August 2014
Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation.
In the Nature Communications edition of August 2014, we present our study on the complete conditional and time-controlled silencing of the 'funny' current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA) (read on), which we conducted in cooperation with Pietro Mesirca and Matteo Mangoni from the INSERM unit U661 of the University of Montpellier.
August 2013
Adenosine receptor antagonists including caffeine alter fetal brain development in mice.
In collaboration with scientists from Christophe Bernard's research group in Marseille, we recently investigated the effect of caffeine and adenosine receptor antagonists on neuronal development (read on for the editor's summary in Science Translational Magazine, Sci Transl Med 7 August 2013: Vol. 5, Issue 197, p. 197ra104).
July 2013
Priority Programme “Resolving and Manipulating Neuronal Networks in the Mammalian Brain – from Correlative to Causal Analysis” (SPP 1665).
A new Priority Program entitled "Resolving and Manipulating Neuronal Networks in the Mammalian Brain – from Correlative to Causal Analysis" (SPP 1665) was recently successfully evaluated by the Deutsche Forschungsgemeinschaft (DFG, German Research Council). The goal of this program, whose initial funding period is three years, is aimed at identifying causal relationships between the activity of single neurons within networks and behavior by taking advantage of recently developed new recording and imaging techniques, as well as neurotechnology and optogenetic tools. In cooperation with Dr. Anton Sirota (Tübingen), our group will focus on promoting the high-resolution characterization of functional connectivity and behavior in healthy and transgenic mice from the neonatal period through adulthood. To be able to study the role of early network activity in the developing mouse brain, we will collaborate with Professor Krautschneider's group at the Technische Universität Hamburg-Harburg on the development and building of miniaturized recording devices.
June 2013
Differential regulation of AMPK activation in leptin- and creatine-deficient mice.
In a study conducted by Malte Stockebrand et al., a follow-up to our previous work published in Human Molecular Genetics (see below), which recently appeared in the FASEB J., we investigated the leptin-dependent AMP-activated protein kinase (AMPK) regulation in AGAT- and leptin-deficient (d/d ob/ob) mice and showed that preserved leptin sensitivity is required for AMPK-based prevention/treatment strategies of metabolic syndrome (read on).

June 2013
Spatial memory tasks in rodents: what do they model?
In a review that appeared in the June issue of Cell Tissue Res. 2013, Fabio Morellini reviews the literature on the analysis of spatial learning and memory in rodents commonly used to investigate the mechanisms underlying certain forms of human cognition and to model their dysfunction in neuropsychiatric and neurodegenerative diseases. The aim of this review is to describe the experimental approaches that are used for the study of spatial memory in rats and mice, and the manner in which they can be interpreted in terms of general memory functions. After an introduction to the classification of memory into various categories and the respective underlying neuroanatomical substrates, Fabio explains the concept of spatial memory and its measurement in rats and mice by analyzing their navigation strategies. Subsequently, he describes the most common paradigms for spatial memory assessment with a specific focus on methodological issues relevant for the correct interpretation of the results in terms of cognitive function. Finally, he presents recent advances in the use of spatial memory tasks to investigate episodic-like memory in mice (read on).

June 2013
Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear.
In a recent study published in PNAS, the authors, Raffael Kalisch, Jan Haaker (Institut fuer Systemische Neurowissenschaften, UKE), and Fabio Morellini et al. found that dopamine-dependent boosting of extinction memory consolidation might be a promising approach to improving anxiety therapy. One of the biggest problems in the treatment of fear or anxiety disorders is the relapse that frequently occurs after an initially successful therapy. Therefore, Fabio Morellini and Kolja Meier tested the hypothesis of whether the dopamine precursor L-dopa facilitates the extinction of fear-conditioned responses in mice. Their data indicate that post-extinction administration of L-dopa makes extinction memories context-independent, thus strongly reducing the return of fear. The morphological quantification of neurons positive for the immediate early gene c-fos indicated that reduced fear was accompanied by decreased activation of the amygdala and enhanced activation of the ventromedial prefrontal cortex. The results were translated into a human model in which fMRI and behavioral analyses were performed in subjects undergoing an extinction protocol for conditioned fear memories. In conclusion, the present study suggests that the dopaminergic system is a key player in modulating the extinction of fear in mice and humans. Finally, the results indicate that post-extinction administration of L-dopa is a simple and safe pharmacological method for the extinction of fear. Raffael Kalisch (Institut fuer Systemische Neurowissenschaften, UKE) initiated the project and performed the behavioral and fMRI experiments in humans (read on).

January 2013
Mice create what-where-when hippocampus-dependent memories of unique experiences.
In a recent study published in Journal of Neuroscience, Fabio Morellini and Laetitia Fellini investigated how mice process complex "what-where-when" information, providing first experimental evidence that mice have episodic-like memories. Using an ecologically relevant paradigm for spontaneous learning and memory, they show that mice modulate their behavior based on the what, where, and when components of past unique episodes, specifically on previous encounters of conspecifics at a defined location and at a specific time of the day. This study also demonstrates that learning during this paradigm activated Arc/Arg3.1 mRNA expression in the hippocampus, and that stereotactic injection of anisomycin into this region impairs memory consolidation. Hippocampus-dependent episodic-like memories of single experiences are thus spontaneously created in mice (read on (pdf)).

January 2013
L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.
In collaboration with scientists from The Netherlands and Belgium, we recently generated and metabolically characterized AGAT-deficient mice that were devoid of Cr and its precursor GuA, and found that these mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels, and enhanced glucose tolerance. Our study, which appeared in Human Molecular Genetics, shows that L-arginine:glycine amidinotransferase (AGAT) deficiency protects from metabolic syndrome. Furthermore, we show that Cr deficiency completely protects from the development of metabolic syndrome caused by diet-induced obesity. This genetic mouse model study provides valuable insight into metabolic changes in Cr deficiency syndromes and reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus (read on (pdf)).

December 2012
Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake.
Together with scientists from the Netherlands, we investigated the consequences of a systemic depletion of creatine in mice deficient in L-arginine:glycine amidino transferase (AGAT-/-) (see above), which catalyses the first step of Cr biosynthesis. Systemic creatine depletion resulted in mitochondrial dysfunction and intracellular energy deficiency, as well as in structural and physiological abnormalities. Oral Cr administration led to a rapid uptake in skeletal muscle and reversed all muscle abnormalities. One of the results of this study shows that a shift from creatine deficient to normal in AGAT-/- mice was simply achieved by dietary creatine supplementation (read on (pdf)).
July 11, 2011
Recently, the Deutsche Forschungsgemeinschaft (German Research Council) approved a proposal for a new SFB (Collaborative Research Center) entitled "Multi-site brain communication" (see also press release by the UKE). This multidisciplinary approach to the study of functional brain connectivity, which was initiated by the coordinators Prof. Dr. Andreas Engel and Prof. Dr. Christian Gerloff (University Medical Center Hamburg-Eppendorf), includes research teams of the Universities of Hamburg, Lübeck, and Oldenburg.
The aim of our project within this SFB initiative (SFB 936) is to investigate the molecular, cellular, and network mechanisms underlying information transfer in the entorhinal cortex-hippocampus circuitry during memory consolidation and retrieval. The focus of this project, which is headed by Fabio Morellini and Dirk Isbrandt, will be to find out how neuronal and network activities within and between the EC and hippocampus regulate memory consolidation and retrieval, and whether these functions are determined by the intrinsic resonance properties of specific neuronal populations.