TY - JOUR AB - With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task. AU - Rangel Guerrero, Dámaris K AU - Donnett, James G. AU - Csicsvari, Jozsef L AU - Kovács, Krisztián ID - 5914 IS - 4 JF - eNeuro TI - Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning VL - 5 ER - TY - JOUR AB - During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory inputdriven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity- related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles. AU - Kovács, Krisztián AU - O'Neill, Joseph AU - Schönenberger, Philipp AU - Penttonen, Markku AU - Rangel Guerrero, Dámaris K AU - Csicsvari, Jozsef L ID - 1279 IS - 10 JF - PLoS One TI - Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the hippocampus VL - 11 ER - TY - JOUR AB - CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis. AU - Kovács, Krisztián AU - Steinmann, Myriam AU - Halfon, Olivier AU - Magistretti, Pierre AU - Cardinaux, Jean ID - 1663 IS - 11 JF - Cellular Signalling TI - Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2 VL - 27 ER - TY - JOUR AB - We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks. AU - Lovrics, Anna AU - Gao, Yu AU - Juhász, Bianka AU - Bock, István AU - Byrne, Helen AU - Dinnyés, András AU - Kovács, Krisztián ID - 2004 IS - 11 JF - PLoS One TI - Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord VL - 9 ER - TY - GEN AU - Lovrics, Anna AU - Gao, Yu AU - Juhász, Bianka AU - Bock, István AU - Byrne, Helen M. AU - Dinnyés, András AU - Kovács, Krisztián ID - 9722 TI - Transition probability between TF expression states when Dbx2 inhibits Nkx2.2 ER -