@article{RiveroSeltenSichetal.2015, author = {Rivero, O and Selten, MM and Sich, S and Popp, S and Bacmeister, L and Amendola, E and Negwer, M and Schubert, D and Proft, F and Kiser, D and Schmitt, AG and Gross, C and Kolk, SM and Strekalova, T and van den Hove, D and Resink, TJ and Kasir, N Nadif and Lesch, KP}, title = {Cadherin-13, a risk gene for ADHD and comorbid disorders, impacts GABAergic function in hippocampus and cognition}, series = {Translational Psychiatry}, volume = {5}, journal = {Translational Psychiatry}, number = {e655}, doi = {10.1038/tp.2015.152}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145218}, year = {2015}, abstract = {Cadherin-13 (CDH13), a unique glycosylphosphatidylinositol-anchored member of the cadherin family of cell adhesion molecules, has been identified as a risk gene for attention-deficit/hyperactivity disorder (ADHD) and various comorbid neurodevelopmental and psychiatric conditions, including depression, substance abuse, autism spectrum disorder and violent behavior, while the mechanism whereby CDH13 dysfunction influences pathogenesis of neuropsychiatric disorders remains elusive. Here we explored the potential role of CDH13 in the inhibitory modulation of brain activity by investigating synaptic function of GABAergic interneurons. Cellular and subcellular distribution of CDH13 was analyzed in the murine hippocampus and a mouse model with a targeted inactivation of Cdh13 was generated to evaluate how CDH13 modulates synaptic activity of hippocampal interneurons and behavioral domains related to psychopathologic (endo) phenotypes. We show that CDH13 expression in the cornu ammonis (CA) region of the hippocampus is confined to distinct classes of interneurons. Specifically, CDH13 is expressed by numerous parvalbumin and somatostatin-expressing interneurons located in the stratum oriens, where it localizes to both the soma and the presynaptic compartment. Cdh13\(^{-/-}\) mice show an increase in basal inhibitory, but not excitatory, synaptic transmission in CA1 pyramidal neurons. Associated with these alterations in hippocampal function, Cdh13\(^{-/-}\) mice display deficits in learning and memory. Taken together, our results indicate that CDH13 is a negative regulator of inhibitory synapses in the hippocampus, and provide insights into how CDH13 dysfunction may contribute to the excitatory/inhibitory imbalance observed in neurodevelopmental disorders, such as ADHD and autism.}, language = {en} } @article{PetrasekProkopovaSladeketal.2014, author = {Petrasek, Tomas and Prokopova, Iva and Sladek, Martin and Weissova, Kamila and Vojtechova, Iveta and Bahnik, Stepan and Zemanova, Anna and Sch{\"o}nig, Kai and Berger, Stefan and Tews, Bjoern and Bartsch, Dusan and Schwab, Martin E. and Sumova, Alena and Stuchlik, Ales}, title = {Nogo-A-deficient transgenic rats show deficits in higher cognitive functions, decreased anxiety, and altered circadian activity patterns}, series = {Frontiers in Behavioral Neuroscience}, volume = {8}, journal = {Frontiers in Behavioral Neuroscience}, number = {90}, doi = {10.3389/fnbeh.2014.00090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117073}, year = {2014}, abstract = {Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity, and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A knockout rats and their circadian period (tau) did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality, and activity patterns.}, language = {en} } @article{MaiellaroLohseKitteetal.2016, author = {Maiellaro, Isabella and Lohse, Martin J. and Kitte, Robert J. and Calebiro, Davide}, title = {cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons}, series = {Cell Reports}, volume = {17}, journal = {Cell Reports}, number = {5}, doi = {10.1016/j.celrep.2016.09.090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-162324}, pages = {1238-1246}, year = {2016}, abstract = {The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons.}, language = {en} } @article{GrobHeinigGruebeletal.2021, author = {Grob, Robin and Heinig, Niklas and Gr{\"u}bel, Kornelia and R{\"o}ssler, Wolfgang and Fleischmann, Pauline N.}, title = {Sex-specific and caste-specific brain adaptations related to spatial orientation in Cataglyphis ants}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, number = {18}, doi = {10.1002/cne.25221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257299}, pages = {3882-3892}, year = {2021}, abstract = {Cataglyphis desert ants are charismatic central place foragers. After long-ranging foraging trips, individual workers navigate back to their nest relying mostly on visual cues. The reproductive caste faces other orientation challenges, i.e. mate finding and colony foundation. Here we compare brain structures involved in spatial orientation of Cataglyphis nodus males, gynes, and foragers by quantifying relative neuropil volumes associated with two visual pathways, and numbers and volumes of antennal lobe (AL) olfactory glomeruli. Furthermore, we determined absolute numbers of synaptic complexes in visual and olfactory regions of the mushroom bodies (MB) and a major relay station of the sky-compass pathway to the central complex (CX). Both female castes possess enlarged brain centers for sensory integration, learning, and memory, reflected in voluminous MBs containing about twice the numbers of synaptic complexes compared with males. Overall, male brains are smaller compared with both female castes, but the relative volumes of the optic lobes and CX are enlarged indicating the importance of visual guidance during innate behaviors. Male ALs contain greatly enlarged glomeruli, presumably involved in sex-pheromone detection. Adaptations at both the neuropil and synaptic levels clearly reflect differences in sex-specific and caste-specific demands for sensory processing and behavioral plasticity underlying spatial orientation.}, language = {en} } @article{FalibeneRocesRoessler2015, author = {Falibene, Augustina and Roces, Flavio and R{\"o}ssler, Wolfgang}, title = {Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants}, series = {Frontiers in Behavioural Neuroscience}, volume = {9}, journal = {Frontiers in Behavioural Neuroscience}, number = {84}, doi = {10.3389/fnbeh.2015.00084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148763}, year = {2015}, abstract = {Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MB) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning when ants still showed plant avoidance MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.}, language = {en} } @article{FalibeneRocesRoessler2015, author = {Falibene, Agustina and Roces, Flavio and R{\"o}ssler, Wolfgang}, title = {Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants}, series = {Frontiers in Behavioral Neuroscience}, volume = {9}, journal = {Frontiers in Behavioral Neuroscience}, number = {84}, doi = {10.3389/fnbeh.2015.00084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125522}, year = {2015}, abstract = {Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MBs) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning—when ants still showed plant avoidance—MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.}, language = {en} } @article{BusseStrotmannStreckeretal.2014, author = {Busse, Kathy and Strotmann, Rainer and Strecker, Karl and Wegner, Florian and Devanathan, Vasudharani and Gohla, Antje and Sch{\"o}neberg, Torsten and Schwarz, Johannes}, title = {Adaptive Gene Regulation in the Striatum of RGS9-Deficient Mice}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {3}, doi = {10.1371/journal.pone.0092605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117048}, pages = {e92605}, year = {2014}, abstract = {Background: RGS9-deficient mice show drug-induced dyskinesia but normal locomotor activity under unchallenged conditions. Results: Genes related to Ca2+ signaling and their functions were regulated in RGS9-deficient mice. Conclusion: Changes in Ca2+ signaling that compensate for RGS9 loss-of-function can explain the normal locomotor activity in RGS9-deficient mice under unchallenged conditions. Significance: Identified signaling components may represent novel targets in antidyskinetic therapy. The long splice variant of the regulator of G-protein signaling 9 (RGS9-2) is enriched in striatal medium spiny neurons and dampens dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its overexpression prevents drug-induced dyskinesia. Other animal models of drug-induced dyskinesia rather pointed towards overactivity of dopamine receptor-mediated signaling. To evaluate changes in signaling pathways mRNA expression levels were determined and compared in wild-type and RGS9-deficient mice. Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9-deficient mice, while several genes related to Ca2+ signaling and long-term depression were differentially expressed when compared to wild type animals. Detailed investigations at the protein level revealed hyperphosphorylation of DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell patch clamp recordings showed that spontaneous synaptic events are increased (frequency and size) in RGS9-deficient mice while long-term depression is reduced in acute brain slices. These changes are compatible with a Ca2+-induced potentiation of dopamine receptor signaling which may contribute to the drug-induced dyskinesia in RGS9-deficient mice.}, language = {en} } @article{AndreskaLueningschroerSendtner2020, author = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Sendtner, Michael}, title = {Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor}, series = {Cell and Tissue Research}, volume = {382}, journal = {Cell and Tissue Research}, doi = {10.1007/s00441-020-03224-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235055}, pages = {5-14}, year = {2020}, abstract = {Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.}, language = {en} }