Kv12-encoded K+ channels drive the day-night switch in the repetitive firing rates of SCN neurons.

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.

Effects of NALCN-Encoded Na Leak Currents on the Repetitive Firing Properties of SCN Neurons Depend on K-Driven Rhythmic Changes in Input Resistance.

Neurons in the suprachiasmatic nucleus (SCN) generate circadian changes in the rates of spontaneous action potential firing that regulate and synchronize daily rhythms in physiology and behavior. Considerable evidence suggests that daily rhythms in the repetitive firing rates (higher during the day than at night) of SCN neurons are mediated by changes in subthreshold potassium (K) conductance(s). An alternative "bicycle" model for circadian regulation of membrane excitability in clock neurons, however, suggests that an increase in NALCN-encoded sodium (Na) leak conductance underlies daytime increases in firing rates.

Kv12-Encoded K Channels Drive the Day-Night Switch in the Repetitive Firing Rates of SCN Neurons.

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K ) channels regulate daily oscillations in the rates of spontaneous action potential firing of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K conductance(s) driving these daily rhythms in repetitive firing rates, however, have not been identified. To test the hypothesis that subthreshold Kv12.

Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 2: Population and Clinical Considerations.

Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD.

Understanding Circadian Mechanisms of Sudden Cardiac Death: A Report From the National Heart, Lung, and Blood Institute Workshop, Part 1: Basic and Translational Aspects.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death.

Entrainment of Circadian Rhythms Depends on Firing Rates and Neuropeptide Release of VIP SCN Neurons.

The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over 3 days.

Acute Knockdown of Kv4.1 Regulates Repetitive Firing Rates and Clock Gene Expression in the Suprachiasmatic Nucleus and Daily Rhythms in Locomotor Behavior.

Rapidly activating and inactivating A-type K currents (I) encoded by Kv4.2 and Kv4.3 pore-forming (α) subunits of the Kv4 subfamily are key regulators of neuronal excitability.

Distinct Firing Properties of Vasoactive Intestinal Peptide-Expressing Neurons in the Suprachiasmatic Nucleus.

The suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behavior. Previous studies suggest a critical role for neurons expressing vasoactive intestinal peptide (VIP) in coordinating rhythmicity and synchronization in the SCN. Here we examined the firing properties of VIP-expressing SCN neurons in acute brain slices.

IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus.

Neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals, display daily rhythms in electrical activity with more depolarized resting potentials and higher firing rates during the day than at night. Although these daily variations in the electrical properties of SCN neurons are required for circadian rhythms in physiology and behavior, the mechanisms linking changes in neuronal excitability to the molecular clock are not known. Recently, we reported that mice deficient for either Kcna4 (Kv1.

Generation of human striatal neurons by microRNA-dependent direct conversion of fibroblasts.

The promise of using reprogrammed human neurons for disease modeling and regenerative medicine relies on the ability to induce patient-derived neurons with high efficiency and subtype specificity. We have previously shown that ectopic expression of brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), promoted direct conversion of human fibroblasts into neurons. Here we show that coexpression of miR-9/9*-124 with transcription factors enriched in the developing striatum, BCL11B (also known as CTIP2), DLX1, DLX2, and MYT1L, can guide the conversion of human postnatal and adult fibroblasts into an enriched population of neurons analogous to striatal medium spiny neurons (MSNs).

Kv2.2: a novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep-wake cycle.

Study Objectives: The basal forebrain (BF) has been implicated as an important brain region that regulates the sleep-wake cycle of animals. Gamma-aminobutyric acidergic (GABAergic) neurons are the most predominant neuronal population within this region. However, due to the lack of specific molecular tools, the roles of the BF GABAergic neurons have not been fully elucidated.

Immunolocalization of the voltage-gated potassium channel Kv2.2 in GABAergic neurons in the basal forebrain of rats and mice.

The Kv2 voltage-gated potassium channels, Kv2.1 and Kv2.2, are important regulators of neuronal excitability in mammalian brain.

Formation of heteromeric Kv2 channels in mammalian brain neurons.

The formation of heteromeric tetramers is a common feature of voltage-gated potassium (Kv) channels. This results in the generation of a variety of tetrameric Kv channels that exhibit distinct biophysical and biochemical characteristics. Kv2 delayed rectifier channels are, however, unique exceptions.

An operant conditioning model to assess changes in feeding behavior associated with temporomandibular joint inflammation in the rat.

Aims: To develop and validate a model in which to assess a loss of function associated with temporomandibular joint (TMJ) inflammation in awake, freely moving rats.

Methods: The dependent variable in the model was the time between food rewards (pellets), or interfeeding interval (IFI). IFI was quantified after rats were trained to "bar-press" for food.

Testosterone and estrogen have opposing actions on inflammation-induced plasma extravasation in the rat temporomandibular joint.

The present study was designed to test the hypothesis that estrogen exacerbates inflammation of the temporomandibular joint (TMJ). Evans blue dye was used to quantify plasma extravasation (PE) around the rat TMJ. In an initial set of experiments, TMJ PE was compared in naïve intact male and female rats, as well as in both groups after complete Freund's adjuvant (CFA)-induced inflammation of the TMJ.