Abstract
The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.
Highlights
The thalamocortical network plays a central role in cerebral rhythmic oscillations [1,2,3,4] and abnormal thalamocortical rhythms have been associated with disorders such as depression, schizophrenia and Alzheimer’s disease [5,6,7]
In the cat lateral geniculate nucleus (LGN), in vitro and in vivo studies have identified a subset of thalamocortical cells (TCs) that generate high-threshold bursting at theta (θ) and alpha (α) frequency bands and may mediate the cellular mechanism of both θ and α oscillations [12, 17, 18]
Besides θ/α oscillations, the thalamus is critically involved in the genesis of the slow delta rhythm and spindle oscillations that appear at different stages of non-rapid eye movement (NREM) sleep [2, 19, 20]
Summary
The thalamocortical network plays a central role in cerebral rhythmic oscillations [1,2,3,4] and abnormal thalamocortical rhythms have been associated with disorders such as depression, schizophrenia and Alzheimer’s disease [5,6,7]. One important question is whether the thalamus, originally believed to be the “pacemaker” of thalamocortical oscillations [7, 8, 12], is able to independently generate multiple distinct brain rhythms or whether the thalamus requires interaction with the cortex [13,14,15,16]. Answering this question provides the basis for a mechanistic understanding of brain oscillations, and will provide important insights in the design of effective mechanism-based brain stimulation techniques that target abnormal thalamocortical dynamics. It is not known whether the same neural substrate and circuitry for θ and α oscillations could mediate other oscillatory patterns and what controls the transition among these oscillatory states
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