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Enhanced Excitability (enhanced + excitability)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001
Marco Pistis
Abstract Cannabinoids activate the firing of mesoprefrontocortical dopamine neurons and release dopamine in the prefrontal cortex. This study was undertaken with the aim of clarifying the interaction between cannabinoids and mesocortical system in the prefrontal cortex. The effect of ,9 -tetrahydrocannabinol (,9 -THC) and the synthetic CB1 agonist WIN55,212,2 (WIN) was studied by extracellular single unit recordings, in chloral hydrate anaesthetised rats, on the spontaneous activity of pyramidal neurons and on the inhibition produced on these neurons by the electrical stimulation of the ventral tegmental area (VTA). Intravenously administered ,9 -THC and WIN (1.0 and 0.5 mg/kg, respectively), increased the firing rate of pyramidal neurons projecting to the VTA. VTA stimulation produced a phasic inhibition (167 ± 6 ms) in 79% of prefrontal cortex pyramidal neurons. ,9 -THC and WIN reverted this inhibition in 73% and 100% of the neurons tested, respectively. The subsequent administration of the selective CB1 antagonist SR141716A (1 mg/kg) readily suppressed the effects of both cannabinoids and restored the inhibitory response to VTA stimulation. Moreover, when administered alone, SR141716A prolonged the inhibition in 55.6% of the neurons tested. The results indicate that stimulation of CB1 receptors by cannabinoids results in an enhanced excitability of prefrontal cortex pyramidal neurons as indexed by the suppression of the inhibitory effect of VTA stimulation and by the increase in firing rate of antidromically identified neurons projecting to the VTA. Furthermore, our results support the view that endogenous cannabinoids exert a negative control on dopamine activity in the prefrontal cortex. This study may be relevant in helping to understand the influence of cannabinoids on cognitive processes mediated by the prefrontal cortex. [source]

Electroacupuncture attenuates visceral hyperalgesia and inhibits the enhanced excitability of colon specific sensory neurons in a rat model of irritable bowel syndrome

NEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2009
G.-y. Xu
Abstract, The causes of irritable bowel syndrome remain elusive and there are few effective treatments for pain in this syndrome. Electroacupunture (EA) is used extensively for treatment of various painful conditions including chronic visceral hyperalgesia (CVH). However, mechanism of its analgesic effect remains unknown. This study was designed to investigate effect of EA on colon specific dorsal root ganglion (DRG) neurons in rats with CVH. CVH was induced by intracolonic injection of acetic acid (AA) in 10-day-old rats. Electromyography and patch clamp recordings were performed at age of 8,10 weeks. Colon DRG neurons were labelled by injection of DiI into the colon wall. EA was given at ST36 in both hindlimbs. As adults, neonatal AA-injected rats displayed an increased sensitivity to colorectal distension (CRD) and an enhanced excitability of colon DRG neurons. EA treatment for 40 min significantly attenuated the nociceptive responses to CRD in these rats; this attenuation was reversed by pretreatment with naloxone. EA treatment for 40 min per day for 5 days produced a prolonged analgesic effect and normalized the enhanced excitability of colon DRG neurons. Furthermore, in vitro application of [D-Ala2, N -MePhe4, Gly5 -Ol] enkephalin (DAMGO) suppressed the enhanced excitability of colon neurons from rats with CVH. These findings suggest that EA produced-visceral analgesia, which might be mediated in a large part by endogenous opioids pathways, is associated with reversal of the enhanced excitability of colon DRG neurons in rats with CVH. [source]

Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture

THE JOURNAL OF PHYSIOLOGY, Issue 9 2010
Huaxia Tong
Principal neurons of the medial nucleus of the trapezoid body (MNTB) express a spectrum of voltage-dependent K+ conductances mediated by Kv1,Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9,P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K+]o medium. Whole cell patch-clamp recordings were made after 7,28 days in vitro. MNTB neurons cultured in high-K medium maintained a single AP firing phenotype, while low-K cultures had smaller K+ currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx-free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high-K aCSF only transiently increased spontaneous AP firing (<2 min) and did not measurably increase synaptic activity. Chronic depolarization in high-K cultures raised basal levels of [Ca2+]i, increased Kv3 currents and shortened AP half-widths. These events relied on raised [Ca2+]i, mediated by influx through voltage-gated calcium channels (VGCCs) and release from intracellular stores, causing an increase in cAMP-response element binding protein (CREB) phosphorylation. Block of VGCCs or of CREB function suppressed Kv3 currents, increased AP duration, and reduced Kv3.3 and c- fos expression. Real-time PCR revealed higher Kv3.3 and Kv1.1 mRNA in high-K compared to low-K cultures, although the increased Kv1.1 mRNA was mediated by a CREB-independent mechanism. We conclude that Kv channel expression and hence the intrinsic membrane properties of MNTB neurons are homeostatically regulated by [Ca2+]i -dependent mechanisms and influenced by sustained depolarization of the resting membrane potential. [source]