Research Report GABA A receptor mediated transmission in the thalamic reticular nucleus of rats with genetic absence epilepsy shows regional differences: Functional implications Rezzan Gülhan Aker a , Hazan B. Özyurt a , Hasan R. Yananli a , Yusuf Özgür Çakmak b , Aydan E. Özkaynakçi a , Ümit Sehirli b , Erdinç Saka b , Safiye Çavdar b , Filiz Yılmaz Onat a, ⁎ a Marmara University, School of Medicine, Department of Pharmacology and Clinical Pharmacology, Istanbul 34668, Turkey b Marmara University, School of Medicine, Department of Anatomy, Istanbul 34668, Turkey ARTICLE INFO ABSTRACT Article history: Accepted 28 June 2006 Available online 17 August 2006 The aim of the present study was to investigate the effect of local injections of the GABA A receptor antagonist, bicuculline, into the rostral and caudal parts of the thalamic reticular nucleus (TRN), on the generation of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Spike-and-wave discharges are important in the pathophysiology of absence epilepsy and generated by the cortico-thalamo-cortical pathway, where GABA has a significant role, particularly in the TRN. Artificial cerebrospinal fluid or bicuculline was administered to rostral or caudal parts of TRN of GAERS through a stereotaxically placed guide cannula. Administration of bicuculline produced opposite effects according to the injection site. Administration into the caudal TRN produced statistically significant increases in the duration of spike-and-wave discharges, whereas injections into the rostral TRN produced significant decreases. Correspondingly, distinct patterns of afferent connections have been demonstrated with the wheat-germ-agglutinin horseradish peroxidase (WGA-HRP) retrograde tracing method in control non-epileptic rats and GAERS for the rostral and caudal parts of the TRN. Injection of WGA-HRP tracer showed no detectable difference regarding the rostral and caudal connections between GAERS and Wistar animals. Rostral parts of TRN have thalamic and cortical connections that are primarily motor and limbic whereas for the caudal parts these connections are primarily sensory. Further, the rostral parts receive inputs from the substantia nigra pars reticularis and the ventral pallidum that the caudal part lacks. The extent to which these connectional differences may be responsible for the functional differences demonstrated by the bicucculine injections remains to be explored. © 2006 Elsevier B.V. All rights reserved. Keywords: Bicuculline GAERS Thalamo-cortical connection Rostral TRN Caudal TRN Abbreviations: aCSF, artificial cerebrospinal fluid EEG, electroencephalography GABA, gamma-amino-butyric acid GAERS, Genetic Absence Epilepsy Rats from Strasbourg SWD, spike-and-wave discharge TRN, thalamic reticular nucleus WGA-HRP, wheat-germ agglutinin horse radish peroxidase 1. Introduction Typical childhood absence epilepsy is a form of generalized non-convulsive epilepsy and is characterized by the sudden onset of 3 Hz spike-and-wave discharges (SWD) in the electroencephalogram (EEG), accompanied by behavioral arrest, unresponsiveness and unconsciousness (Neider- meyer, 1996). Many studies have shown that cortico- thalamo-cortical pathways are involved in the generation of SWDs and of absence seizures (Steriade and Deschenes, 1984; BRAIN RESEARCH 1111 (2006) 213 – 221 ⁎ Corresponding author. Fax: +90 216 347 55 94. E-mail address: fonat@marmara.edu.tr (F.Y. Onat). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.06.118 available at www.sciencedirect.com www.elsevier.com/locate/brainres