Role
of the Lateral Preoptic Area in Sleep-Related
Erectile Mechanisms and Sleep Generation in the
Rat
Markus H. Schmidt, Jean-Louis
Valatx, Kazuya Sakai, Patrice Fort, and Michel
Jouvet
Cleveland Clinic
Foundation, Department of Neurology, Cleveland,
Ohio 44195, and University of Claude Bernard,
Institut National de la Santé et de la
Recherche Médicale U480, Lyon,
France
Resume : Penile erections are a
characteristic phenomenon of paradoxical sleep
(PS), or rapid eye movement sleep. Although the
neural mechanisms of PS-related erections are
unknown, the forebrain likely plays a critical
role (Schmidt et al., 1999). The preoptic area
is implicated in both sleep generation and
copulatory mechanisms, suggesting it may be a
primary candidate in PS erectile control.
Continuous recordings of penile erections, body
temperature, and sleepÐwake states were
performed before and up to 3 weeks after
ibotenic acid lesions of the preoptic forebrain
in three groups of rats. Neurotoxic lesions
involving the medial preoptic area (MPOA) and
anterior hypothalamus (n 5 5) had no significant
effects on either erectile activity or
sleepÐwake architecture. In contrast,
bilateral lesions of the lateral preoptic
region, with (n 5 4) or without (n 5 5) MPOA
involvement, resulted in a significant decrease
in the number of erections per hour of PS,
number of PS-related erections, and PS phases
exhibiting an erection. Lesion analysis revealed
that the candidate structuresfor PS erectile
control include both the lateral preoptic area
(LPOA) and ventral division of the bed nucleus
of the stria terminalis; however, lesions of the
LPOA were the most effective in disrupting PS
erectile activity. LPOA lesioning also resulted
in a long-lasting insomnia, characterized by the
significant increase in wakefulness and decrease
in slow wave sleep (SWS). PS architecture and
waking-state erections remained unchanged after
lesion in all groups. These data identify an
essential role of the LPOA in both PS-related
erectile mechanisms and SWS generation.
Moreover, higher erectile mechanisms appear to
be context-specific because LPOA lesioning
selectively disrupted PS-related erections while
leaving waking-state erections intact.
Intro : Paradoxical sleep (PS), also
known as rapid eye movement sleep, is
characterized by several tonic and phasic
phenomena, including cortical desynchronization,
rapid eye movements, general muscle atonia, and
penile erections. Whereas the neural control of
PS related erections remains unknown, the
executive mechanisms generating PS and its other
tonic and phasic events are relatively well
elucidated and localized within the mesopontine
tegmentum and rostral medulla (Sakai 1985; Jones
1991). Using a new technique of chronic penile
erection recording in the rat (Schmidt et
al.,1995), we recently demonstrated that
mesencephalic transections disrupt PS erectile
activity even though PS remains otherwise
qualitatively intact (Schmidt et al., 1999).
These data suggest that forebrain structures
rostral to the transection are necessary for the
production of PS-related erections. The source
of this forebrain control currently is a matter
of speculation. Numerous forebrain structures
have been implicated in reproductive mechanisms
and, therefore, are potential candidates in
sleep-related erectile control. Lesion,
stimulation, and unit recording studies have
elucidated an erectile role of the
paraventricular nucleus (Melis et al., 1994),
medial preoptic area (MPOA) (Giuliano et al.,
1996), bed nucleus of the stria terminalis
(BNST) (Valcourt and Sachs 1979), hippocampus
(Chen et al., 1992), amygdala (Kondo 1992), and
olfactory bulbs (Fernandez-Fewell and Meredith,
1995). Recent data suggest that some of these
structures may be responsible for
context-specific erectile control (Sachs, 1995).
We hypothesize that the preoptic area may be a
primary forebrain candidate in sleep-related
erectile control given its role in both
reproductive physiology and slow wave sleep
(SWS) generation. The MPOA, for example, has
long been implicated in copulatory mechanisms
because its lesioning eliminates copulatory
behavior in every species examined (Sachs and
Meisel, 1988). Moreover, low androgen states
disrupt PS-related erections in humans (Carani
et al., 1992), and the MPOA contains
androgensensitive neurons important for
reproductive physiology (Cherry et al., 1992).
With regard to sleep and wakefulness, both the
MPOA and lateral preoptic area (LPOA) are
described as "sleep centers" because their
lesioning results in a long-lasting insomnia
(Lucas and Sterman, 1975; Szymusiak, and McGinty
1986; Sallanon et al., 1989). Stimulation,
neuroanatomical, and single-unit recording
studies suggest an important role of the
preoptic area in the generation of SWS and
inhibition of waking mechanisms (Siegel and
Wang, 1974; Ogawa and Kawamura, 1988; Sherin et
al., 1998). Although the importance of the MPOA
in copulatory behavior is well established, the
relative contribution of theMPOA and LPOA in
sleep generation remains controversial. In the
following experiments, cytotoxic lesions of the
preoptic basal forebrain were performed using
ibotenic acid in an attempt to localize
forebrain structures involved in PS-related
erections. Moreover, neurotoxic lesions
primarily were limited to either the MPOA, LPOA,
or both in three groups of rats to differentiate
the relative contributions of these two
structures in sleep-related erectile control and
sleep generation. Continuous polygraphic
recordings of penile erections, sleepÐwake
states, and body temperature were performed
before and up to 3 weeks after neurotoxic
lesions.
Frank, M. G.et
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