Expertise and current research performed: CR5 MTA KOKI is the only research institution in Hungary dedicated exclusively to medical research. Its activity focuses on basic biomedical research, primarily in the field of neuroscience, including studies on neurotransmission, learning and memory, behaviour, ischaemic and epileptic brain damage, control of hormone secretion. The research teams of the Institute employ multidisciplinary approaches: traditional methodologies (e.g. anatomy, electrophysiology, neurochemistry and pharmacology) combined with novel approaches in cellular and molecular biology, as well as with patch clamp and calcium imaging techniques. The laboratory of Cerebral Cortex has been focusing on the normal and pathological (epileptic) activity of cortical networks, with particular attention to the generation of behaviour-dependent population discharge patterns (Theta and Gamma oscillations, hippocampal sharp waves). Anatomical, in vitro and in vivo electrophysiological, pharmacological and molecular techniques and modeling are combined to elucidate the functional roles of inhibitory cell types in the control of population synchrony and synaptic plasticity in the hippocampus, their local and subcortical modulation via selective afferent pathways (GABAergic and cholinergic septal, as well as serotonergic raphe input) and pre- or postsynaptic receptors. The group collaborates with the following teams:

-          with the Neurology Team of National Institute of Psychiatry and Neurology for pre- and postoperative evaluation of patients

-          with the Neurosurgery Team of National Institute of Neurosurgery for the operation of patients, management of the biopsy samples and positioning of the electrodes for interoperative recordings

-          with the Research Institute of Psychology, Hungarian Academy of Sciences for electrophysiological recordings and data evaluation

Facilities/Equipment: The institute has more than 70 laboratories, facilities for tissue culturing, genotyping, isotope and hormone measurements, computer hub, library, and an animal facility with SPF and conventional levels. 2 photon- and confocal-laser microscopes, several electrophysiological setups for in vivo and in vitro recordings, 2 electronmicroscopes, fully equipped molecular biology and transgenic units and laboratories for behavioural studies.

Personnel involved in the project

Principal investigator: F. Tamás Freund (M). PhD, DSc. Director of the Institute, Member of the Hungarian Academy of Sciences. He has been studying the functional architecture of the hippocampus, neocortex and related subcortical structures since 1978. Prof. Freund co-ordinates a multidisciplinary team from molecular to behavioural levels studying the functional roles and network mechanisms of normal and pathological (e.g. epileptic) activity patterns. In this proposal Professor Freund’s group brings anatomical and electrophysiological expertise in human as well as animal tissues, and they propose to investigate the multiple facets of epileptic reorganization of cortical networks.

Istvan Ulbert (M). MD, PhD. Senior Research Scientist at the IP HAS in Budapest. He received the M.Sc degree in Electrical Engineering from the Technical Univ. in 1988, the M.D. degree from the Semmelweis Univ. in 1997 and the PhD degree in Neuroscience in 2002. His main interests: development of implantable cortical biosensors and analysis tools; investigation of intracortical generators of evoked potentials and epilepsy. Zsofia Magloczky (F). PhD. Dr. Maglóczky received her PhD degree in Neurobiology in 1996. She is leading the immunocytochemical and electron microscopic investigations. She is a Senior Research Scientist at the MTA KOKI since 1996. Her main interest is the investigation of the hippocampal and cortical reorganization in the temporal and extratemporal lobe epilepsies in human patients and in animal models of epilepsy. Peter Halasz (M). MD, PhD, DSc. Prof. Halász is the leading neurologist in the group. He is the program director of the Comp-rehensive Epilepsy Center in the NIPN since 2001. He was chairman of the Neurology Dept. Semmelweis University. His main interest is the patho-mechanism of epilepsy and sleep disorders in humans. Prof. Halasz is leading the team identifying patients for surgery, providing diagnosis details, and following the symptoms after surgery. Lorand Eross (M). MD. Dr. Erőss is the leading neurosurgeon in the group, graduated at the Semmelweis Medical University, Budapest in 1990. He started his neurosurgical internship in 1991. Because of his interest in functional neurosurgery, he qualified first as a neurologist in 1995, and then in neurosurgery in 2000. He is responsible for the Functional Neurosurgery Program at the National Intstitute of Neurosurgery in Budapest. Lucia Wittner (F). PhD. Dr. Wittner is a young postdoctoral fellow who just began in vitro recordings in the field of epilepsy. She has experience in the anatomical investigation of the epileptic human tissues (interneuronal networks). Also she carried out correlated anatomical examinations of in vitro and in vivo recorded and intracellularly filled neurons. She will carry out studies of the GABAergic and glutamatergic transmission in epileptic tissues. Zsofia Clemens (F). PhD. Dr. Clemens is a young postdoctoral fellow with research experience in clinical epilepsy and sleep research. Her main research area is related to interactions between sleep and epilepsy, interictal epileptic discharges and intracranial recordings is patients undergoing presurgical evaluations. In 2004 she received the Young Investigators’ Award from the European Sleep Research Society. Edit Papp (F). PhD. Dr. Edit Papp has a long experience in the cellular and subcellular localization of transmistters and receptors in complex integrative centres of the brain. She is going to be involved in the functional anatomical studies of the distribution of receptors in animal models of epilepsy and human epileptic tissues. Kinga Tóth (F). Junior research fellow, she received her MSc degree in 2005. As a student research assistant she participated in the examination of the human epileptic hippocampus. She is going to be involved in fine structural characterization of the synaptic reorganization in models of epilepsy and in human epileptic tissues.

Recent relevant publications/patents

1.       Wittner L., Erőss L., Czirjak S., Halász P., Freund T.F., Maglóczky Z. (2005) Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus. Brain 128: 138-152.

2.       Maglóczky Z., Freund T.F. (2005) Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci. 28: 334-340.

3.       Ulbert I., Magloczky Zs., Eross L., Czirjak S., Vajda J., Bognar L., Toth S., Szabo Z., Halasz P., Fabo D., Halgren E., Freund T.F., Karmos G. (2004) In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy. Exp Neurol. 187:310-318.

4.       Maglóczky Zs., Wittner L., Borhegyi Zs., Halász P., Vajda J., Czirják S. and Freund T.F. (2000) Changes in the distribution and connectivity of interneurons in the epileptic human dentate gyrus. Neuroscience 96: 7-25.

5.       Gulyás A.I., Miles R., Sík A., Tóth K., Tamamaki N. and Freund T.F. (1993) Hippocampal pyramidal cells excite inhibitory neurons via single release sites. Nature 366: 683-687.