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要旨:
As a prominent feature of Rapid Eye Movement (REM) sleep and the
transitional stage from Slow Wave Sleep to REM sleep (the pre-REM
stage), Ponto-Geniculo-Occipital (PGO) waves are hypothesized
to play a critical role in dreaming and memory consolidation [1].
During pre-REM and REM stages, PGO waves appear in two subtypes
differing in number, amplitude and frequency. However, the
mechanisms underlying their generation and propagation across
multiple brain structures, as well as their functions, remains largely unexplored. In particular, contrary to the multiple phasic events
occurring during non-REM sleep (slow waves, spindles and sharpwave
ripples), computational modeling of PGO waves has to the
best of our knowledge not yet been investigated.
Based on experimental evidence in cats, the species were most
extensively studied, we elaborated an existing thalamocortical
model operating in the pre-REM stage [2], and constructed a pontothalamo-
cortical neural mass model consisting of 6 rate-coded neuronal
populations interconnected via biologically-verified synapses
(Fig. 1A). Transient PGO-related activities are elicited by a single or
multiple brief pulses, modelling the input bursts that PGO-triggering
neurons send to cholinergic neurons in the pedunculopontine
tegmentum nucleus (PPT). The effect of acetylcholine (ACh), as the
primarily-affecting neuromodulator during the SWS-to-REM transition,
was also modelled by tuning several critical parameters with
tonically-varying ACh concentration.
Our simulations are able to reproduce deflections in local field
potentials (LFPs), as well as other electrophysiological characteristics
consistent in many respects with classical electrophysiological studies
(Fig. 1B). For example, the duration of both subtypes of thalamic
PGO waves matches that of the PGO recordings with a similar waveform
comprised of a sharp negative peak and a slower positive peak.
The bursting duration of TC and RT neurons (10ms, 25ms) falls in the
range reported by experimental papers (7-15ms, 20-40ms). Consistent
with experimental findings, the simulated PGO waves block
spindle oscillations that occur during pre-REM stage. By incorporating
tonic cholinergic neuromodulation to mimic the SWS-to-REM
transition, we were also able to replicate the electrophysiological
differences between the two PGO subtypes with an ACh-tuned leaky
potassium conductance in TC and RT neurons (Fig. 1C).
These results help clarify the cellular mechanisms underlying thalamic
PGO wave generation, e.g., the nicotinic depolarization of LGin
neurons, whose role used to be under debate, is shown to be critical
for the generation of the negative peak. The model elucidates how
ACh modulates state transitions throughout the wake-sleep cycle,
and how this modulation leads to a recently-reported difference of
transient change in the thalamic multi-unit activities. The simulated
PGO waves also provides us a biologically-plausible framework to
investigate how they take part in the multifaceted brain-wide network
phenomena occurring during sleep and the enduring effects
they may induce through plasticity.
