Thomas Seidenbecher

University of Münster | WWU · Institute of Physiology

Seizure prediction is the grand challenge of epileptology. However, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long-lasting local field potential (LFP) recordings containing several hundred generalized spike and wave discharges (SWDs), acquired at eight locations in the cortico...

The CNS is ensheathed by the meninges and cerebrospinal fluid, and recent findings suggest that these CNS-associated border tissues have complex immunological functions. Unlike myeloid lineage cells, lymphocytes in border compartments have yet to be thoroughly characterized. Based on single-cell transcriptomics, we here identified a highly location...

Through pharmacological manipulation of the serotonergic (5-Hydroxytryptamin, 5-HT) system, combined with behavioral analysis, we tested the hypothesis that fear responses to predictable and unpredictable threat are regulated through stimulation of 5-HT receptors (5-HT-R) in the anterodorsal section of the bed nucleus of the stria terminalis (adBNS...

Key points The major electrophysiological hallmarks of absence seizures are spike and wave discharges (SWDs), consisting of a sharp spike component and a slow wave component. In a widely accepted scheme, these components are functionally coupled and reflect an iterative progression of neuronal excitation during the spike and post‐excitatory silence...

Alterations in cortical cellular organization, network functionality, as well as cognitive and locomotor deficits were recently suggested to be pathological hallmarks in multiple sclerosis and corresponding animal models as they might occur following demyelination. To investigate functional changes following demyelination in a well-defined, topogra...

Multiple sclerosis is characterized by intermingled episodes of de- and remyelination and the occurrence of white- and grey-matter damage. To mimic the randomly distributed pathophysiological brain lesions observed in MS, we assessed the impact of focal white and grey matter demyelination on thalamic function by directing targeted lysolecithin-indu...

The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with u...

Key points: Gap junctional electrical coupling between neurons of the reticular thalamic nucleus (RTN) is critical for hypersynchrony in the thalamo-cortical network. This study investigates the role of electrical coupling in pathological rhythmogenesis in RTN neurons in a rat model of absence epilepsy. Rhythmic activation resulted in a Ca²⁺-depend...

It is well known that adult neurogenesis occurs in two distinct regions, the subgranular zone of the dentate gyrus and the subventricular zone along the walls of the lateral ventricles. Until now, the contribution of these newly born neurons to behavior and cognition is still uncertain. The current study tested the functional impacts of diminished...

Behavioral profiles are strongly shaped by an individual’s whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (‘allostatic load hypothesis’). In contrast, the ‘mismatch hypothesis’ of psychiatric disease suggests that high levels of anxiety-like behavior are the res...

Myelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not wel...

As part of the extended amygdala network, the bed nucleus of the stria terminalis (BNST) was shown to be critically involved in processing sustained fear responses to diffuse and unpredictable threats. However, neuronal activity patterns in relation to sustained components of the fear response remain elusive, so far. We used a fear training paradig...

Sustained fear paradigms in rodents have been developed to monitor states of anxious apprehension and to model situations in patients suffering from long-lasting anxiety disorders. A recent report describes a fear conditioning paradigm, allowing distinction between phasic and sustained states of conditioned fear in non-restrained mice. However, so...

Cumulative stress throughout life time is one of the predominant environmental risk factors for several psychiatric disorders, such as depression or anxiety disorders. So far different hypotheses exist that address the correlation between early and adult chronic stress and the individuals’ vulnerability to psychiatric diseases. The match/mismatch h...

Fear-potentiated acoustic startle paradigms have been used to investigate phasic and sustained components of conditioned fear in rats and humans. The present study describes a novel training protocol to assess phasic and sustained fear in freely behaving C57BL/6J mice, using freezing and/or fear-potentiated startle as measures of fear, thereby, if...

Functional Kv7 channels' existence in thalamocortical relay (TC) neurons and impact of M-type K+-current (IM) on thalamic signal processing have long been debated. Immunocytochemical evidence suggests their presence in this brain region. Therefore we aimed to verify their existence, pharmacological properties and function in regulating activity in...

Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavi...

Data comparability between different laboratories strongly depends on the individually applied analysis method. This factor is often a critical source of variation in rodent phenotyping and has never been systematically investigated in Pavlovian fear conditioning paradigms. In rodents, fear is typically quantified in terms of freezing duration via...

Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesi...

Synchronized rhythmic network activities are considered key elements of brain function and have been associated with sensory information processing, mnemonic functions and expression of distinct behavioral states. Through their coordinated effects on brain activity patterns, they appear to be particularly well-suited to support the formation and se...

Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the phys...

Theta power throughout the experiment. (A) Theta power in response to presentation of the CS+ for all recording sites and all sessions. Each horizontal line represents a data segment from one animal during the respective session. Dark blue horizontal lines represent data segments that did not survive artifact rejection and were therefore not includ...

Simultaneously recorded LFP and unit activity in CA1 (upper row), LA (middle row), and mPFC (bottow row). (A) CS+ - related activity. Peri-stimulus raster of activity in identified units, calculated 10 seconds before and during CS+ presentation (stimulus onset at time zero). Histograms are averages of activity during 4 consecutive CS+ presentations...

Effects of CA1-LA microstimulation “in-phase” on electrical activity in LA and CA1 (A), on correlation between LA and CA1 (B) and on freezing in non fear-conditioned controls (C). (A) Representative time frequency spectrograms and cross-correlograms of CA1 and LA activity at baseline before (20 s prior to the first CS- presentation) and following m...

Signals related to fear memory and extinction are processed within brain pathways involving the lateral amygdala (LA) for formation of aversive stimulus associations, the CA1 area of the hippocampus for context-dependent modulation of these associations, and the infralimbic region of the medial prefrontal cortex (mPFC) for extinction processes. Whi...

The relationship between epilepsy and fear has received much attention. However, seizure-modulated fear and physiologic or structural correlates have not been examined systematically, and the underlying basics of network levels remain unclear to date. Therefore, this project was set up to characterize the neurophysiologic basis of seizure-related f...

In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Gα(q) knockout on the background of a constitutive Gα(11) knockout (Gα(q)/Gα(11) (-/-)) was used to determine the contribution of Gq/G11 family G-proteins to metabotropic serotonin (5-HT) and glutamate (Glu) func...

Because results from both animal models and human temporal lobe epilepsy (TLE) have pointed to synaptic network alterations in the amygdala, we have tested the hypothesis that glutamatergic transmission in the lateral amygdala (LA) is critically involved. Using the pilocarpine mouse model, LA slices were prepared ex vivo in the recurrent phase of T...

The recently discovered Neuropeptide S (NPS) and its cognate receptor represent a highly interesting system of neuromodulation with unique physiological effects. On one hand, NPS increases wakefulness and arousal. On the other, NPS produces anxiolytic-like effects by acutely reducing fear responses as well as modulating long-term aspects of fear me...

Extinction procedures are clinically relevant for reducing pathological fear, and the mechanisms of fear regulation are a subject of intense research. The amygdala, hippocampus, and prefrontal cortex (PFC) have all been suggested to be key brain areas in extinction of conditioned fear. GABA has particularly been implicated in extinction learning, a...

Zusammenfassung Das vor wenigen Jahren entdeckte Neuropeptid S stellt zusammen mit seinem Rezeptor ein hochinteressantes System der Neuromodulation mit einzigartigem Wirkungsspektrum dar. NPS steigert zum einen Wachheit und Aufmerksamkeit. Das NPS-System wirkt zum anderen anxiolytisch (angstlösend), sowohl akut auf Ängstlichkeit als auch anhaltend...

The recently discovered Neuropeptide S represents - together with its cognate receptor - a highly interesting system of neuromodulation with a unique spectrum of effects. On one hand, NPS promotes wakefulness and arousal. On the other, NPS produces anxiolytic (fear reducing) effects, both on acute fear expression as well as persistent effects on sp...

In this paper, we describe a dynamic causal model (DCM) of steady-state responses in electrophysiological data that are summarised in terms of their cross-spectral density. These spectral data-features are generated by a biologically plausible, neural-mass model of coupled electromagnetic sources; where each source comprises three sub-populations....

A genetic knock out was used to determine the specific contribution of Gq/G11-family G-proteins to the function of thalamocortical relay (TC) neurons. Disruption of Gαq function in a conditional forebrain-specific Gαq/Gα11-double-deficient mouse line $\left( {{{{\text{G $\left( {{{{\text{G had no effects on the resting membrane potential (V rest) a...

A deficient extinction of memory is particularly important in the regime of fear, where it limits the beneficial outcomes of treatments of anxiety disorders. Fear extinction is thought to involve inhibitory influences of the prefrontal cortex on the amygdala, although the detailed synaptic mechanisms remain unknown. Here, we report that neuropeptid...

Channel blocking, anti-oscillatory, and anti-epileptic effects of clinically used anti-absence substances (ethosuximide, valproate) and the T-type Ca2+ current (IT) blocker mibefradil were tested by analyzing membrane currents in acutely isolated local circuit interneurons and thalamocortical relay (TC) neurons, slow intrathalamic oscillations in b...

We have recently demonstrated high theta-phase synchronization between the lateral amygdala and CA1 area of the hippocampus during retrieval of long-term (1 day) fear memory, and not during short-term (2 h) or remote memory retrieval (30 days). These results indicated that the amygdalo-hippocampal interaction reflects a dynamic change of ensemble a...

The amygdala and the hippocampus are critically involved in the formation and retention of fear memories. However, their precise contribution to, and their interplay during, fear memory formation are not fully understood. In the present study we investigated network activities in the amygdalo-hippocampal system of freely behaving mice at different...

A genetic knockout was used to determine the specific contribution of TWIK-related acid-sensitive K+ (TASK)-1 channels to the function of dorsal lateral geniculate nucleus (DLG) thalamocortical relay (TC) neurons. Disruption of TASK-1 function produced an approximately 19% decrease in amplitude of the standing outward current (ISO) and a 3 +/- 1-mV...

Neuronal activity results in significant pH shifts in neurons, glia, and interstitial space. Several transport mechanisms are involved in the fine-tuning and regulation of extra- and intracellular pH. The sodium-independent electroneutral anion exchangers (AEs) exchange intracellular bicarbonate for extracellular chloride and thereby lower the intr...

Zusammenfassung Die Neurone des Thalamus erfüllen zwei Hauptaufgaben während unterschiedlicher Funktionszustände des Gehirns. Während Phasen der Wachheit und erhöhter Aufmerksamkeit generieren die thalamischen Neurone tonische Folgen von Aktionspotentialen, wodurch die eintreffenden sensorischen Signale von der Peripherie (Auge, Ohr, Haut...) getre...

Neurons in the thalamus fulfill two important tasks during different functional states of the brain. During periods of wakefulness and increased arousal, thalamic neurons generate tonic series of action potentials, thereby enabling the faithful transfer of incoming sensory signals from the periphery (eye, ear, skin...) to the cerebral cortex for fi...

With a combined in vitro/in vivo electrophysiological and behavioral approach, we have correlated conditioned fear behavior to electrophysiological activities in the lateral amygdala and the hippocampal formation in rodents. Data indicate that projection neurons in the lateral amygdala display a continuum of spike patterns including accommodating p...

Stimulation of amygdaloid nuclei and emotionally relevant stimuli are known to influence the induction and maintenance of long-term potentiation in the hippocampal formation and the formation of long-term declarative memories. Because the thalamic projection from the posterior paralaminar thalamic nuclei is an important sensory afferent projection...

K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gen...

The amygdalohippocampal circuit plays a pivotal role in Pavlovian fear memory. We simultaneously recorded electrical activity in the lateral amygdala (LA) and the CA1 area of the hippocampus in freely behaving fear-conditioned mice. Patterns of activity were related to fear behavior evoked by conditioned and indifferent sensory stimuli and contexts...

The amygdala is considered a core structure of the so-called limbic system and has been implicated in a variety of functions, including emotional interpretation of sensory information, emotional arousal, emotional memory, fear and anxiety, and related clinical disorders. Despite the clinical and functional importance of the amygdala, it is only rec...

The basolateral amygdala (BLA) can influence distinct learning and memory formation. Hippocampal long-term potentiation (LTP), the most prominent cellular model of memory formation, can be modulated by stimulation of the BLA in its induction and early maintenance. However, it is not known how the late maintenance of LTP beyond its initial phases mi...

In an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neuro...

In a rat model of generalized absence epilepsies (Genetic Absence Epilepsy Rats from Strasbourg, GAERS), multiunit activity was recorded simultaneously at different sites of the thalamocortical system under neurolept anaesthesia (fentanyl-droperidol). Under these conditions, bilaterally synchronized spike-and-wave-discharges (SWDs) occurred spontan...

Current theories on the encoding and storage of information in the brain commonly suppose that a short-term memory is converted into a lasting one; thus, it becomes consolidated over time. Within a finite period after training, such a short-term memory can be reinforced by behavioral and humoral stimuli. We have found that, long-term potentiation (...

Long-latency components of event-related potentials (like the P300 or P3) correlate with the ability of subjects to detect and process unexpected, novel or task-relevant events. Task-relevant late positive components were recorded in the neocortex and hippocampus of rats performing an auditory discrimination task, similar to the "odd-ball" paradigm...

The distribution of the enzyme nitric oxide synthase (NOS) was investigated at the ultrastructural level in synaptic structures of the hippocampal formation in relation to long-term potentiation (LTP), based on the histochemical NADPH-diaphorase (NADPH-d) staining with the tetrazolium salt BSPT. BSPT-formazan, the osmiophilic reaction product, was...

Hippocampal long-term potentiation may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal long-term potentiation in the CA1 region and in the dentate gyrus exhibits distinct phases. These comprise a short-term early potentiation which lasts one to three...

The role of different behavioral states was tested with respect to induction and duration of long-term potentiation (LTP), using strong or weak tetanic stimuli of the perforant path input to the dentate gyrus of freely moving male Wistar rats. Recording and stimulating electrodes were chronically implanted into the granule cell layer of dentate gyr...

Rats with chronically implanted electrodes in the hippocampal CA1 region were tested in their capacity to express and maintain long-term potentiation (LTP) of the population spike (PS) or of the field excitatory postsynaptic potential (fEPSP). Two different states were compared: a) freely moving animals; b) urethane-anesthetized animals (1 g/kg, IP...

The study was conducted to test whether CLIP [ACTH(18-39)] influences the neuronal transmission and the induction of long-term potentiation (LTP) in the hippocampus. The population spike was recorded in the hippocampal CA1 region of freely moving rats before and after intracerebroventricular (ICV) administration of CLIP in comparison to ACTH and sa...

In anaesthetized rats the baroreflex was checked before and 15 min after i.c.v. administration of 10 micrograms SP. The baroreflex was checked indirectly by relating both the reflex prolongation in heart period (inter-beat-interval: IBI) and the reflex inhibition of SNA to a pharmacologically induced BP rise. After i.c.v. administration of SP (n =...

Diss. - Bibliogr. s. 71-96