Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

RESEARCH INTERESTS
Respiratory, sleep and metabolic disorders associated with the obstructive sleep apnea syndrome; homeostatic regulation of sleep

RESEARCH SUMMARY
Hypoventilations and apneas characteristic of the Obstructive Sleep Apnea Syndrome (OSAS) occur most frequently and are most severe during the desynchronized, rapid eye movement (REM) stage of sleep. The resulting loss of sleep further exacerbates the disorder. The goals of our research are to understand the pharmacological mechanisms of REM sleep and the accompanying suppression of motoneuronal activity, and to identify the cellular basis of the response to sleep deprivation. Due to the complex nature of sleep, we use complementary electrophysiological in vivo and in vitro techniques, neuroanatomy and molecular biology. In electrophysiological studies, we use of a novel pharmacological model of REM sleep. To characterize the role of different neurotransmitter receptors in sleep-related disorders of breathing, we use in vivo pharmacology and also study changes in receptor mRNA expression in brain regions and single cells involved in the regulation of sleep and breathing. Since OSAS frequently coexists with the metabolic syndrome (hypertension, obesity and diabetes), we also investigate whether oscillation in blood oxygen level (chronic intermittent hypoxia) cause changes in the central and peripheral control of glucose metabolism, such as in type 2 diabetes. In separate studies, we pursue our hypothesis that prolonged wakefulness leads to increased expression of GABA A receptors in the posterior hypothalamus, as region in which increased GABAergic inhibition acts to promote sleep.

RESEARCH TECHNIQUES

Immunohistochemistry and tract-tracing; gene expression analysis; single-cell RT-PCR; intra- and extracellular recording in vivo ; iontophoresis and microinjections; behavioral analysis of sleep/movement in rodents

Selected Publications

Lu, Jackie W. Fenik, Victor B. Branconi, Jennifer L. Mann, Graziella L. Rukhadze, Irma. Kubin, Leszek.: Disinhibition of perifornical hypothalamic neurones activates noradrenergic neurones and blocks pontine carbachol-induced REM sleep-like episodes in rats. Journal of Physiology 582(Pt 2): 553-67, Jul 15 2007.

Rukhadze, Irma. Kubin, Leszek.: Mesopontine cholinergic projections to the hypoglossal motor nucleus. Neuroscience Letters 413(2): 121-5, Feb 14 2007.

Volgin, Denys V. Kubin, Leszek.: Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro. Biochemical & Biophysical Research Communications 353(3): 726-32, Feb 16 2007.

Rukhadze, Irma. Kubin, Leszek.: Differential pontomedullary catecholaminergic projections to hypoglossal motor nucleus and viscerosensory nucleus of the solitary tract. Journal of Chemical Neuroanatomy 33(1): 23-33, Jan 2007.

Kubin, Leszek. Alheid, George F. Zuperku, Edward J. McCrimmon, Donald R.: Central pathways of pulmonary and lower airway vagal afferents. [Review] [143 refs] Journal of Applied Physiology 101(2): 618-27, Aug 2006.

Volgin, Denys V. Kubin, Leszek.: Chronic intermittent hypoxia alters hypothalamic transcription of genes involved in metabolic regulation. Autonomic Neuroscience-Basic & Clinical 126(-127): 93-9, Jun 30 2006.

Fenik, Victor B. Davies, Richard O. Kubin, Leszek.: Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep-like depression of hypoglossal motoneuronal activity. Journal of Sleep Research 14(4): 419-29, Dec 2005.

Fenik, Victor B. Davies, Richard O. Kubin, Leszek.: REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of noradrenergic and serotonergic inputs.[see comment]. American Journal of Respiratory & Critical Care Medicine 172(10): 1322-30, Nov 15 2005.

Lu, Jackie W. Mann, Graziella L. Ross, Richard J. Morrison, Adrian R. Kubin, Leszek.: Differential effect of sleep-wake states on lingual and dorsal neck muscle activity in rats. Respiratory Physiology & Neurobiology 147(2-3): 191-203, Jul 28 2005.

Fenik, Victor B. Ogawa, Hiromasa. Davies, Richard O. Kubin, Leszek.: Carbachol injections into the ventral pontine reticular formation activate locus coeruleus cells in urethane-anesthetized rats. Sleep 28(5): 551-9, May 1 2005.