Digital reconstruction of infraslow activity in human intracranial ictal recordings using a deconvolution-based inverse filter.

Infraslow activity (ISA) is a biomarker that has recently become of interest in the characterization of seizure recordings. Recent data from a small number of studies have suggested that the epileptogenic zone may be identified by the presence of ISA. Investigation of low frequency activity in clinical seizure recordings, however, has been hampered by technical limitations.

Developmental defects and impaired network excitability in a cerebral organoid model of KCNJ11 p.V59M-related neonatal diabetes.

The gene KCNJ11 encodes Kir6.2 a major subunit of the ATP-sensitive potassium channel (K) expressed in both the pancreas and brain. Heterozygous gain of function mutations in KCNJ11 can cause neonatal diabetes mellitus (NDM).

Transparent, Compliant 3D Mesostructures for Precise Evaluation of Mechanical Characteristics of Organoids.

Recently developed methods for transforming 2D patterns of thin-film materials into 3D mesostructures create many interesting opportunities in microsystems design. A growing area of interest is in multifunctional thermal, electrical, chemical, and optical interfaces to biological tissues, particularly 3D multicellular, millimeter-scale constructs, such as spheroids, assembloids, and organoids. Herein, examples of 3D mechanical interfaces are presented, in which thin ribbons of parylene-C form the basis of transparent, highly compliant frameworks that can be reversibly opened and closed to capture, envelop, and mechanically restrain fragile 3D tissues in a gentle, nondestructive manner, for precise measurements of viscoelastic properties using techniques in nanoindentation.

Role of paroxysmal depolarization in focal seizure activity.

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery.

Activation of Dopamine Receptor 2 Prompts Transcriptomic and Metabolic Plasticity in Glioblastoma.

Glioblastoma (GBM) is one of the most aggressive and lethal tumor types. Evidence continues to accrue indicating that the complex relationship between GBM and the brain microenvironment contributes to this malignant phenotype. However, the interaction between GBM and neurotransmitters, signaling molecules involved in neuronal communication, remains incompletely understood.

Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex.

High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach.

Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents.

The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while short-timescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Nap) currents govern burst onset during interburst intervals.

Modeling focal epileptic activity in the Wilson-cowan model with depolarization block.

Unlabelled: Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate.

TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

Memory formation requires de novo protein synthesis, and memory disorders may result from misregulated synthesis of critical proteins that remain largely unidentified. Plasma membrane ion channels and receptors are likely candidates given their role in regulating neuron excitability, a candidate memory mechanism. Here we conduct targeted molecular monitoring and quantitation of hippocampal plasma membrane proteins from mice with intact or impaired contextual fear memory to identify putative candidates.

Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature.

Mammals have circadian variation in blood pressure, heart rate, vascular tone, thrombotic tendency, and cerebral blood flow (CBF). These changes may be in part orchestrated by circadian variation in clock gene expression within cells comprising the vasculature that modulate blood flow (e.g.

Metabotropic glutamate receptors (mGluR5) activate transient receptor potential canonical channels to improve the regularity of the respiratory rhythm generated by the pre-Bötzinger complex in mice.

Metabotropic glutamate receptors (mGluRs) are hypothesized to play a key role in generating the central respiratory rhythm and other rhythmic activities driven by central pattern generators (e.g. locomotion).

Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric patients with epilepsy.

Neocortical oscillations result from synchronized activity of a synaptically coupled network and can be strongly influenced by the intrinsic firing properties of individual neurons. As such, the intrinsic electroresponsive properties of individual neurons may have important implications for overall network function. Rhythmic intrinsic bursting (rIB) neurons are of particular interest, as they are poised to initiate and/or strongly influence network oscillations.

Neuronal bursting properties in focal and parafocal regions in pediatric neocortical epilepsy stratified by histology.

To test the hypothesis that focal and parafocal neocortical tissue from pediatric patients with intractable epilepsy exhibits cellular and synaptic differences, the authors characterized the propensity of these neurons to generate (a) voltage-dependent bursting and (b) synaptically driven paroxysmal depolarization shifts. Neocortical slices were prepared from tissue resected from patients with intractable epilepsy. Multiunit network activity and simultaneous whole-cell patch recordings were made from neurons from three patient groups: (1) those with normal histology; (2) those with mild and severe cortical dysplasia; and (3) those with abnormal pathology but without cortical dysplasia.

Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN-dependent pacemaker activity.

Neuromodulators, such as substance P (SubP), play an important role in modulating many rhythmic activities driven by central pattern generators (e.g. locomotion, respiration).

Bioaminergic neuromodulation of respiratory rhythm in vitro.

Bioamines, such as norepinephrine and serotonin are key neurotransmitters implicated in multiple physiological and pathological brain mechanisms. Evolutionarily, the bioaminergic neuromodulatory system is widely distributed throughout the brain and is among the earliest neurotransmitters to arise within the hindbrain. In both vertebrates and invertebrates, monoamines play a critical role in the control of respiration.

Background sodium current underlying respiratory rhythm regularity.

Rhythm-generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states--thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or 'stable' respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing.

Differential modulation of neural network and pacemaker activity underlying eupnea and sigh-breathing activities.

Many networks generate distinct rhythms with multiple frequency and amplitude characteristics. The respiratory network in the pre-Bötzinger complex (pre-Böt) generates both the low-frequency, large-amplitude sigh rhythm and a faster, smaller-amplitude eupneic rhythm. Could the same set of pacemakers generate both rhythms? Here we used an in vitro respiratory brainslice preparation.

Gasping activity in vitro: a rhythm dependent on 5-HT2A receptors.

Many rhythmic behaviors are continuously modulated by endogenous peptides and amines, but whether neuromodulation is critical to the expression of a rhythmic behavior often remains unknown, particularly in mammals. Here, we address this issue in the respiratory network that was isolated in spontaneously rhythmic medullary slice preparations from mice. Under control conditions, the respiratory network generates fictive eupneic activity.

Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice.

Rett syndrome is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein 2 (MECP2) gene and suffer from bioaminergic deficiencies and life-threatening breathing disturbances. We used in vivo plethysmography, in vitro electrophysiology, neuropharmacology, immunohistochemistry, and biochemistry to characterize the consequences of the MECP2 mutation on breathing in wild-type (wt) and Mecp2-deficient (Mecp2-/y) mice. At birth, Mecp2-/y mice showed normal breathing and a normal number of medullary neurons that express tyrosine hydroxylase (TH neurons).

Pacemaker neurons and neuronal networks: an integrative view.

Rhythmically active neuronal networks give rise to rhythmic motor activities but also to seemingly non-rhythmic behaviors such as sleep, arousal, addiction, memory and cognition. Many of these networks contain pacemaker neurons. The ability of these neurons to generate bursts of activity intrinsically lies in voltage- and time-dependent ion fluxes resulting from a dynamic interplay among ion channels, second messenger pathways and intracellular Ca2+ concentrations, and is influenced by neuromodulators and synaptic inputs.

Background sodium current stabilizes bursting in respiratory pacemaker neurons.

Endogenous pacemaker properties have been proposed to generate rhythmic activity underlying many behaviors including respiration. For pacemakers to generate regenerative bursting, background currents maintain their membrane potential (Vm) within a range where bi-stable properties are expressed, thereby stabilizing rhythmogenesis. We previously found that the baseline Vm of respiratory pacemakers is stabilized against hyperpolarizing shifts in their Vm.

Differential contribution of pacemaker properties to the generation of respiratory rhythms during normoxia and hypoxia.

Pacemaker neurons have been described in most neural networks. However, whether such neurons are essential for generating an activity pattern in a given preparation remains mostly unknown. Here, we show that in the mammalian respiratory network two types of pacemaker neurons exist.

Hyperthermia modulates respiratory pacemaker bursting properties.

Most mammals modulate respiratory frequency (RF) to dissipate heat (e.g., panting) and avoid heat stroke during hyperthermic conditions.

Stabilization of bursting in respiratory pacemaker neurons.

Synaptic and endogenous pacemaker properties have been hypothesized as principal cellular mechanisms for respiratory rhythm generation. This rhythmic activity is thought to originate in the pre-Bötzinger complex, an area that can generate fictive respiration when isolated in brainstem slice preparations of mice. In slice preparations, external potassium concentration ([K+]o) is typically elevated from 3 to 8 mm to induce rhythmic population activity.