Sleep spindles in primates: Modeling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits

卷:7

Article

关键词: CORTICOTHALAMIC PROJECTIONS;    NUCLEUS-RETICULARIS;    PREFRONTAL CORTEX;    CORTICOCORTICAL COMMUNICATION;    ATTENTIONAL MODULATION;    ANATOMICAL EVIDENCE;    GABAERGIC NEURONS;    REGULAR SPIKING;    AUDITORY-CORTEX;    SINGLE-FIBER;   

DOI  :  10.1162/netn_a_00311

来源: SCIE

【 摘 要 】

Author Summary Sleep spindles are slow brain oscillations that are associated with the beginning of deep sleep, learning, and memory storage and are disrupted in brain disorders. We developed a computational model that can simulate sleep spindles in humans, using novel data on the organization and connectivity of circuits that link the thalamus and cortex, and generate spindles. Our model sheds light on the role of excitatory and inhibitory neurons in the network dynamics and the functional consequences of differential engagement and connectivity of thalamic and cortical areas involved in typical brain function. Our work also establishes a framework for the future study of the dynamics of variable types of sleep spindles and their disruption that can lead to deficits in sleep, memory, and attention. Sleep spindles are associated with the beginning of deep sleep and memory consolidation and are disrupted in schizophrenia and autism. In primates, distinct core and matrix thalamocortical (TC) circuits regulate sleep spindle activity through communications that are filtered by the inhibitory thalamic reticular nucleus (TRN); however, little is known about typical TC network interactions and the mechanisms that are disrupted in brain disorders. We developed a primate-specific, circuit-based TC computational model with distinct core and matrix loops that can simulate sleep spindles. We implemented novel multilevel cortical and thalamic mixing, and included local thalamic inhibitory interneurons, and direct layer 5 projections of variable density to TRN and thalamus to investigate the functional consequences of different ratios of core and matrix node connectivity contribution to spindle dynamics. Our simulations showed that spindle power in primates can be modulated based on the level of cortical feedback, thalamic inhibition, and engagement of model core versus matrix, with the latter having a greater role in spindle dynamics. The study of the distinct spatial and temporal dynamics of core-, matrix-, and mix-generated sleep spindles establishes a framework to study disruption of TC circuit balance underlying deficits in sleep and attentional gating seen in autism and schizophrenia.