: V
authors: Booth
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000200:Action Potentials; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000109:Acetylcholine
keywords: M current; acetylcholine; computational modelling; network synchrony; phase response curve