TY  - JOUR
AU  - Niethard, N.
C1  - 75174
C2  - 57841
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Phase-amplitude coupling in sleep EEG-stable trait or shaped by experience? (Commentary on Cross et al., 2025).
JO  - Eur. J. Neurosci.
VL  - 62
IS  - 2
PB  - Wiley
PY  - 2025
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Among the various forms of exploration, rearing-where rodents stand on their hind legs-reflects the animal's processing of spatial information and response to environmental novelty. Here, we investigated the developmental trajectory of rearing in response to spatial novelty in a standard object-place recognition (OPR) task, with the OPR retrieval phase allowing for a direct comparison of measures of rearing, object exploration, and locomotion as indicators of spatial novelty and memory. Groups of male rats were tested on postnatal day (PD) 25, PD31, PD38, PD48, and at adulthood (PD84). The OPR task comprised a 5-min encoding phase with the rat exposed to an arena with two identical objects and, 3 h later, a 5-min retrieval phase in the same arena with one object being displaced to another arena zone. Rearing increased in response to spatial novelty (i.e., the displaced object) at retrieval relative to encoding, with this increase occurring first on PD31, and thus later than preferential object exploration-based responses emerging already on PD25. Importantly, zone-specific analyses during retrieval revealed an increase in rearing events in the (now empty) zone where the displaced object is used to be at encoding. This increase was only observed in adult rats (PD84) and likely indicates the presence of specific object-place associations in memory. These findings evidence rearing as behavior covering aspects of spatial novelty complementary to those of object exploration, thereby enabling a more comprehensive characterization of the emergence of spatial episodic memory during early life.
AU  - Shan, X.*
AU  - Sawangjit, A.*
AU  - Born, J.
AU  - Inostroza, M.*
C1  - 74989
C2  - 57779
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Rearing behavior as indicator of spatial novelty and memory in developing rats.
JO  - Eur. J. Neurosci.
VL  - 61
IS  - 12
PB  - Wiley
PY  - 2025
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in patients with MDS. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 patients with RTT, and performed multi-omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT and KIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.
AU  - Pascual-Alonso, A.*
AU  - Xiol, C.*
AU  - Smirnov, D.
AU  - Kopajtich, R.
AU  - Prokisch, H.
AU  - Armstrong, J.*
C1  - 70679
C2  - 55811
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Multi-omics in MECP2 duplication syndrome patients and carriers.
JO  - Eur. J. Neurosci.
PB  - Wiley
PY  - 2024
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Major depressive disorder (MDD) is one of the most severe global health problems with millions of people affected, however, the mechanisms underlying this disorder is still poorly understood. Genome-wide association studies have highlighted a link between the neutral amino acid transporter SLC6A15 and MDD. Additionally, a number of preclinical studies support the function of this transporter in modulating levels of brain neurotransmitters, stress system regulation and behavioural phenotypes related to MDD. However, the molecular and functional mechanisms involved in this interaction are still unresolved. Therefore, to investigate the effects of the SLC6A15 transporter, we used hippocampal tissue fromSlc6a15-KO and wild-type mice, together with several in-vitro assays in primary hippocampal neurons. Utilizing a proteomics approach we identified differentially regulated proteins that formed a regulatory network and pathway analysis indicated significantly affected cellular domains, including metabolic, mitochondrial and structural functions. Furthermore, we observed reduced release probability at glutamatergic synapses, increased mitochondrial function, higher GSH/GSSG redox ratio and an improved neurite outgrowth in primary neurons lacking SLC6A15. In summary, we hypothesize that by controlling the intracellular concentrations of neutral amino acids, SLC6A15 affects mitochondrial activity, which could lead to alterations in neuronal structure and activity. These data provide further indication that a pharmacological or genetic reduction of SLC6A15 activity may indeed be a promising approach for antidepressant therapy.
AU  - Schraut, K.G.*
AU  - Kalnytska, O.*
AU  - Lamp, D.
AU  - Jastroch, M.
AU  - Eder, M.*
AU  - Hausch, F.*
AU  - Gassen, N.C.*
AU  - Moore, S.*
AU  - Nagaraj, N.*
AU  - Lopez, J.P.*
AU  - Chen, A.*
AU  - Schmidt, M.V.*
C1  - 60328
C2  - 49255
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 390-401
TI  - Loss of the psychiatric risk factor SLC6A15 is associated with increased metabolic functions in primary hippocampal neurons.
JO  - Eur. J. Neurosci.
VL  - 53
IS  - 2
PB  - Wiley
PY  - 2021
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Intrafusal fibers of muscle spindles are innervated in the central region by afferent sensory axons and at both polar regions by efferent γ-motoneurons. We previously demonstrated that both neuron-muscle contact sites contain cholinergic synapse-like specialisation, including aggregates of the nicotinic acetylcholine receptor (AChR). In this study we tested the hypothesis that agrin and its receptor complex (consisting of LRP4 and the tyrosine kinase MuSK) are involved in the aggregation of AChRs in muscle spindles, similar to their role at the neuromuscular junction. We show that agrin, MuSK and LRP4 are concentrated at the contact site between the intrafusal fibers and the sensory- and γ-motoneuron, respectively, and that they are expressed in the cell bodies of proprioceptive neurons in dorsal root ganglia. Moreover, agrin and LRP4, but not MuSK, are expressed in γ-motoneuron cell bodies in the ventral horn of the spinal cord. In agrin- and in MuSK-deficient mice, AChR aggregates are absent from the polar regions. In contrast, the subcellular concentration of AChRs in the central region where the sensory neuron contacts the intrafusal muscle fiber is apparently unaffected. Skeletal muscle-specific expression of miniagrin in agrin(-/-) mice in vivo is sufficient to restore the formation of γ-motoneuron endplates. These results show that agrin and MuSK are major determinants during the formation of γ-motoneuron endplates but appear dispensable for the aggregation of AChRs at the central region. Our results therefore suggest different molecular mechanisms for AChR clustering within two domains of intrafusal fibers.
AU  - Zhang, Y.
AU  - Lin, S.*
AU  - Karakatsani, A.*
AU  - Rüegg, M.A.*
AU  - Kröger, S.*
C1  - 34374
C2  - 35261
CY  - Hoboken
SP  - 69-78
TI  - Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles.
JO  - Eur. J. Neurosci.
VL  - 41
IS  - 1
PB  - Wiley-blackwell
PY  - 2015
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - It has been shown previously (Sotnikov et al., 2011) that mice selectively inbred for high anxiety-related behavior (HAB) vs. low anxiety-related behavior in the elevated plus maze differentially respond to trimethylthiazoline (TMT), a synthetic fox fecal odor. However, less is known about whether environmental factors can rescue these extreme phenotypes. Here, we found that an enriched environment (EE) provided during early adolescence induced anxiolytic effects in HAB (HAB-EE) mice, rescuing their strong avoidance behavior induced by TMT. In a series of experiments, the contribution of maternal, juvenile and adolescent behavior to the anxiolytic effects elicited by EE was investigated. At the molecular level, using c-fos expression mapping, we found that the activity of the medial and basolateral amygdala was significantly reduced in HAB-EE mice after TMT exposure. We further analysed the expression of Crhr1, as its amount in the amygdala has been reported to be important for the regulation of anxiety-related behavior after EE. Indeed, in situ hybridisation indicated significantly decreased Crhr1 expression in the basolateral and central amygdala of HAB-EE mice. To further test the involvement of Crhr1 in TMT-induced avoidance, we exposed conditional glutamatergic-specific Crhr1-knockout mice to the odor. The behavioral response of Crhr1-knockout mice mimicked that of HAB-EE mice, and c-fos expression in the amygdala after TMT exposure was significantly lower compared with controls, thereby further supporting a critical involvement of Crhr1 in environmentally-induced anxiolysis. Altogether, our results indicate that EE can rescue strong avoidance of TMT by HAB mice with Crhr1 expression in the amygdala being critically involved.
AU  - Sotnikov, S.V.*
AU  - Chekmareva, N.Y.*
AU  - Schmid, B.*
AU  - Harbich, D.*
AU  - Malik, V.*
AU  - Bauer, S.*
AU  - Kuehne, C.*
AU  - Markt, P.O.*
AU  - Deussing, J.M.
AU  - Schmidt, M.V.*
AU  - Landgraf, R.*
C1  - 32528
C2  - 35120
CY  - Hoboken
SP  - 2691-2700
TI  - Enriched environment impacts trimethylthiazoline-induced anxiety-related behavior and immediate early gene expression: Critical role of Crhr1.
JO  - Eur. J. Neurosci.
VL  - 40
IS  - 4
PB  - Wiley-blackwell
PY  - 2014
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Early-life stress may lead to persistent changes in central corticotropin-releasing hormone (CRH) and the CRH receptor 1 (CRHR1) system that modulates anxiety-related behavior. However, it remains unknown whether CRH–CRHR1 signaling is involved in earlylife stress-induced anxiety-related behavior in adult animals. In the present study, we used conditional forebrain CRHR1 knockout (CRHR1-CKO) mice and examined the potential role of forebrain CRHR1 in the anxiogenic effects of early-life stress. As adults, wildtype mice that received unstable maternal care during the first postnatal week showed reduced body weight gain and increased anxiety levels in the open field test, which were prevented in stressed CRHR1-CKO mice. In the light–dark box test, control CRHR1- CKO mice were less anxious, but early-life stress increased anxiety levels in both wild-type and CRHR1-CKO mice. In the elevated plus maze test, early-life stress had only subtle effects on anxiety-related behavior. Moreover, early-life stress did not alter the basal home cage activity and gene expression levels of key hypothalamic-pituitary-adrenal axis regulators in adult wild-type and CRHR1- CKO mice, but enhanced neuroendocrine reactivity to acute immobilization stress in CRHR1-CKO mice. Our findings highlight the importance of forebrain CRHR1 in modulating some of the anxiogenic effects of early-life stress, and suggest that other neural circuits are also involved in the programming effects of early-life stress on anxiety-related behavior.
AU  - Wang, X.D.*
AU  - Labermaier, C.*
AU  - Holsboer, F.*
AU  - Wurst, W.
AU  - Deussing, J.M.*
AU  - Müller, M.B.*
AU  - Schmidt, M.V.*
C1  - 7474
C2  - 29734
SP  - 2360-2367
TI  - Early-life stress-induced anxiety-related behavior in adult mice partially requires forebrain corticotropin-releasing hormone receptor 1.
JO  - Eur. J. Neurosci.
VL  - 36
IS  - 3
PB  - Wiley-Blackwell 
PY  - 2012
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - By combining behavioural analyses with intrinsic signal optical imaging, we analysed visual performance and visual cortical activity in the albino mouse strain BALB/c, which is increasingly being used as an animal model of neuropsychological disorders. Visual acuity, as measured by a virtual-reality optomotor system, was 0.12 cycles per degree (cyc/deg) in BALB/c mice and 0.39 cyc/deg in pigmented C57BL/6 mice. Surprisingly, BALB/c mice showed reflexive head movements against the direction of the rotating stimulus. Contrast sensitivity was significantly lower in BALB/c mice (45% contrast at 0.064 cyc/deg) than in C57BL/6 mice (6% contrast). In the visual water task, visual acuity was 0.3 cyc/deg in BALB/c mice and 0.59 cyc/deg in C57BL/6 mice. Thus, the visual performance of BALB/c mice was significantly impaired in both behavioural tests - visual acuity was ∼ 0.3 cyc/deg lower than in C57BL/6 mice, and contrast sensitivity was reduced by a factor of ∼ 8. In BALB/c mice, visual cortical maps induced by stimulation of the contralateral eye were normal in both activation strength and retinotopic map quality. In contrast, maps induced by ipsilateral eye stimulation differed significantly between the strains - activity in a region representing 15° to 19° elevation in the visual field was significantly weaker in BALB/c mice than in C57BL/6 mice. Taken together, our observations show that BALB/c mice, like the albino animals of other species, have a significantly lower visual performance than C57BL/6 mice and a modified cortical representation of the ipsilateral eye that may impair stereopsis. Thus, our results caution against disregarding vision as a confounding factor in behavioural tests of neuropsychological disorders.
AU  - Yeritsyan, N.*
AU  - Lehmann, K.*
AU  - Puk, O.
AU  - Graw, J.
AU  - Löwel, S.*
C1  - 8396
C2  - 30077
SP  - 2801-2811
TI  - Visual capabilities and cortical maps in BALB/c mice.
JO  - Eur. J. Neurosci.
VL  - 36
IS  - 6
PB  - Wiley-Blackwell
PY  - 2012
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - The generation of new neurons in the adult brain is modulated by complex stimuli and a broad range of extrinsic signals. It remains a mystery how stem cells and their progeny integrate this wealth of regulatory input to generate a precise number of neurons that matches the physiological needs of the olfactory and hippocampal network. cAMP response element binding protein (CREB)-dependent signalling is controlling essential developmental steps in adult neurogenesis, i.e. survival, maturation and integration of new neurons. Here, we summarize the current knowledge on the function of CREB in adult neurogenesis and discuss the potential of CREB to integrate complex stimuli and to translate these into precise developmental processes in adult neurogenesis. The complex modulation of CREB-signalling may allow the adult neurogenic system to respond to stimuli in a fine-tuned rather than in an on-off fashion.
AU  - Merz, K.
AU  - Herold, S.
AU  - Lie, D.C.
C1  - 5047
C2  - 28812
SP  - 1078-1086
TI  - CREB in adult neurogenesis - master and partner in the development of adult-born neurons?
JO  - Eur. J. Neurosci.
VL  - 33
IS  - 6
PB  - Blackwell Publishing Ltd.
PY  - 2011
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Key questions in regard to neuronal repair strategies are which cells are best suited to regenerate specific neuronal subtypes and how much of a neuronal circuit needs to persist in order to allow its functional repair. Here we discuss recent findings in the field of adult neurogenesis, which shed new light on these questions. Neural stem cells in the adult brain generate very distinct types of neurons depending on their regional and temporal specification. Moreover, distinct brain regions differ in the mode of neuron addition in adult neurogenesis, suggesting that different brain circuits may be able to cope differently with the incorporation of new neurons. These new insights are then considered in regard to the choice of cells with the appropriate region-specific identity for repair strategies.
AU  - Weinandy, F.
AU  - Ninkovic, J.
AU  - Götz, M.
C1  - 4834
C2  - 28546
SP  - 1045-1054
TI  - Restrictions in time and space - new insights into generation of specific neuronal subtypes in the adult mammalian brain.
JO  - Eur. J. Neurosci.
VL  - 33
IS  - 6
PB  - Wiley-Blackwell
PY  - 2011
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - In early development, an excess of neurons is generated, of which later about half will be lost by cell death due to a limited supply of trophic support by their respective target areas. However, some of the neurons die when their axons have not yet reached their target, thus suggesting that additional causes of developmental cell death exist. Semaphorin 3A (Sema3A), in addition to its function as a guidance cue and mediator of timing and fasciculation of motor and sensory axon outgrowth, can also induce death of sensory neurons in vitro. However, it is unknown whether Neuropilin-1 (Npn-1), its binding receptor in axon guidance, also mediates the death-inducing activity. We show here that abolished Sema3A-Npn-1 signaling does not influence the cell death patterns of motor or sensory neurons in mouse during the developmental wave of programmed cell death. The number of motor and sensory neurons was unchanged at embryonic day 15.5 when this wave is concluded. Interestingly, the defasciculation of early motor and sensory projections that is observed in the absence of Sema3A or Npn-1 persists to postnatal stages. Thus, Sema3A-Npn-1 signaling plays an important role in the guidance and fasciculation of motor and sensory axons but does not contribute to the developmental elimination of these neurons.
AU  - Haupt, C.
AU  - Kloos, K.
AU  - Faus-Kessler, T.
AU  - Huber, A.B.
C1  - 2370
C2  - 27372
SP  - 1164-1172
TI  - Semaphorin 3A-Neuropilin-1 signaling regulates peripheral axon fasciculation and pathfinding but not developmental cell death patterns.
JO  - Eur. J. Neurosci.
VL  - 31
IS  - 7
PB  - Wiley-Blackwell Publishing
PY  - 2010
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor (GEF) that is essential for the synaptic clustering of gephyrin and GABAA receptors in selected regions of the mammalian central nervous system. It has been previously proposed that Cb regulates gephyrin clustering by activating Cdc42, and thus acts as a signal transducer in a membrane activation process which labels postsynaptic membrane domains for inhibitory synapse formation. Here, we dissected the functional roles of the Dbl-homology (DH) and pleckstrin homology (PH) domains of the constitutively active splice variant Cb II by substituting conserved amino acid residues that are required for GEF activity towards Cdc42 and phosphoinositide binding, respectively. A Cb II mutant lacking any detectable GEF activity towards Cdc42 was still fully active in inducing gephyrin scaffold formation, both in transfected NIH-3T3 cells and in cultured hippocampal neurons. Furthermore, mice with a forebrain-specific inactivation of the Cdc42 gene displayed normal densities of gephyrin and GABA(A) receptor clusters in the hippocampus. In contrast, substitution of Cb II PH-domain residues essential for phosphoinositide binding abolished gephyrin recruitment to synaptic sites. Our results provide evidence that the formation of gephyrin scaffolds at inhibitory synapses requires an intact Cb II PH-domain but is Cdc42-independent.
AU  - Reddy-Alla, S.*
AU  - Schmitt, B.*
AU  - Birkenfeld, J.*
AU  - Eulenburg, V.*
AU  - Dutertre, S.*
AU  - Böhringer, C.R.
AU  - Götz, M.
AU  - Betz, H.*
AU  - Papadopoulos, T.*
C1  - 1568
C2  - 27198
SP  - 1173-1184
TI  - PH-domain-driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering.
JO  - Eur. J. Neurosci.
VL  - 31
IS  - 7
PB  - Blackwell Publishing
PY  - 2010
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - In the mammalian brain, neural stem and progenitor cells in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus generate new neurons throughout adulthood. The generation of new functional neurons is a complex process that is tightly controlled by extrinsic signals and that is characterized by stage-specific gene expression programs and cell biological processes. The transcription factors regulating such stage-specific developmental steps in adult neurogenesis are largely unknown. Here we report that Sox11, a member of the group C Sox transcription factor family, is prominently expressed in the neurogenic areas of the adult brain. Further analysis revealed that Sox11 expression is strictly confined to doublecortin-expressing neuronally committed precursors and immature neurons but that Sox11 is not expressed in non-committeAdult Stem Cells/cytology; Adult Stem Cells/physiology*; Aging/physiology; Animals; Cell Differentiation/physiology; Cell Line; Cells, Cultured; Gene Expression Regulation, Developmental*; Humans; Male; Mice; Mice, Inbred C57BL; Neurogenesis/physiology*; Neurons/cytology; Neurons/physiology*; SOXC Transcription Factors/biosynthesis*; SOXC Transcription Factors/genetics; SOXC Transcription Factors/physiologyd Sox2-expressing precursor cells and mature neurons of the adult neurogenic lineage. Finally, overexpression of Sox11 promotes the generation of doublecortin-positive immature neurons from adult neural stem cells in vitro. These data indicate that Sox11 is involved in the transcriptional regulation of specific gene expression programs in adult neurogenesis at the stage of the immature neuron.
AU  - Haslinger, A.
AU  - Schwarz, T.J.
AU  - Covic, M.
AU  - Lie, D.C.
C1  - 1229
C2  - 26783
SP  - 2103-2114
TI  - Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesis.
JO  - Eur. J. Neurosci.
VL  - 29
IS  - 11
PB  - Wiley-Blackwell
PY  - 2009
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - In-vitro expanded neural stem cells (NSCs) of the adult subependymal zone (SEZ) may serve as a source for replacing degenerating neurones in disease and trauma. Crucial for the viability of this approach is the ability to selectively generate specific types of neurones from these cells. Here we show that NSCs derived from the adult mouse SEZ and expanded in vitro as neurosphere cells lose their in-vivo specification and generate a mixture of progeny comprising both GABAergic and also, surprisingly, glutamatergic neurones. When forced to express the pro-neural transcription factor neurogenin 2, virtually all progeny of in-vitro expanded adult NSCs acquire a glutamatergic identity, whereas only GABAergic neurones are generated upon expression of the transcription factor Mash1. Respecification of expanded NSCs from the adult SEZ by neurogenin 2 was accompanied by upregulation of the T-box transcription factor Tbr1, suggesting that their progeny had acquired a dorsal telencephalic identity. Thus, in-vitro expanded adult NSCs have the competence to become directed towards distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided.
AU  - Berninger, B.
AU  - Guillemot, F.*
AU  - Götz, M.
C1  - 757
C2  - 24682
SP  - 2581-2590
TI  - Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells.
JO  - Eur. J. Neurosci.
VL  - 25
IS  - 9
PB  - Blackwell
PY  - 2007
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - In the adult, corticotropin-releasing hormone (CRH) is the key mediator for the behavioural and neuroendocrine response to stress. It has also been hypothesized that, during postnatal development of the stress system, CRH controls the activity of the HPA axis and mediates the effects of early disturbances, e.g. 24 h of maternal deprivation. In the current study we investigated the function of specific brain corticotropin-releasing hormone receptor type 1 (CRHR1) subpopulations in the control of the HPA axis during postnatal development under basal conditions as well as after 24 h of maternal deprivation. We used two conditional CRHR1-deficient mouse lines which lack this receptor, either specifically in forebrain and limbic structures (Cam-CRHR1) or in all neurons (Nes-CRHR1). Basal circulating corticosterone was increased in Nes-CRHR1 mice compared to controls. Corticosterone response to maternal deprivation was significantly increased in both CRHR1-deficient lines. In the paraventricular nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin expression levels. In contrast, gene expression in Nes-CRHR1 pups was strikingly similar to that in maternally deprived control pups. Furthermore, maternal deprivation resulted in an enhanced response of Cam-CRHR1 pups in the brain, while expression levels in Nes-CRHR1 mouse pups were mostly unchanged. Our results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the suppression of basal corticosterone secretion in the neonate, while limbic and/or forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by maternal deprivation.
AU  - Schmidt, M.V.*
AU  - Deussing, J.M.*
AU  - Oitzl, M.S.*
AU  - Ohl, F.*
AU  - Levine, S.*
AU  - Wurst, W.
AU  - Holsboer, F.*
AU  - Müller, M.B.*
AU  - de Kloet, E.R.*
C1  - 5110
C2  - 24144
SP  - 2291-2298
TI  - Differential disinhibition of the neonatal hypothalamic-pituitary-adrenal axis in brain-specific CRH receptor 1-knockout mice.
JO  - Eur. J. Neurosci.
VL  - 24
IS  - 8
PY  - 2006
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Progression of progenitor cells towards neuronal differentiation is tightly linked with cell cycle control and the switch from proliferative to neuron-generating divisions. We have previously shown that the neuronal protein BM88 drives neuroblastoma cells towards exit from the cell cycle and differentiation into a neuronal phenotype in vitro. Here, we explored the role of BM88 during neuronal birth, cell cycle exit and the initiation of differentiation in vivo. By double- and triple-labelling with the S-phase marker BrdU or the late G2 and M-phase marker cyclin B1, antibodies to BM88 and markers of the neuronal or glial cell lineages, we demonstrate that in the rodent forebrain, BM88 is expressed in multipotential progenitor cells before terminal mitosis and in their neuronal progeny during the neurogenic interval, as well as in the adult. Further, we defined at E16 a cohort of proliferative progenitors that exit S phase in synchrony, and by following their fate for 24 h we show that BM88 is associated with the dynamics of neuron-generating divisions. Expression of BM88 was also evident in cycling cortical radial glial cells, which constitute the main neurogenic population in the cerebral cortex. In agreement, BM88 expression was markedly reduced and restricted to a smaller percentage of cells in the cerebral cortex of the Small eye mutant mice, which lack functional Pax6 and exhibit severe neurogenesis defects. Our data show an interesting correlation between BM88 expression and the progression of progenitor cells towards neuronal differentiation during the neurogenic interval.
AU  - Koutmani, Y.*
AU  - Hurel, C.*
AU  - Patsavoudi, E.*
AU  - Hack, M.*
AU  - Götz, M.
AU  - Thomaidou, D.*
AU  - Matsas, R.*
C1  - 2125
C2  - 22269
SP  - 2509-2523
TI  - BM88 is an early marker of proliferating precursor cells that will differentiate into the neuronal lineage.
JO  - Eur. J. Neurosci.
VL  - 20
IS  - 10
PY  - 2004
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Cyclic GMP is a second messenger for nitric oxide (NO) that acts as a mediator for many different physiological functions. The cGMP-dependent protein kinases (cGKs) mediate cellular signalling induced by NO and cGMP. Here, we explored the localization of cGMP-dependent protein kinase type II (cGKII) in the mouse brain. In situ hybridization revealed high levels of cGKII mRNA in cerebral cortex, thalamic nuclei, hypothalamic nuclei, and in several basal forebrain regions including medial septum, striatum and amygdala. The close link to NO and the distribution pattern of cGKII suggested that this enzyme might be involved in emotional reactions and responses to drugs of abuse. Therefore, cGKII knockout animals (cGKII–/–) were compared with littermate controls in behavioural tests (i) for emotion-linked and (ii) for acute and chronic ethanol responses. Deletion of cGKII did not influence aggressive behaviour but led to enhanced anxiety-like behaviour. In terms of acute responses to ethanol, cGKII–/– mice were hyposensitive to hypnotic doses of ethanol as measured by the loss of righting reflex, without an alteration in their blood alcohol elimination. In a two-bottle free choice test, cGKII–/– mice showed elevated alcohol consumption. No taste differences to sweet solutions were observed compared to control animals. In summary, our data show that cGKII activity modulates anxiety-like behaviour and neurobehavioural effects of alcohol.
AU  - Werner, C.*
AU  - Raivich, G.*
AU  - Cowen, M.*
AU  - Strekalova, T.*
AU  - Sillaber, I.*
AU  - Buters, J.T.M.
AU  - Hofmann, F.
C1  - 5336
C2  - 22534
SP  - 3498-3506
TI  - Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol.
JO  - Eur. J. Neurosci.
VL  - 20
IS  - 12
PY  - 2004
SN  - 0953-816X
ER  - 

TY  - JOUR
AB  - Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels codetermine the integrative behaviour of neurons and shape their response to synaptic stimulation. We used immunohistochemistry and patch-clamp recording to study the composition and distribution of HCN channels in the rat retina. All four HCN channel isoforms (HCN1–4) are expressed differentially in the retina. In particular, different classes of bipolar cells have a different inventory of HCN channels. We found no evidence for the formation of heterooligomeric HCN channels. HCN channels are densely clustered at synaptic terminals of bipolar cells and photoreceptors. This suggests that HCN channels are involved in the control of transmitter release.
AU  - Müller, F.*
AU  - Scholten, A.*
AU  - Ivanova, E.*
AU  - Haverkamp, S.*
AU  - Kremmer, E.
AU  - Kaupp, U.B.*
C1  - 10187
C2  - 21426
SP  - 2084-2096
TI  - HCN channels are expressed differentially in retinal bipolar cells and concentrated at synaptic terminals.
JO  - Eur. J. Neurosci.
VL  - 17
IS  - 10
PY  - 2003
SN  - 0953-816X
ER  -