Early establishment of chloride homeostasis in CRH neurons is altered by prenatal stress leading to fetal HPA axis dysregulation.

Corticotropin-releasing hormone (CRH) neurons play an important role in the regulation of neuroendocrine responses to stress. The excitability of CRH neurons is regulated by inhibitory GABAergic inputs. However, it is unclear when GABAergic regulation of CRH neurons is established during fetal brain development.

Static Magnetic Field Stimulation Enhances Shunting Inhibition via a SLC26 Family Cl Channel, Inducing Intrinsic Plasticity.

Magnetic fields are being used for detailed anatomical and functional examination of the human brain. In addition, evidence for their efficacy in treatment of brain dysfunctions is accumulating. Transcranial static magnetic field stimulation (tSMS) is a recently developed technique for noninvasively modifying brain functions.

Dual action of serotonin on local excitatory and inhibitory neural circuits regulating the corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus.

Serotonergic neurons originating from the raphe nuclei have been proposed to regulate corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVH). Since glutamate- and γ-aminobutyric acid (GABA)-containing neurons, constituting the hypothalamic local circuits, innervate PVH CRF neurons, we examined whether they mediate the actions of serotonin (5-hydroxytryptamine [5-HT]) on CRF neurons. Spontaneous excitatory postsynaptic currents (sEPSCs) or spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in PVH CRF neurons, under whole cell patch-clamp, using the CRF-modified yellow fluorescent protein (Venus) ΔNeo mouse.

Astrocytic NKCC1 inhibits seizures by buffering Cl and antagonizing neuronal NKCC1 at GABAergic synapses.

Objective: A pathological excitatory action of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl concentration ([Cl ] ) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted.

Maternal taurine as a modulator of Cl homeostasis as well as of glycine/GABA receptors for neocortical development.

During brain and spinal cord development, GABA and glycine, the inhibitory neurotransmitters, cause depolarization instead of hyperpolarization in adults. Since glycine and GABA receptors (GABARs) are chloride (Cl) ion channel receptor, the conversion of GABA/glycine actions during development is influenced by changes in the transmembrane Cl gradient, which is regulated by Cl transporters, NKCC1 (absorption) and KCC2 (expulsion). In immature neurons, inhibitory neurotransmitters are released in a non-vesicular/non-synaptic manner, transitioning to vesicular/synaptic release as the neuron matures.

Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons.

Fetal and infant brains are rich in maternally derived taurine. We previously demonstrated that taurine action regulates the cation-chloride cotransporter activity and the differentiation and radial migration of pyramidal neuron progenitors in the developing neocortex of rodent fetuses. Here we examined the effects of fetal and infantile taurine depletion caused by knockout of the taurine transporter Slc6a6 on firing properties of layer II/III pyramidal neurons in the mouse somatosensory cortex at 3 weeks of postnatal age, using the whole-cell patch-clamp technique.

A novel de novo KCNB1 variant altering channel characteristics in a patient with periventricular heterotopia, abnormal corpus callosum, and mild seizure outcome.

KCNB1 encodes the α-subunit of Kv2.1, the main contributor to neuronal delayed rectifier potassium currents. The subunit consists of six transmembrane α helices (S1-S6), comprising the voltage-sensing domain (S1-S4) and the pore domain (S5-P-S6).

A subpopulation of agouti-related peptide neurons exciting corticotropin-releasing hormone axon terminals in median eminence led to hypothalamic-pituitary-adrenal axis activation in response to food restriction.

The excitatory action of gamma-aminobutyric-acid (GABA) in the median-eminence (ME) led to the steady-state release of corticotropin-releasing hormone (CRH) from CRH axon terminals, which modulates the hypothalamic-pituitary-adrenal (HPA) axis. However, in ME, the source of excitatory GABAergic input is unknown. We examined agouti-related peptide (AgRP) expressing neurons in the arcuate nucleus as a possible source for excitatory GABAergic input.

Effects of Taurine Depletion on Body Weight and Mouse Behavior during Development.

Taurine (2-aminoethanesulfonic acid) plays an important role in various physiological functions and is abundant in the brain and skeletal muscle. Extracellular taurine is an endogenous agonist of gamma-aminobutyric acid type A and glycine receptors. Taurine actively accumulates in cells via the taurine transporter (TauT).

Orchestration of Ion Channels and Transporters in Neocortical Development and Neurological Disorders.

Electrical activity plays crucial roles in neural circuit formation and remodeling. During neocortical development, neurons are generated in the ventricular zone, migrate to their correct position, elongate dendrites and axons, and form synapses. In this review, we summarize the functions of ion channels and transporters in neocortical development.

Functional MHCI deficiency induces ADHD-like symptoms with increased dopamine D1 receptor expression.

Inappropriate synaptic development has been proposed as a potential mechanism of neurodevelopmental disorders, including attention-deficit hyperactivity disorder (ADHD). Major histocompatibility complex class I (MHCI), an immunity-associated molecule expressed by neurons in the brain, regulates synaptic development; however, the involvement of MHCI in these disorders remains elusive. We evaluated whether functional MHCI deficiency induced by β2mTap1 double-knockout in mice leads to abnormalities akin to those seen in neurodevelopmental disorders.

[Cl-GABA System Underlying Modal Shifts from Cellular to Network Oscillations].

Gamma-aminobutyric acid (GABA) generally induces hyperpolarization and inhibition in the adult brain, but causes depolarization (and can be excitatory) in the immature brain. Because GABA receptors are Cl channels, alternating GABA actions between hyperpolarization (Cl influx) and depolarization (Cl efflux) are induced by changes in the Cl gradient, which is regulated by Cl transporters. Thus, the dynamics of neural functions are modulated by "active" Cl homeostasis (Cl homeodynamics), alternating inhibition and excitation, and could be the underlying mechanism of modal shifts in cellular and network oscillations.

Dielectric study of a subphase stabilized in an exceptionally wide temperature range by a delicate balance of interlayer interactions and thermal fluctuations.

The chiral smectic phases of calamitic liquid crystals, SmC^{*} and SmC_{A}^{*}, are characterized by the synclinic ferroelectric F ordering and the anticlinic antiferroelectric A ordering in adjacent layers. Various states with mixed A and F orderings are degenerate at the frustrated phase-transition point. The degeneracy lifting is commonly caused by the long-range interlayer interactions (LRILIs), producing a series of biaxial subphases specified by a relative ratio of both orderings, q_{T}=[F]/([A]+[F]).

Can we understand human brain development from experimental studies in rodents?

Animal models are needed to gain an understanding of the genetic, molecular, cellular, and network mechanisms of human brain development. In rodents, a large spectrum of in vitro and in vivo approaches allows detailed analyses and specific experimental manipulations for studying the sequence of developmental steps in corticogenesis. Neurogenesis, neuronal migration, cellular differentiation, programmed cell death, synaptogenesis, and myelination are surprisingly similar in the rodent cortex and the human cortex.

Intracellular Cl dysregulation causing and caused by pathogenic neuronal activity.

The intracellular Cl concentration ([Cl]) is tightly regulated in brain neurons for stabilizing brain performance. The [Cl] in mature neurons is determined by the balance between the rate of Cl extrusion mainly mediated by the neuron-specific type 2 K-Cl cotransporter (KCC2) and the rate of Cl entry through various Cl channels including GABA receptors during neuronal activity. Disturbance of the balance causes instability of brain circuit performance and may lead to epileptic seizures.