Neuroscience Research
Division, Instituto Nacional de Psiquiatria,
Mexico
Introduction : One of the effects
detected in the early experimental models of
electrical vagal stimulation was sleep
induction. Grastyan et al. were the first to
describe the occasional appearance of sleep
spindles during vagus nerve stimulation (VNS).
Padel and Dell (1965), using encéphale
isolé preparations obtained what they
called "aortic vagus" response, characterized by
immediate myosis, followed by cortical
synchronization, maintained after VNS.
Further on, Puizillout and Foutz (1977) found
that VNS produces complete cycles of all sleep
stages, and increases slow wave sleep preceded
by rapid eye movement (REM) sleep. In addition,
it promotes the sudden transition from waking
stage to REM sleep in sleep-deprived cats. More
over, an enhanced frequency of REM sleep
episodes was found, suggesting that VNS may be a
triggering factor of this sleep stage.
However, depending on the vagal stimulation
parameter used in experimental animal models,
either electrographical synchronization or
desynchronization, can be produced. In pioncer
works in cats, VNS at frequencies of 24 to 50 Hz
produced rapid activity of the orbito-frontal
cortex (Breme and Bonnet, 1951). In subsequent
works using encéphale isolé
preparations in cats, VNS (50 Hz from 0.1 to 2 v
intensity) produced cortical desynchronization
and inhibition of sleep spindles (Zanchetti et
al., 1952). On the othe hand, Penaloza-Rojas
(1964) stimulating the vagus nerve with direct
current found electrographic
synchronization.
Chase and Nakamura (1968) and Chase et al.
(1966 1967) reported that VNS-induced
electrographic changes are associated with the
activation of different types of nerve fibers;
frequencies of 70 Hz and over 3 v produce
electroencephalogram (EEG) desynchronization.
Using the same frequency but with lower
intensities, synchronization is induced,
suggesting that this effect results from
stimulation of only myelinated fibers.
Stimulation intensities and frequencies that
induce desynchronization are those capable of
stimulating the fibers that conduct from 1 to 15
m/s (Chase and Nakamura, 1968).
The nucleus of the solitary tract (NTS)
receiving the majority of vagus nerve afferences
has been involved in sleep-wakefulness cycle
mechanisms. Vigier and Portalier (1979)
described projections of the area postrema to
the NTS and the locus coeruleus. Besides,
afferents and efferents have been described from
these nuclei to the dorsal motor nucleus of the
vagus nerve (Vigier and Rouvière,
1979).
Recently, the effect of VNS on the
experimental model of epilepsy named "kindling"
in the cat was reported, and some changes in the
sleep-wakefulness cycle produced by VNS were
described (Femàndez-Guardiola et al.,
1998, 1999). Nevertheless, there are no studies
in which the VNS effect on the sleep-wakefulness
cycle of freely moving cats bas been analyzed.
Thus, the purpose of the present study is to
report the changes on the different sleep
stages, as well as on the behavior induced by
chronic VNS. [...]
Discussion : Our results complement
the previous findings about VNS sleep studies,
in which the animals were under anesthesia or
encéphale isolé preparation. Thus,
we recorded the EEG during 23 h in freely moving
cats, and observed sleep changes outside VNS
periods as well as the behavior while VNS was
performed.
Behavioral effects Abdominal
contractions and compulsive eating could be
induced by efferent parasympathetic projections
of the vagus nerve towards the esophagus,
stomach, and gut . Swallowing and licking are
behaviors produced by the activation of the
ambiguous nucleus, which controls the phonation
and swallowing muscles. The vomit reflex is a
result of theactivation of the area postrema
through the NTS. Ipsilateral myosis, blinking,
ocular movements in bursts, and upward gaze are
induced by the activation of the oculomotor
nucleus and the Edinger-Westphal nucleus,
through central afferent projections of the NTS
).
Effect on sleep The effect of VNS on
REM sleep could be due to the central afferent
projections of the vagus nerve. These originate
in the nodose ganglion and most fibers are
directed towards the NTS. The role of the NTS in
sleep seems to be diverse. In cats, different
groups of neurons have been observed to display
changes in their triggering pattem depending on
the animal's sleep stage.
The importance of endogenous opioids of the
NTS on slow wave sleep has been marked. In
addition, the NTS has cholinergic and excitatory
amino acid projections toward structures
involved in different mechanisms of REM sleep
such as the PBL, the TAM, the locus coeruleus
alpha and subcoeruleus. In addition, it has been
proposed that the NTS could play a role in REM
sleep by way of its serotoninergic projections
towards the PBL. Also, the NTS presents an
increase in C-fos in animals with REM sleep
increased by auditory stimulation.
The importance of PBL and locus coeruleus
during the tonic and phasic events of REM sleep
has been well documented. A lasting induction of
REM sleep has been attained by direct
cholinergic stimulation of both PBL and TAM ,
with persistent increase of PGO potentials in
both cases. The rise in density of these
potentials in the present experiments could be
due to the cholinergic activation favored by VNS
in these areas through the NTS.
On the other hand, it should be noted that
sudden transitions from wakefulness to REM sleep
(narcoleptic reflex) were described before in
cats with VNS in encéphale isolé
preparations and in sleep-deprived cats. In our
present work, freely moving cats with no
anesthesia and VNS present a narcoleptic reflex
despite exhibiting increased REM sleep.
Some afferent fibers to the NTS with high
density of orexin immunoreactivity may be of
importance for the narcoleptic reflex, as
orexins (hypocretins) play a key role in
narcolepsy.
Conclusion : We conclude that VNS
influences REM sleep through vagal afferences
related with areas that play a role in this
sleep stage. The relevance of 23-h recordings
must be emphasized, since long-term changes were
observed that were reflected on PGO wave
increase, total REM sleep time, and sudden
transitions from waking stage to REM
sleep.
