The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predo... more The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.
N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are abundant mRNA modifications tha... more N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed mA/m, in the stress response in the adult brain in vivo is currently unknown. Here, we provide a detailed analysis of the stress epitranscriptome using mA/m-seq, global and gene-specific mA/m measurements. We show that stress exposure and glucocorticoids region and time specifically alter mA/m and its regulatory network. We demonstrate that deletion of the methyltransferase Mettl3 or the demethylase Fto in adult neurons alters the mA/m epitranscriptome, increases fear memory, and changes the transcriptome response to fear and synaptic plasticity. Moreover, we report that regulation of mA/m is impaired in major depressive disorder patients following glucocorticoid stimulation. Our findings indicate that brain mA/m represents a novel layer of complexity in gene expression regulation after stress and that dysreg...
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Caan... more Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Caand Mnto map the brain's activity in vivo. However, to what extent different Cachannels contribute to the enhanced signal that MEMRI provides and how Mndynamics influence Mnbrain accumulation after systemic administration of MnClare not yet fully understood. Here, we demonstrate that mice lacking the L-type Cachannel 1.2 (Ca1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnClinjections, as compared to control mice. In contrast, genetic deletion of L-type Cachannel 1.3 (Ca1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Ca1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mnin projection terminals, which was confirmed by local MnCladministration to defined brain areas. Taken together, we provide unequivocal evidence that Ca1.2 represents an important channel for neuronal M...
The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network ... more The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations co...
Stress and an altered stress response have been associated with many multifactorial diseases, suc... more Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid ...
An imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic system... more An imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disturbances.
The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predo... more The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.
N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are abundant mRNA modifications tha... more N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed mA/m, in the stress response in the adult brain in vivo is currently unknown. Here, we provide a detailed analysis of the stress epitranscriptome using mA/m-seq, global and gene-specific mA/m measurements. We show that stress exposure and glucocorticoids region and time specifically alter mA/m and its regulatory network. We demonstrate that deletion of the methyltransferase Mettl3 or the demethylase Fto in adult neurons alters the mA/m epitranscriptome, increases fear memory, and changes the transcriptome response to fear and synaptic plasticity. Moreover, we report that regulation of mA/m is impaired in major depressive disorder patients following glucocorticoid stimulation. Our findings indicate that brain mA/m represents a novel layer of complexity in gene expression regulation after stress and that dysreg...
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Caan... more Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Caand Mnto map the brain's activity in vivo. However, to what extent different Cachannels contribute to the enhanced signal that MEMRI provides and how Mndynamics influence Mnbrain accumulation after systemic administration of MnClare not yet fully understood. Here, we demonstrate that mice lacking the L-type Cachannel 1.2 (Ca1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnClinjections, as compared to control mice. In contrast, genetic deletion of L-type Cachannel 1.3 (Ca1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Ca1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mnin projection terminals, which was confirmed by local MnCladministration to defined brain areas. Taken together, we provide unequivocal evidence that Ca1.2 represents an important channel for neuronal M...
The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network ... more The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations co...
Stress and an altered stress response have been associated with many multifactorial diseases, suc... more Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated and phenotyped in a large-scale manner, it seems advisable also to test these mutants for alterations in their stress responses. Here we present the determinants of a robust and reliable non-invasive test for stress-responsivity in mice. Stress is applied through restraining the mice in tubes and recording behavior in the Open Field 20 min after cessation of the stress. Two hours, but not 15 or 50 min of restraint lead to a robust and reproducible increase in distance traveled and number of rearings during the first 5 min in the Open Field in C57BL/6 mice. This behavioral response is blocked by the corticosterone synthesis inhibitor metyrapone, but not by RU486 treatment, indicating that it depends on corticosteroid secretion, but is not mediated via the glucocorticoid ...
An imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic system... more An imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disturbances.
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Papers by Jan Deussing