Exploration of Theta Burst-Induced Modulation of Transcranial Magnetic Stimulation-Evoked Potentials Over the Motor Cortex.

Objectives: This study investigates the way theta burst stimulation (TBS) applied to the motor cortex (M1) affects TMS-evoked potentials (TEPs). There have been few direct comparisons of continuous TBS (cTBS) and intermittent TBS (iTBS), and there is a lack of consensus from existing literature on the induced effects. We performed an exploratory trial to assess the effect of M1-cTBS and M1-iTBS on TEP components.

Increased Dentate Gyrus Excitability in the Intrahippocampal Kainic Acid Mouse Model for Temporal Lobe Epilepsy.

The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model.

In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.

Aims: The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model.

Methods: Rats were bilaterally injected with 0.

Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist.

We report the design, synthesis, and validation of the novel compound photocaged N-cyclopentyladenosine (cCPA) to achieve precisely localized and timed release of the parent adenosine A1 receptor agonist CPA using 405 nm light. G protein-coupled A receptors (ARs) modulate neurotransmission via pre- and post-synaptic routes. The dynamics of the CPA-mediated effect on neurotransmission, characterized by fast activation and slow recovery, make it possible to implement a closed-loop control paradigm.

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males.

Objectives: As a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG.

No persistent effects of intracerebral curcumin administration on seizure progression and neuropathology in the kindling rat model for temporal lobe epilepsy.

Purpose: Curcumin is known for its neuroprotective, anti-inflammatory and anti-oxidant properties and has been investigated as a potential therapeutic drug for Temporal Lobe Epilepsy (TLE). We previously found anti-epileptogenic properties of curcumin in an in vitro brain slice model for epileptogenesis, and inhibitory effects on the MAPK-pathway in vivo after intracerebrally applying curcumin in post-status epilepticus rats. Here, we investigated whether the intracerebral application of curcumin could be anti-epileptogenic in the rapid kindling rat model for TLE.

blue light illumination for optogenetic inhibition: effect on local temperature and excitability of the rat hippocampus.

The blue light-activated inhibitory opsin, stGtACR2, is gaining prominence as a neuromodulatory tool due its ability to shunt-inhibit neurons and is being frequently used inexperimentation. However, experiments involving stGtACR2 use longer durations of blue light pulses, which inadvertently heat up the local brain tissue and confound experimental results. Therefore, the heating effects of illumination parameters used foroptogenetic inhibition must be evaluated.

Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model.

Expression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam (LEV).

Level of hM4D(Gi) DREADD Expression Determines Inhibitory and Neurotoxic Effects in the Hippocampus.

Selective neuromodulation using designer receptors exclusively activated by designer drugs (DREADDs) has become an increasingly important research tool, as well as an emerging therapeutic approach. However, the safety profile of DREADD expression is unknown. Here, different titers of adeno-associated viral (AAV) vector were administered in an attempt to vary total expression levels of the inhibitory DREADD hM4D(Gi) in excitatory hippocampal neurons.

Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer's disease mouse model.

There is increasing evidence of altered tissue mechanics in neurodegeneration. However, due to difficulties in mechanical testing procedures and the complexity of the brain, there is still little consensus on the role of mechanics in the onset and progression of neurodegenerative diseases. In the case of Alzheimer's disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD patients and healthy controls.

White Matter Integrity in a Rat Model of Epileptogenesis: Structural Connectomics and Fixel-Based Analysis.

Electrophysiological and neuroimaging studies have demonstrated that large-scale brain networks are affected during the development of epilepsy. These networks can be investigated by using diffusion magnetic resonance imaging (dMRI). The most commonly used model to analyze dMRI is diffusion tensor imaging (DTI).

Attenuation of Hippocampal Evoked Potentials by Activation of GtACR2, an Optogenetic Chloride Channel.

Aim: GtACR2, a light-activated chloride channel, is an attractive tool for neural inhibition as it can shunt membrane depolarizations. In this study, we assessed the effect of activating GtACR2 on hippocampal CA1 activity evoked by Schaffer collateral (SC) stimulation.

Methods: Adult male Wistar rats were unilaterally injected with 0.

Long-term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy.

Objective: One third of epilepsy patients do not become seizure-free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity.

The matrix metalloproteinase inhibitor IPR-179 has antiseizure and antiepileptogenic effects.

Matrix metalloproteinases (MMPs) are synthesized by neurons and glia and released into the extracellular space, where they act as modulators of neuroplasticity and neuroinflammatory agents. Development of epilepsy (epileptogenesis) is associated with increased expression of MMPs, and therefore, they may represent potential therapeutic drug targets. Using quantitative PCR (qPCR) and immunohistochemistry, we studied the expression of MMPs and their endogenous inhibitors tissue inhibitors of metalloproteinases (TIMPs) in patients with status epilepticus (SE) or temporal lobe epilepsy (TLE) and in a rat TLE model.

Viscoelastic mapping of mouse brain tissue: Relation to structure and age.

There is growing evidence that mechanical factors affect brain functioning. However, brain components responsible for regulating the physiological mechanical environment are not completely understood. To determine the relationship between structure and stiffness of brain tissue, we performed high-resolution viscoelastic mapping by dynamic indentation of the hippocampus and the cerebellum of juvenile mice brains, and quantified relative area covered by neurons (NeuN-staining), axons (neurofilament NN18-staining), astrocytes (GFAP-staining), myelin (MBP-staining) and nuclei (Hoechst-staining) of juvenile and adult mouse brain slices.

Development of a Rat Model for Glioma-Related Epilepsy.

Seizures are common in patients with high-grade gliomas (30-60%) and approximately 15-30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex.

Acute symptomatic seizures following intracerebral hemorrhage in the rat collagenase model.

Background And Purpose: Intracerebral hemorrhage (ICH) is a known risk factor for the development of seizures, but little is known about the pathophysiology of seizures in the acute phase post-ICH and their influence on functional outcome. With the use of an animal model, the underlying pathophysiology could be further unraveled. The aim of our study was to optimize the rat collagenase stroke model for the detection of acute symptomatic seizures using video-EEG monitoring.

Identification of vagus nerve stimulation parameters affecting rat hippocampal electrophysiology without temperature effects.

Background: Recent experiments in rats have demonstrated significant effects of VNS on hippocampal excitability but were partially attributed to hypothermia, induced by the applied VNS parameters.

Objective: To allow meaningful preclinical research on the mechanisms of VNS and translation of rodent results to clinical VNS trials, we aimed to identify non-hypothermia inducing VNS parameters that significantly affect hippocampal excitability.

Methods: VNS was administered in cycles of 30 s including either 0.

Deep brain stimulation reduces evoked potentials with a dual time course in freely moving rats: Potential neurophysiological basis for intermittent as an alternative to continuous stimulation.

Objective: Deep brain stimulation (DBS) is an increasingly applied treatment for various neuropsychiatric disorders including drug-resistant epilepsy, and it may be optimized by rationalizing the stimulation protocol based on increased knowledge of its mechanism of action. We evaluated the effects of minutes to hours of hippocampal DBS on hippocampal evoked potentials (EPs) and local field potentials (LFPs) in freely moving male rats to further investigate some of the previously proposed mechanisms of action.

Methods: Hippocampal high-frequency (130 Hz) DBS was administered for 0, 1, or 6 min every 10 min for 160 min.

A Feasibility Study to Investigate Chemogenetic Modulation of the Locus Coeruleus by Means of Single Unit Activity.

Aim: Selective chemogenetic modulation of locus coeruleus (LC) neurons would allow dedicated investigation of the role of the LC-NA pathway in brain excitability and disorders such as epilepsy. This study investigated the feasibility of an experimental set-up where chemogenetic modification of the brainstem locus coeruleus NA neurons is aimed at and followed by LC unit activity recording in response to clozapine.

Methods: The LC of male Sprague-Dawley rats was injected with 10 nl of adeno-associated viral vector AAV2/7-PRSx8-hM3Dq-mCherry ( = 19, DREADD group) or AAV2/7-PRSx8-eGFP ( = 13, Controls).

Resonance in the Mouse Ventral Tegmental Area Dopaminergic Network Induced by Regular and Poisson Distributed Optogenetic Stimulation .

Neurons in many brain regions exhibit spontaneous, intrinsic rhythmic firing activity. This rhythmic firing activity may determine the way in which these neurons respond to extrinsic synaptic inputs. We hypothesized that neurons should be most responsive to inputs at the frequency of the intrinsic oscillation frequency.

Long-term chemogenetic suppression of spontaneous seizures in a mouse model for temporal lobe epilepsy.

Objective: More than one-third of patients with temporal lobe epilepsy (TLE) continue to have seizures despite treatment with antiepileptic drugs, and many experience severe drug-related side effects, illustrating the need for novel therapies. Selective expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allows cell-type-specific reduction of neuronal excitability. In this study, we evaluated the effect of chemogenetic suppression of excitatory pyramidal and granule cell neurons of the sclerotic hippocampus in the intrahippocampal mouse model (IHKA) for temporal lobe epilepsy.

Interaction of Cortical and Amygdalar Synaptic Input Modulates the Window of Opportunity for Information Processing in the Rhinal Cortices.

The perirhinal (PER) and lateral entorhinal (LEC) cortex function as a gateway for information transmission between (sub)cortical areas and the hippocampus. It is hypothesized that the amygdala, a key structure in emotion processing, can modulate PER-LEC neuronal activity before information enters the hippocampal memory pathway. This study determined the integration of synaptic activity evoked by simultaneous neocortical and amygdala electrical stimulation in PER-LEC deep layer principal neurons and parvalbumin (PV) interneurons in mouse brain slices.

Modulation of Functional Connectivity Between Dopamine Neurons of the Rat Ventral Tegmental Area .

Micro Electrode Arrays were used to simultaneously record spontaneous extracellular action potentials from 10 to 30 dopamine neurons in acute brain slices from the lateral Ventral Tegmental Area (VTA) of the rat. The spike train of an individual neuron was used to characterize the firing pattern: firing rate, firing irregularity and oscillation frequency. Functional connectivity between a pair of neurons was quantified by the Paired Phase Consistency (PPC), taking the oscillation frequency as reference.

Excitation-Inhibition Dynamics Regulate Activity Transmission Through the Perirhinal-Entorhinal Network.

The perirhinal (PER) - lateral entorhinal (LEC) network plays a pivotal role in the information transfer between the neocortex and the hippocampus. Anatomical studies have shown that the connectivity is organized bi-directionally: the superficial layers consist of projections running from the neocortex via the PER-LEC network to the hippocampus while the deep layers form the output pathway back to the neocortex. Although these pathways are characterized anatomically, the functional organization of the superficial and deep connections in the PER-LEC network remains to be revealed.