Age-related changes in Kv4/Shal and Kv1/Shaker expression in Drosophila and a role for reactive oxygen species.

Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects Kv4/Shal and Kv1/Shaker K+ channel protein levels in Drosophila. We show that Kv4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion.

Slo2/K Channels in Protect against Spontaneous and Induced Seizure-like Behavior Associated with an Increased Persistent Na Current.

Na sensitivity is a unique feature of Na-activated K (K) channels, making them naturally suited to counter a sudden influx in Na ions. As such, it has long been suggested that K channels may serve a protective function against excessive excitation associated with neuronal injury and disease. This hypothesis, however, has remained largely untested.

Cholinergic Synaptic Homeostasis Is Tuned by an NFAT-Mediated α7 nAChR-K4/Shal Coupled Regulatory System.

Homeostatic synaptic plasticity (HSP) involves compensatory mechanisms employed by neurons and circuits to preserve signaling when confronted with global changes in activity that may occur during physiological and pathological conditions. Cholinergic neurons, which are especially affected in some pathologies, have recently been shown to exhibit HSP mediated by nicotinic acetylcholine receptors (nAChRs). In Drosophila central neurons, pharmacological blockade of activity induces a homeostatic response mediated by the Drosophila α7 (Dα7) nAChR, which is tuned by a subsequent increase in expression of the voltage-dependent K4/Shal channel.

Cholinergic Homeostatic Synaptic Plasticity Drives the Progression of Aβ-Induced Changes in Neural Activity.

Homeostatic synaptic plasticity (HSP) is the ability of neurons to exert compensatory changes in response to altered neural activity. How pathologically induced activity changes are intertwined with HSP mechanisms is unclear. We show that, in cholinergic neurons from Drosophila, beta-amyloid (Aβ) peptides Aβ40 and Aβ42 both induce an increase in spontaneous activity.

Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer's model.

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. β-amyloid (Aβ) accumulation in the brain is thought to be a primary event leading to eventual cognitive and motor dysfunction in AD. Aβ has been shown to promote neuronal hyperactivity, which is consistent with enhanced seizure activity in mouse models and AD patients.

GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain.

Background: Neuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.

A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons.

The relative contribution to brain cholinergic signaling by synaptic- and diffusion-based mechanisms remains to be elucidated. In this study, we examined the prevalence of fast nicotinic signaling in the hippocampus. We describe a mouse model where cholinergic axons are labeled with the tauGFP fusion protein driven by the choline acetyltransferase promoter.

Substance P induces the reversible formation of varicosities in the dendrites of rat brainstem neurons.

This study investigated the ability of substance P (Sub P) to induce dendritic varicosities (DVs) or beads in neurons of the rostral ventromedial medulla (RVM) of the rat. Microinjection of 5-200 pmol Sub P in the RVM produced a concentration-dependent increase in the number of DVs in distal dendrites of RVM neurons that were immunoreactive for the neurokinin-1 receptor, but not serotonin. The effect was reversible, as DVs were essentially absent 2 and 4h after microinjection.

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons.

Reactive oxygen species (ROS), which include hydrogen peroxide (H(2)O(2)), the superoxide anion (O(2) (-).), and the hydroxyl radical (OH.), are generated as by-products of oxidative metabolism in cells.

5-HT1A receptor-mediated activation of a G-protein-coupled inwardly rectifying K+ current in rat medial preoptic area neurons.

The medial preoptic area plays an important role in the regulation of sexual behavior, and serotonin (5-hydroxytryptamine, 5-HT) exerts an inhibitory effect on sexual behavior by acting on the medial preoptic area region. This study was designed to clarify the inhibitory effect of 5-HT on the medial preoptic area neurons and to elucidate the electrophysiological mechanisms involved in the action of 5-HT. Superfusion of 100 nM 5-HT hyperpolarized the membrane potential and inhibited the action potential firing.

Serotonergic modulation of GABAergic and glutamatergic synaptic transmission in mechanically isolated rat medial preoptic area neurons.

The medial preoptic area (MPOA) of the hypothalamus is critically involved in the regulation of male sexual behavior and has been implicated in several homeostatic processes. Serotonin (5-hydroxytryptamine, 5-HT) inhibits sexual behavior via effects in the MPOA, where there are high densities of 5-HT(1A) and 5-HT(1B) receptor subtypes. We used whole-cell recordings under voltage-clamp conditions to investigate the serotonergic modulation of gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission in mechanically dissociated rat MPOA neurons with native presynaptic nerve endings.

Developmental change of GABAergic postsynaptic current in rat periaqueductal gray.

The present study was designed to examine developmental changes of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in periaqueductal gray (PAG) neurons mechanically isolated from young (12- to 18-day) and adult (8- to 12-week) rats. While the frequency of mIPSCs was similar, the current amplitude in adult rats was significantly smaller than in young rats. In the study of mIPSC kinetics, all kinetic parameters except for the fast decay time in adult rats were smaller or shorter than in the case of young rats.

Opioid inhibition of GABAergic neurotransmission in mechanically isolated rat periaqueductal gray neurons.

The descending pain control system is activated by opioid peptides mainly at the midbrain periaqueductal gray (PAG). Although activation of presynaptic opioid receptors has been reported to inhibit gamma-aminobutyric acid (GABA) release, the exact electrophysiological mechanisms are controversial. To elucidate the mechanisms involved in the opioid modulation of presynaptic GABA release, we isolated single PAG neurons with functionally intact synaptic terminals by a mechanical dissociation in the absence of enzyme.

Activation of protein kinase C antagonizes the opioid inhibition of calcium current in rat spinal dorsal horn neurons.

Spinal dorsal horn (SDH) is one of important regions in both nociceptive transmission and antinociception. Opioid peptides produce analgesia via regulation of neurotransmitter release through modulation of voltage-dependent Ca(2+) channel (VDCC) in neuronal tissues. The modulatory effect of micro-opioid receptor (MOR) activation on VDCC was investigated in acutely isolated rat SDH neurons under the conventional whole-cell patch-clamp recording mode.

Electroacupuncture enhancement of natural killer cell activity suppressed by anterior hypothalamic lesions in rats.

Background/objective: Neuroendocrine hormones are derived from the hypothalamus. The central nervous system, particularly the hypothalamus, is capable of modulating the cytolytic activity of adherent natural killer (NK) cells. In addition, electroacupuncture (EA) stimulation of the Zusanli (ST36) acupoint enhances splenic NK cell and cytokine activities in rats.