Person: ONAT, FİLİZ
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ONAT
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FİLİZ
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Publication Metadata only Topographical connections of the substantia nigra pars reticulata to higher-order thalamic nuclei in the rat(PERGAMON-ELSEVIER SCIENCE LTD, 2012) ONAT, FİLİZ; Gulcebi, Medine Idrizoglu; Ketenci, Sema; Linke, Rudiger; Hacioglu, Husniye; Yanali, Hasan; Veliskova, Jana; Moshe, Solomon L.; Onata, Filiz; Cavdar, SafiyeThe substantia nigra pars reticulata (SNR) is the ventral subdivision of the substantia nigra and contains mostly GABAergic neurons. The present study explores whether the SNR relates to all dorsal thalamic nuclei equally or just to a particular group of nuclei, such as first or higher-order nuclei. Injections of biotinylated dextran amine (BDA) were made into the SNR of 10 male adult rats. The distribution of anterogradely labelled axon terminals in the thalamic nuclei was documented. The projections of the SNR to the thalamic nuclei were exclusively to some motor higher-order, but not to first-order thalamic relays. There were bilateral projections to the ventromedial (VM), parafascicular (PF), centromedian (CM) and paracentral (PC) nuclei and unilateral projections to the centrolateral (CL), mediodorsal (MD) and thalamic reticular nucleus (Rt). Labelled axon terminals in the thalamic nuclei ranged from numerous to sparse in VM, PF, CM, CL, PC, MD and Rt. Further, injections into the SNR along its rostral-caudal axis showed specific topographical connections with the thalamic nuclei. The rostral SNR injections showed labelled axon terminals of VM, PF, CL, PC, CM, MD and Rt. Caudal SNR injections showed labelling of VM, PF, PC, CM and MD. All injections showed labelled axons and terminals in the zona incerta. The nigrothalamic GABAergic neurons can be regarded as an important system for the regulation of motor activities. The SNR is in a position to influence large areas of the neocortex by modulating some of the motor higher-order thalamic nuclei directly or indirectly via Rt. (C) 2011 Elsevier Inc. All rights reserved.Publication Open Access Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo(ELSEVIER SCIENCE BV, 2014-09) ONAT, FİLİZ; Taylor, Hannah; Schmiedt, Joscha T.; Carcak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Regis C.; Leresche, Nathalie; Crunelli, Vincenzo; David, FrancoisBackground: The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. New method and results: We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca2+ channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. Comparison with existing methods: This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. Conclusions: The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on lasermodulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations. (C) 2014 Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).Publication Metadata only Changes in intracellular protein expression in cortex., thalamus and hippocampus in a genetic rat model of absence epilepsy(PERGAMON-ELSEVIER SCIENCE LTD, 2011) OGAN, AYŞE; Danis, Ozkan; Demir, Serap; Gunel, Aslihan; Aker, Rezzan Gulhan; Gulcebi, Medine; Onat, Filiz; Ogan, AyseEpilepsy is a chronic disorder characterized by repeated seizures resulting from abnormal activation of neurons in the brain. Although mutations in genes related to Na+, K+, Ca2+ channels have been defined, few studies show intracellular protein changes. We have used proteomics to investigate the expression of soluble proteins in a genetic rat model of absence epilepsy Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The advantage of this technique is its high throughput quantitative and qualitative detection of all proteins with their post-translational modifications at a given time. The parietal cortex and thalamus, which are the regions responsible for the generation of absence seizures, and the hippocampus, which is not involved in this activity, were dissected from GAERS and from non-epileptic control rat brains. Proteins from each tissue sample were isolated and separated by two-dimensional gel electrophoresis. Spots that showed significantly different levels of expression between controls and GAERS were identified by nano LC-ESI-MS/MS. Identified proteins were: ATP synthase subunit delta and the 14-3-3 zeta isoform in parietal cortex; myelin basic protein and macrophage migration inhibitory factor in thalamus; and macrophage migration inhibitory factor and 0-beta 2 globulin in hippocampus. All protein expressions were up-regulated in GAERS except 0-beta globulin. These soluble proteins are related to energy generation, signal transduction, inflammatory processes and membrane conductance. These results indicate that not only membrane proteins but also cytoplasmic proteins may take place in the pathophysiology and can be therapeutic targets in absence epilepsy. (C) 2011 Elsevier Inc. All rights reserved.Publication Metadata only Do the quantitative relationships of synaptic junctions and terminals in the thalamus of genetic absence epilepsy rats from Strasbourg (GAERS) differ from those in normal control Wistar rats(SPRINGER-VERLAG ITALIA SRL, 2012) ONAT, FİLİZ; Cavdar, Safiye; Hacioglu, Husniye; Dogukan, Secan Y.; Onat, FilizAbnormal functional properties of the thalamocortical connections were reported in the absence of epilepsy. The present study compares the ratios of terminals (`RL'-round vesicles, large terminals, 'RS'-round vesicles, small terminals and 'F'-flattened vesicles) and synapse in three first-order (ventrobasal, lateral geniculate and anteroventral) and in three higher-order (posterior, lateral posterior and mediodorsal) thalamic nuclei of genetic absence epilepsy rats from Strasbourg (GAERS) with our earlier quantitative studies of normal Wistar rats to show whether quantitative differences were present in GAERS as compared to Wistar rat. Rats were perfused transcardially, the brains were removed and cut as 300 lmcoronal sections. Parts of the six thalamic nuclei were removed for routine electron microscopy and GABA immunocytochemistry. Twenty photographs from each section at 20,0009 magnification were taken, and the terminals were identified as RL, RS or F. (1) In normal Wistar rats (as in cats), the proportion of driver terminals (RL) and synapses is lower in higherorder than in first-order thalamic nuclei, but this difference is not present in GAERS animals. (2) The proportions of RS terminals and synapses for each thalamic nucleus showed no significant differences between GAERS and Wistar rats for any of the thalamic nuclei. (3) In GAERS, the proportion of inhibitory F terminals and synapses was significantly high in the VB and low in the LP thalamic nucleus. These abnormal ratios in the GAERS may be the cause of the spike-and-wave discharges of absence seizures or may represent a compensatory response of the thalamocortical circuitry to the absence seizures.Publication Open Access The effect of prenatal and postnatal caffeine exposure on pentylentetrazole induced seizures in the non-epileptic and epileptic offsprings(2019-11-01) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ONAT, FİLİZ; YAVUZ M., Albayrak N., Ozgur M., Oglu M., Cavdar S., Onat F.Caffeine, a central nervous system stimulant, has been reported to modulate seizure activity in various studies. In this study the effects of caffeine exposure on the pentylenetetrazole (PTZ) induced seizure thresholds and seizure stages in the Wistar and genetic absence epilepsy model offsprings were examined. Adult female and male Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) consumed caffeine dissolved in water (0.3 g/L) before conception, during the gestational periods and lactation period whereas control groups of each strain received tap water. All offsprings at postnatal day 30 (PN30) subjected to 70 mg/kg of PTZ were evaluated in terms of overall seizure stages, the latency to the first generalized seizure and the c-Fos protein activity in the brain regions of somatosensorial cortex (SSCx), reticular thalamic nucleus (Rt), ventrobasal thalamus (VB), centromedial nucleus (CM) and lateral geniculate nucleus (LGN). The Wistar caffeine group had significantly shorter latency to the first generalized seizure (1.53 +/- 0.49 min) comparing to the Wistar control offsprings (3.40 +/- 0.68 min). GAERS caffeine group (6.52 +/- 2.48 min) showed significantly longer latency comparing to Wistar caffeine group (1.53 +/- 0.49 min). Although statistically not significant, GAERS caffeine group showed a longer latency comparing to the GAERS control group (4.71 +/- 1.82 min). In all regions of SSCx, Rt, VB, CM and LGN, GAERS caffeine group had lower c-Fos protein expression comparing to the GAERS control group (p < 0.05). Wistar caffeine rats had lower expression of c-Fos protein comparing to the Wistar control group only in SSCx. In CM, GAERS rats expressed lower c-Fos protein comparing to the Wistar control (p < 0.05). In conclusion differential effects of caffeine in the seizure modulation may involve c-Fos protein activity-dependent protection mechanisms.