title: Disinhibition of the intergeniculate leaflet network in the WAG/Rij rat model of absence epilepsy.
abstract: The intergeniculate leaflet (IGL) of the thalamus is a retinorecipient structure implicated in orchestrating circadian rhythmicity. The IGL network is highly GABAergic and consists mainly of neuropeptide Y-synthesising and enkephalinergic neurons. A high density of GFAP-immunoreactive astrocytes has been observed in the IGL, with a probable function in guarding neuronal inhibition. Interestingly, putatively enkephalinergic IGL neurons generate action potentials with an infra-slow oscillatory (ISO) pattern in vivo in urethane anesthetised Wistar rats, under light-on conditions only. Absence epilepsy (AE) is a disease characterised by spike-wave discharges present in the encephalogram, directly caused by hypersynchronous thalamo-cortical oscillations. Many pathologies connected with the arousal system, such as abnormalities in sleep architecture and an insufficient brain sleep-promoting system accompany the epileptic phenotype. We hypothesise that disturbances in the function of biological clock structures, controlling this rhythmic physiological process, may be responsible for the observed pathomechanism. To test this hypothesis, we performed an in vitro patch-clamp study on WAG/Rij rats, a well-validated genetic model of AE, in order to assess dampened GABAergic synaptic transmission in the IGL expressed as a lower IPSC amplitude and reduced sIPSC frequency. Moreover, our in vivo extracellular recordings showed higher firing rate of ISO IGL neurons with an abnormal reaction to a change in constant illumination (maintenance of rhythmic neuronal activity in darkness) in the AE model. Additional immunohistochemical experiments indicated astrogliosis in the area of the IGL, which may partially underlie the observed changes in inhibition. Altogether, the data presented here show for the first time the disinhibition of IGL neurons in a model of AE, thereby proposing the possible involvement of circadian-related brain structures in the epileptic phenotype.
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: lukasz.chrobok@uj.edu.pl.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Chrobok
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: k.palus@uj.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Palus
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: jagoda.jeczmien@doctoral.uj.edu.pl.
authors.forename: Jagoda Stanislawa
authors.initials: JS
authors.lastname: Jeczmien-Lazur
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: anna.chrzanowska@student.uj.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Chrzanowska
authors.affiliation: Faculty of Chemistry, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: kepczyns@chemia.uj.edu.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kepczynski
authors.affiliation: Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. Electronic address: marian.lewandowski@uj.edu.pl.
authors.forename: Marian Henryk
authors.initials: MH
authors.lastname: Lewandowski
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D005829:Geniculate Bodies / Q000473:pathology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D009478:Neuropeptide Y; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: Absence epilepsy; GABA; GFAP; Infra-slow oscillations; Intergeniculate leaflet; Miniature inhibitory postsynaptic currents