Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation

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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. Computational modeling has served as an important tool to understand the cellular and circuit mechanisms of thalamocortical oscillations. However, most of the existing thalamic models focus on only one particular oscillatory pattern such as alpha or spindle oscillations. Thus, it remains unclear whether the same thalamic circuitry on its own could generate all major oscillatory patterns and if so what mechanisms underlie the transition among these distinct states. Here we present a unified model of the thalamus that is capable of independently generating multiple distinct oscillations corresponding to different physiological conditions. We then mapped out the different thalamic oscillations by varying the ACh/NE modulatory level and input level systematically. Our simulation results offer a mechanistic understanding of thalamic oscillations and support the long standing notion of a thalamic “pacemaker”. It also suggests that pathological oscillations associated with neurological and psychiatric disorders may stem from malfunction of the thalamic circuitry.
Funding Information
  • National Institute of Mental Health (MH101547)
  • National Institute of Mental Health (MH105557)
  • National Institute on Deafness and Other Communication Disorders (DC013872)

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