Background / Methods

Propofol Alpha and Slow Wave

From Fig 1 of @mukamel_transition_2014{ width=100% }

Why do we care?

Sleep Spindles vs Propofol Alpha

From Fig 1 of @astori_manipulating_2013{ width=100% }

Propofol Mechanisms of Action

  1. Increases $GABA_A$ inhibition:
  2. Decreases thalamocortical (TC) cell H-current conductance ($\downarrow \bar g_H$ )
  3. Decreases Excitation from brainstem ($\downarrow I_{applied}$)

Our Model Thalamus

From Fig 2 of @soplata_thalamocortical_2017{ width=80% }

Overview

Overview

  1. Increase of $GABA_A$ and decrease of TC cell H-current are required for thalamic Alpha oscillations
  2. Thalamic Alpha oscillations are sustained spindles
  3. Interaction between thalamic Alpha and Slow Wave Activity can produce propofol phase-amplitude coupling regimes

$GABA_A$ and H-current changes are required for thalamic Alpha oscillations

Native hyperpolarized thalamus cannot produce Alpha oscillations

From Fig 3 of @soplata_thalamocortical_2017{ width=75% }

Simulating $GABA_A$ increase enables thalamic Alpha oscillations

From Fig 2 of @soplata_thalamocortical_2017{ width=55% }

Alpha requires H-current decrease

From Fig 4 of @soplata_thalamocortical_2017{ width=65% }

Summary So Far

Overview So Far

  1. Increase of $GABA_A$ and decrease of TC cell H-current are required for thalamic Alpha oscillations
  2. Thalamic Alpha oscillations are sustained spindles
  3. Interaction between thalamic Alpha and Slow Wave Activity can produce propofol phase-amplitude coupling regimes

Thalamic Alpha oscillations are sustained spindles

Sustained alpha emerges from Baseline spindles

From Fig 5 of @soplata_thalamocortical_2017{ width=90% }

Summary So Far

Overview So Far

  1. Increase of $GABA_A$ and decrease of TC cell H-current are required for thalamic Alpha oscillations
  2. Thalamic Alpha oscillations are sustained spindles
  3. Interaction between thalamic Alpha and Slow Wave Activity can produce propofol phase-amplitude coupling regimes

Alpha-SWO Coupling

Slow Wave Oscillations

From Fig 1 of @crunelli_slow_2010{ width=100% }

Phase-amplitude Coupling Switches

From Fig 1 of @mukamel_transition_2014{ width=70% }

Our Full Model Network

From Fig 9 of @soplata_thalamocortical_2017{ width=60% }

Simulating UP vs DOWN states

From Fig 7 of @soplata_thalamocortical_2017{ width=70% }

Simulating UP vs DOWN states

From Fig 7 of @soplata_thalamocortical_2017{ width=70% }

Trough-max thalamic alpha

From Fig 7 of @soplata_thalamocortical_2017{ width=70% }

Trough-max comparison

From Fig1 and 7 of @soplata_thalamocortical_2017{ width=70% }

Peak-max thalamic alpha

From Fig1 and 7 of @soplata_thalamocortical_2017{ width=70% }

Peak-max comparison

From Fig1 and 7 of @soplata_thalamocortical_2017{ width=70% }

Coupling Summary So Far

Conclusions

Conclusions 1

  1. Propofol sustained alpha may come from its $GABA_A$ increase and H-current decrease in the thalamus.
  2. This propofol alpha is dependent on the spindling dynamics of the thalamus.

Conclusions 2

  1. During “trough-max” propofol coupling, the thalamus may cause the sustained Alpha in the DOWN/trough phase. Similarly, in “peak-max” coupling, the thalamus may cause the sustained Alpha seen during the UP/peak phase.
  2. Increased hyperpolarization of the thalamus is sufficient to switch from trough-max thalamic firing to peak-max thalamic firing, and vice versa.

Implications

Acknowledgements

Simulation Code

Our lab uses and develops the DynaSim Simulator originally created by Jason Sherfey. All the code necessary to run these simulations is available on GitHub here! { width=100% }

Appendix

Detail: $T_{window}$ is critical

{ width=85% }

Detail: Propofol Alpha mechanism

{ width=75% }

References

CSS

##