STH MULTIDISCIPLINARY INTERNATIONAL

Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD

CONFERENCE ABSTRACTS 2. SLEEP AND BEHAVIOR

CONTRIBUTION OF GABA TO INTEGRATIVE ACTIVITY OF THE NERVOUS «CENTRES» PARTICIPATING IN THE CONTROL OF SLEEP-WAKE BEHAVIOR

I.V. Ekimova, Iu.F. Pastukhov Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia

A balance between inhibitory and excitatory systems of neurotransmission in the CNS is the basis of the regulation of sleep-wake behavior, visceral functions and homeostasis. GABA is the most ubiquitous CNS inhibitory neurotransmitter in vertebrates. In the latest decade, the basic attention is paid to analysis of the participation of GABAergic cell populations of the ventrolateral preoptic area (VLPA) of anterior hypothalamus and the Nucleus reticularis pontis oralis (NRPO); these areas are considered as «critical» in the control of nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep (VLPA and NRPO, respectively) [Sherin et al., 1996; Xi et al., 1999; Siegel, 2004]. Such a concept is based on the study of effects of the structure damages or injections of isolated receptor agonists and antagonists; the investigations were carried out only in cats or rats. The goal of the present study is to find out the participation of GABAergic system of the VLPA and the NRPO in the control of wakefulness, NREM and REM sleep in pigeons Columba livia. Such investigations in birds have not been carried out earlier. For an analysis of sleep-wake state and their somatovisceral characteristics all electrophysiological parameters (electroencephalogram, electrooculogram, electromyogram, electrocardiogram, brain and foot skin temperature) were continuously recorded, using a computer system SASH-8800 (USA) and program package. The details of the methods were described earlier [Rashotte et al., 1998]. The stereotaxic coordinates of the preoptic area structures of hypothalamus and the caudal midbrain that take part in the control of wakefulness, NREM and REM sleep in pigeons have been determined for the first time. It has been found that executive GABA-Aergic mechanisms of NREM maintenance are primarily localized in caudal region of the VLPA of hypothalamus. The activation of the VLPA GABA-A receptors by muscimol (30 ng/0.2 mkl) induced an increase in episode durations and total time (TT) of NREM sleep. In contrast, the microinjections of GABA-A receptor antagonist bicuculline (1.0 mkg/0.2 mkl) resulted in an increase in wakefulness and suppression in both phases of sleep. It was found that the VLPA GABA-B receptors do not markedly take part in mechanisms of generation and maintenance of sleep and wakefulness. It is known that neurons of the preoptic area of hypothalamus in pigeons, as well as in cats and rats form efferent connections with the posterior hypothalamus and the brainstem [Berk et al., 1981]. We hypothesize that NREM sleep maintenance in pigeons depends on an increase in activity of VLPA inhibitory GABA-Aergic mechanisms resulted in inactivation of aminergic wake-related arousal networks outside the area. Our investigations indicated that these networks may be localized in the dorso and ventrolateral regions of the caudal substantia grisea centralis (SGC) and in the locus coeruleus (LC): the inactivation by muscimol (0.5 mkg/0.2 mkl) of neuron groups in these areas was accompanied by a considerable increase in the episode duration and TT NREM sleep. This effect may be conditioned by inhibition of aminergic wake-related arousal networks and reciprocal enhancement of GABA-A-ergic mechanisms implicated in the control of NREM sleep in the VLPA and other brain structures. The differences elicited in experiments related to effects of muscimol in the SGC in pigeons (increase in NREM) and cats (increase in REM) [Sastre et al., 1996] indicate specificity of structure functional organization of GABAergic system in these animals. Microinjections of bicuculline (0.5 mkg/0.2 mkl) into the NRPO were found to reduce wakefulness and increase the number of episodes and TT of REM and NREM sleep in pigeons. REM

ISSN 1606-8181

occurred after NREM sleep and its somatic-visceral characteristics correspond to naturally-occurring REM. Hence, depression of GABAA-ergic transmission in the NRPO is one of the activation mechanisms of mesopontine REM-generation networks. Alternatively, the inactivation of neuron groups in the NRPO by muscimol (0.5 mkg/0.2 mkl) was accompanied by a generation of long-lasting wakefulness and a decline in NREM and REM sleep. These effects are appeared to be conditioned by disinhibition of wake-related arousal networks outside the NRPO. Our data indicate marked contribution of GABAA-ergic mechanisms of the hypothalamus and the midbrain to integrative function of the nervous «centres» involved in the control of wakefulness as well as sleep in pigeons. The study was carried out by the Program of DBS of RAS «Integrative mechanisms of wakefulness-sleep cycle regulation».

ISSN 1606-8181