In the cerebral cortex, GABAergic interneurons are often regarded as fast-spiking cells. We have identified a type of slow-spiking interneuron that offers distinct contributions to network activity. "Ivy" cells, named after their dense and fine axons innervating mostly basal and oblique pyramidal cell dendrites, are more numerous than the parvalbumin-expressing basket, bistratified, or axo-axonic cells. Ivy cells express nitric oxide synthase, neuropeptide Y, and high levels of GABA(A) receptor alpha1 subunit; they discharge at a low frequency with wide spikes in vivo, yet are distinctively phase-locked to behaviorally relevant network rhythms including theta, gamma, and ripple oscillations. Paired recordings in vitro showed that Ivy cells receive depressing EPSPs from pyramidal cells, which in turn receive slowly rising and decaying inhibitory input from Ivy cells. In contrast to fast-spiking interneurons operating with millisecond precision, the highly abundant Ivy cells express presynaptically acting neuromodulators and regulate the excitability of pyramidal cell dendrites through slowly rising and decaying GABAergic inputs.
Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.
Decision-making can be supported by incorporating families into discussions regarding epilepsy surgery as a potential treatment option earlier in the process and by providing families with additional information and access to other parents with similar experiences.
The prevalence of GDM in rural Bangladesh is comparable with any other population with higher prevalence of GDM. Increased morbidity and mortality among mothers and newborns in Bangladesh may, in part, be because of increased prevalence of GDM.
BackgroundAtopic dermatitis (AD) is a chronic relapsing allergic inflammatory skin disease that currently affects millions of children and adults worldwide. Drugs used to treat these inflammatory diseases include anti-histamines, corticosteroids and calcineurin inhibitors but these drugs have their limitations such as adverse effects with their long-term usage. Thus, researcher’s interest in several alternative and complementary therapies are continually growing and balneotherapy is one of these approaches. Therefore, we investigate the bathing effect of high concentration mineral spring water (HMW) on redox balance and immune modulation in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis like inflammation in hairless mice.MethodsWe induced AD-like inflammation by application of DNCB on the dorsal skin of female skh-1 hairless mice. The mice were treated with 100% pure HMW (PHMW) and 10% diluted HMW (DHMW) through bathing once a day for 4 weeks. Tacrolimus ointment (0.1%) was used as positive control (PC) and only DNCB treatment as negative control (NeC) group. The severity of skin lesion inflammation was assessed through clinical scoring and observing scratching behavior. Levels of immunoglobulin E (IgE) and inflammatory cytokines in serum were detected by ELISA and multiplex bead array system, and the levels of oxidative stress-related biomarkers and antioxidant enzyme were also measured.ResultsWe found that HMW significantly decreased the scratching behavior in PHMW and DHMW groups at the 2nd week and in PHMW group at 4th week compared to NeC group. Likewise, serum IgE level was significantly decreased in DHMW group as compared to NeC group. In line, the level of inflammatory cytokines in serum such as interleukin (IL)-1β, IL-13 and tumor necrosis factor-α were significantly inhibited in PHMW and DHMW groups compared to NeC group. In parallel, total reactive oxygen species (ROS) of serum level was significantly decreased in PHMW treatment groups compared to NeC group. Consistently, serum malondialdehyde (MDA) level in PHMW group was lower than in NeC group. By contrast, glutathione peroxidase (GPx) activity was significantly enhanced in PHMW than NeC.ConclusionCollectively, our study indicates a balneotherapeutic effect of HMW on DNCB-induced AD like inflammation in hairless mice via immunomodulation and redox balance.
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