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Publications (48)
Measuring autonomic parameters like heart rate in behaving mice is not only a standard procedure in cardiovascular research but is applied in many other interdisciplinary research fields. With an electrocardiogram (ECG), the heart rate can be measured by deriving the electrical potential between subcutaneously implanted wires across the chest. This...
Background
Migraine is a disabling neurological disorder, characterized by recurrent headaches. During migraine attacks, individuals often experience sensory symptoms such as cutaneous allodynia which indicates the presence of central sensitization. This sensitization is prevented by oral administration of propranolol, a common first-line medicatio...
In Parkinson's disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a "circuitopathy". We therefore developed a ce...
Despite fine tuning voluntary movement as the most prominently studied function of the cerebellum, early human studies suggested cerebellar involvement emotion regulation. Since, the cerebellum has been associated with various mood and anxiety-related conditions. Research in animals provided evidence for cerebellar contributions to fear memory form...
Bioimages frequently exhibit low signal-to-noise ratios due to experimental conditions, specimen characteristics, and imaging trade-offs. Reliable segmentation of such ambiguous images is difficult and laborious. Here we introduce deepflash2, a deep learning-enabled segmentation tool for bioimage analysis. The tool addresses typical challenges that...
Fear and anxiety are brain states that evolved to mediate defensive responses to threat. While it is clear that the defense reaction includes multiple interacting behavioural, autonomic and endocrine adjustments, their integrative nature is poorly understood. In particular, threat has been associated with various cardiac changes, yet a clear consen...
Sylite, eine kurze, dimerisierte Fluoreszenzsonde auf Peptidbasis, bindet Gephyrin, ein charakteristisches Protein der inhibitorischen Synapse. Wie Christian G. Specht, Hans M. Maric et al. in ihrem Forschungsartikel (DOI: 10.1002/ange.202202078) berichten, macht Sylite inhibitorische Synapsen sowohl in Neuronenkulturen als auch in Hirngewebe sicht...
Adequate defensive responding is crucial for mental health but scientifically not well understood. Specifically, it seems difficult to dissociate defense and approach states based on autonomic response patterns. We thus explored the robustness and threat-specificity of recently described oculomotor dynamics upon threat in anticipation of either thr...
Visualization of inhibitory synapses requires protocols tailored to different sample types and imaging techniques, and usually relies on genetic manipulation or the use of antibodies that underperform in tissue immunofluorescence. Starting from an endogenous ligand of gephyrin, a universal marker of the inhibitory synapse, we developed a short pept...
Visualization of inhibitory synapses requires protocol tailoring for different sample types and imaging techniques, and usually relies on genetic manipulation or the use of antibodies that underperform in tissue immunofluorescence. Starting from an endogenous ligand of gephyrin, a universal marker of the inhibitory synapse, we developed a short pep...
Accelerating technological progress in experimental neuroscience is increasing the scale as well as specificity of both observational and perturbational approaches to study circuit physiology. While these techniques have also been used to study disease mechanisms, a wider adoption of these approaches in the field of experimental neurology would gre...
Gait impairments in Parkinson's disease remain a scientific and therapeutic challenge. The advent of new deep brain stimulation (DBS) devices capable of recording brain activity from chronically implanted electrodes has fostered new studies of gait in freely moving patients. The hope is to identify gait-related neural biomarkers and improve therapy...
We present deepflash2, a deep learning solution that facilitates the objective and reliable segmentation of ambiguous bioimages through multi-expert annotations and integrated quality assurance. Thereby, deepflash2 addresses typical challenges that arise during training, evaluation, and application of deep learning models in bioimaging. The tool is...
Brain-wide neural circuits enable bi- and quadrupeds to express adaptive locomotor behaviors in a context- and state-dependent manner, e.g., in response to threats or rewards. These behaviors include dynamic transitions between initiation, maintenance and termination of locomotion. Advances within the last decade have revealed an intricate coordina...
Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation of extinction memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA is...
We introduce Sylites - small and versatile fluorogenic affinity probes for high-contrast visualization of inhibitory synapses. Having stoichiometric labeling and exceptional selectivity for neuronal gephyrin, a hallmark protein of the inhibitory post-synapse, Sylites enable superior synapse staining compared with antibodies. Combined with super-res...
TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30–40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify centr...
A GWAS study recently demonstrated single nucleotide polymorphisms (SNPs) in the human GLRB gene of individuals with a prevalence for agoraphobia. GLRB encodes the glycine receptor (GlyRs) β subunit. The identified SNPs are localized within the gene flanking regions (3′ and 5′ UTRs) and intronic regions. It was suggested that these nucleotide polym...
Motor learning depends on synaptic plasticity between corticostriatal projections and striatal medium spiny neurons. Retrograde tracing from the dorsolateral striatum reveals that both layer II/III and V neurons in the motor cortex express BDNF as a potential regulator of plasticity in corticostriatal projections in male and female mice. The number...
Rapid-onset dystonia-parkinsonism (RDP) is a rare form of hereditary dystonia caused by loss-of-function mutations of the Na+/K+-ATPase α3 isoform (ATP1α3). An acute onset of generalized dystonia and parkinsonism after exposure to stress and an incomplete disease penetrance is described in RDP, thereby suggesting a gene-environmental interaction in...
Memory of cues associated with threat is critical for survival and a leading model for elucidating how sensory information is linked to adaptive behavior by learning. Although the brain-wide circuits mediating auditory threat memory have been intensely investigated, it remains unclear whether the auditory cortex is critically involved. Here we use...
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The central nucleus of the amygdala (CEA) is a striatum-like structure orchestrating a diverse set of adaptive behaviors, including defensive and appetitive responses. Studies using anatomical, electrophysiological, imaging and optogenetic approaches r...
When faced with threat, the survival of an organism is contingent upon the selection of appropriate active or passive behavioural responses. Freezing is an evolutionarily conserved passive fear response that has been used extensively to study the neuronal mechanisms of fear and fear conditioning in rodents. However, rodents also exhibit active resp...
Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey cir...
Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex...
Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral...
Corticotropin-releasing factor (CRF) plays an essential role in coordinating the autonomic, endocrine and behavioral responses to stressors. In this study, we investigated the role of CRF within the medial prefrontal cortex (mPFC) in modulating unconditioned defensive behaviors, by examining the effects of microinfusing cortagine a selective type-1...
In optogenetics, neurons are genetically modified to become sensitive to light and thus, they can be stimulated or inhibited by light of certain wavelengths. In this work, we describe the fabrication of a polymer-based shaft electrode as a tool for optogenetics. This device can conduct light as well as fluids to a target brain region and record ele...
Oxytocin produces anxiolytic effects via the central nucleus of the amygdala but how the peptide reaches its receptors in this region has been unclear. In this issue of Neuron, Knobloch et al. (2012) demonstrate that evoked oxytocin release from axon terminals within the central amygdala results in attenuation of fear.
Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local netwo...
In this work, we describe the fabrication of a polymer-based shaft electrode which can conduct light as well as fluids to a target brain region and record electrical neural signals from the same tissue volume simultaneously. This multifunctional neural probe is intended to facilitate optogenetic in vivo experiments.
CRF receptor subtype 1 (CRF1), abundantly expressed in the central nervous system, has been implicated in defensive behavior in rodents. Pharmacological activation of CRF1 by peptidic agonists results in enhancement of anxiety-like behavior. However, receptor specificity of commonly used agonists was confounded by significant affinity to other rece...
Corticotropin-releasing factor (CRF), a 41 amino acid peptide, was discovered as a key signal in mediating neuroendocrine, autonomic, and behavioral responses to stress. It was revealed later that there exist additional CRF-like peptides, termed urocortins. The CRF receptor subtype 1 (CRF1 receptor) is predominant in the brain whereas subtype 2 (CR...
Early-life stress produces an anxiogenic profile in adulthood, presumably by activating the otherwise quiescent hypothalamic-pituitary-adrenal (HPA) axis during the vulnerable 'stress hyporesponsive period'. While the long-term effects of such early-life manipulations have been extensively characterized, little is known of the short-term effects. H...
Corticotropin-releasing factor (CRF) is a neuropeptide and mediating component of neuroendocrine, autonomic, and behavioral processes associated with the stress response. The two receptor subtypes identified in the mammalian brain, CRF receptor subtype 1 (CRF1) and CRF2, are suggested to differentially modulate these processes. Manipulation of thes...
The role of corticotropin-releasing factor in autonomic regulation of heart rate, heart rate variability and behavior responses was investigated in two genetic mouse models: corticotropin-releasing factor receptor 1-deficient mice, and corticotropin-releasing factor-transgenic mice overexpressing corticotropin-releasing factor. Heart rate was recor...
Fear-inducing stimuli were hypothesized to elicit fast heart rate (HR) responses but slow mean arterial blood pressure (MAP) responses and thus were studied in auditory fear conditioning and acoustic startle at high temporal resolution in freely moving mice and rats. Fear-induced instantaneous acceleration of HR reaching maximum physiological value...
Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl-D-asp...
Aversive conditioning to contextual stimulation was performed in mice implanted with ECG transmitters to investigate heart rate (HR) and behavioral responses during contextual retention. The dynamics of HR were analyzed by advanced nonlinear techniques to uncover central neuroautonomic outflow inferred from its sympathetic (SNS) and parasympathetic...
Neuropeptide Y (NPY) is involved in the regulation of emotionality including fear and anxiety, which modulate autonomic control of cardiovascular function. We therefore investigated the central effects of porcine NPY, selective Y1, Y2 and Y5 receptor agonists and a Y1 receptor antagonist on heart rate (HR) and HR variability in freely moving mice u...
The objective of this study was to isolate and purify prorelaxin or mature relaxin from the tammar wallaby corpus luteum (CL), determine their structure and bioactivity, and test the hypothesis that enzymatic cleavage of prorelaxin occurs in late gestation. Tammar relaxin peptides were extracted from pooled corpora lutea of late pregnant tammars us...
