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Laboratory of Cerebral Cortex Research
 
Short general presentation
The ultimate aim of this laboratory is to understand how information is encoded in specific spatiotemporal activity patterns and structural configurations at the circuit, cellular, and molecular levels in the hippocampus, thereby enabling the process of memory. A major task is to find the neuronal codes of internal representations of memory items and the mapping rules between the levels of gene expression/proteins synthesis and the level of cognitive processing. Novel combinations of approaches, including multiple single-cell recording technology, patch-clamp electrophysiology, neuroanatomy/neurochemistry at the cellular and subcellular levels, and computational models are employed to test specific hypotheses about that mapping process (such as local circuit anatomy and activity-dependent short-term and long-term synaptic plasticity). Collaborations within the Institute allows the group to also incorporate gene targeting methods and behavioral learning/memory tests in their methodological repertoire.
Targeted genetic engineering: Research using in vivo and in vitro techniques has identified a range of phenomena that are suspected of playing a key role in the encoding and initial storage of information.  These include long-term potentiation (LTP) and oscillatory neural activity, both being under the control of local GABAergic inhibition. Targeted genetic manipulation (including novel, drug-inducible gene-targeting techniques) are being used to generate mouse lines with a GABAergic system that has been modified in their receptor expression patterns (e.g. CB1 cannabinoid, 5-HT3, and nicotinic alpha7 receptors). The mechanisms behind any changes in the behaviour of these animals (e.g. learning and memory, anxiety, susceptibility to epilepsy) will be investigated at the network, cellular and molecular levels.
GABAergic inhibitory interneurons are known to play a major role in the generation of rhythmic (both in the theta and gamma range) and intermittent synchronous network events. Earlier work of this laboratory provided evidence that the morphological and neurochemical diversity of interneuron types is associated with distinct functional roles, i.e. perisomatic inhibitory cells control (and synchronize) the output of principal cell assemblies, whereas dendritic inhibition regulates the efficacy and plasticity of glutamatergic synaptic inputs. A third category of interneurons specialized to innervate (and synchronize) other inhibitory neurons (interneuron-selecive interneurons, or IS cells). The Freund laboratory demonstrated that local collaterals of hippocampo-septal GABAergic neurons are very extensive, and selectively innervate other interneurons, i.e. they also belong to the IS cell category. They are in an ideal position to align in phase the firing of GABAergic pacemaker units of the medial septum, as well as their target interneurons in the hippocampus. A synthesis of data about perisomatic inhibitory neurons led to the hypothesis that CCK-containing interneurons, expressing presynaptic CB1 receptors, play a key role in anxiety-like behaviours. Genetic or pharmacological interruption of CB1 receptor-mediated actions leads to anxiety, whereas blocking the new cannabinoid-sensitive receptors on glutamatergic terminals has an anxiolytic effect.  The particular expertise and history of this laboratory in the morpho-functional analysis of hippocampal circuits represent sufficient ground for a continued effort - involving new molecular and behavioural approaches - to unravel the cellular and molecular bases of network operations involved in oscillations or different functional brain states, as well as in pathological activity including epilepsy and anxiety.
 
We demonstrated that the neurochemical characteristics and connectivity of different cell types determine their vulnerability in epilepsy and ischemia. Examination of the synaptic reorganization of dentate gyrus and cornu Ammonis in temporal lobe epileptic humans as well as in animal models revealed that, in addition to the excitatory pathways, interneurons are also able to sprout. Increased perisomatic inhibitory input was found on dentate granule cells which may participate in the hypersynchronization of the dentate gyrus enhancing the generation or maintenance of seizures. Damage to dendritic interneurons, and the presumed poor synchrony in their activity due to the loss of interneuron-selective cells, may result in an impaired dendritic inhibition and an enhanced plasticity of excitatory inputs. Abnormal inhibitory connections were observed also in the epileptic cornu Ammonis, dendritic inhibitory cells terminated on other interneurons in higher proportions then in controls. These changes were present both in sclerotic and  non-sclerotic hippocampi, showing that epileptic seizures are accompained by a reviring of the network regardless of the presence or absence of principal cell loss.
 
Mission statement
The laboratory has been focusing on the normal and pathological (epileptic, ischemic) 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. An expanding new direction of research is related to the role of endocannabinoid signaling in the activity-dependent modulation of GABAergic and glutamatergic transmission, and its involvement in anxiety-like behaviour.
 
Members of the Laboratory

 

Laboratory of Cerebral Cortex Research

Name Organization Status Room Extension Direct no. Fax


Freund, Tamás Dr.   Laboratory of Cerebral Cortex Research    406  244  2109411  2109412 
 
Barth, Albert Miklós   Laboratory of Cerebral Cortex Research    413  214     
 
Buzsáki, György Prof.   Laboratory of Cerebral Cortex Research    1. emeleti tárgyaló  390     
 
Cserép, Csaba Dr.   Laboratory of Cerebral Cortex Research    403  241    2109412 
 
Domonkos, Andor   Laboratory of Cerebral Cortex Research    413, 413/a  188, 214     
 
Gulyás, Attila Dr.   Laboratory of Cerebral Cortex Research    408  246  2109413  2109412 
 
Jelitai, Márta PhD   Laboratory of Cerebral Cortex Research    504  189     
 
Káli, Szabolcs Dr.   Laboratory of Cerebral Cortex Research    408  246  2109413  2109412 
 
Kohus, Zsolt   Laboratory of Cerebral Cortex Research    408  246     
 
Lopez, Diego   Laboratory of Cerebral Cortex Research           
 
Maglóczky, Zsófia Dr.   Laboratory of Cerebral Cortex Research    402/a  240  2109415  2109412 
 
Nyíri, Gábor Dr.   Laboratory of Cerebral Cortex Research    401/A  190    2109412 
 
Papp, Péter   Laboratory of Cerebral Cortex Research    402  240     
 
Tresóné Takács, Virág   Laboratory of Cerebral Cortex Research    403  241     
 
Varga, Viktor Lajos Dr.   Laboratory of Cerebral Cortex Research    411  159    2109412 
 
Schlingloff, Dániel   Laboratory of Cerebral Cortex Research    408  246     
 
Sós, Katalin Eszter   Laboratory of Cerebral Cortex Research    403  241     
 
Berki, Péter   Laboratory of Cerebral Cortex Research    408  246, 265     
 
Goda, Győző   Laboratory of Cerebral Cortex Research    411  249    2109412 
 
Kézdi, Dorottya   Laboratory of Cerebral Cortex Research    404  242     
 
Lengyel, Zoltánné   Laboratory of Cerebral Cortex Research    404/a  242, 243, 247    2109412 
 
Simon, Emőke   Laboratory of Cerebral Cortex Research    409  247    2109412 
 
Iványi, Katalin   Laboratory of Cerebral Cortex Research    407  245  2109411  2109412 
 
Bíró, Izolda   Laboratory of Cerebral Cortex Research    402  240     
 
Friedrich, Péter   Laboratory of Cerebral Cortex Research    408  246     
 
Gémes, Dániel   Laboratory of Cerebral Cortex Research    407  246,214     
 
Hajnal, Benjámin   Laboratory of Cerebral Cortex Research    408,413  246     
 
Heiner, Vivien   Laboratory of Cerebral Cortex Research    408  246     
 
Hild, András   Laboratory of Cerebral Cortex Research    408  354     
 
Klein, Kristóf   Laboratory of Cerebral Cortex Research    Varga V.       
 
Mayer, Márton   Laboratory of Cerebral Cortex Research    403  241     
 
Nagy, Ágoston   Laboratory of Cerebral Cortex Research    402  240     
 
Nagy, Dávid Gergely   Laboratory of Cerebral Cortex Research    408  246     
 
Pásztor, Zsófia   Laboratory of Cerebral Cortex Research    401/a  190     
 
Pósfai, Balázs   Laboratory of Cerebral Cortex Research    401/a  190     
 
Rákóczi, Dorina   Laboratory of Cerebral Cortex Research    409  246     
 
Sáray, Sára   Laboratory of Cerebral Cortex Research    413  187     
 
Soós, Bettina   Laboratory of Cerebral Cortex Research    413  187     
 
Szocsics, Péter   Laboratory of Cerebral Cortex Research    402  240     
 
Szőnyi, András   Laboratory of Cerebral Cortex Research    403  241     
 
Tar, Luca   Laboratory of Cerebral Cortex Research    413  187     
 
Tóth, Estilla Zsófia   Laboratory of Cerebral Cortex Research    402  240     
 
Verebélyi, Dorottya   Laboratory of Cerebral Cortex Research    413/a  188     
 
Vidosits, András   Laboratory of Cerebral Cortex Research    408  246     
 
Vig, Georgina   Laboratory of Cerebral Cortex Research    402  240     
 
Elektronmikroszkóp, szoba IV.   Laboratory of Cerebral Cortex Research    412  212     
 
Kriczky, Nándor   Laboratory of Cerebral Cortex Research    408, 612  246, 265     
 
Metsző,   Laboratory of Cerebral Cortex Research    404/A  243     
 
Mikroszkóp, szoba   Laboratory of Cerebral Cortex Research    403  241