Journal of neurophysiology
-
Sphingosine-1-phosphate (S1P) is released by immune cells and is thought to play a key role in chemotaxis and the onset of the inflammatory response. The question remains whether this lipid mediator also contributes to the enhanced sensitivity of nociceptive neurons that is associated with inflammation. Therefore we examined whether S1P alters the excitability of small diameter, capsaicin-sensitive sensory neurons by measuring action potential (AP) firing and two of the membrane currents critical in regulating the properties of the AP. ⋯ In contrast, internal perfusion with GDP-beta-S and S1P increased the number of APs evoked by the current ramp. These results and our finding that the mRNAs for S1PRs are expressed in both the intact dorsal root ganglion and cultures of adult sensory neurons supports the notion that S1P acts on S1PRs linked to G proteins. Together these findings demonstrate that S1P can regulate the excitability of small diameter sensory neurons by acting as an external paracrine-type ligand through activation of G-protein-coupled receptors and thus may contribute to the hypersensitivity during inflammation.
-
We have previously shown that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incerto-thalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that the cholinergic reticular activating system, implicated in regulating states of arousal, modulates ZI activity. ⋯ We also found that carbachol application to an in vitro slice preparation suppresses spontaneous firing of neurons in the ventral sector of ZI (ZIv). Finally, we demonstrate that the majority of ZIv neurons contain parvalbumin and project to POm. Based on these results, we present the state-dependent gating hypothesis, which states that differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby regulating the response properties of higher-order nuclei such as POm.
-
Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This "central hypersensitivity, " which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying "centralization," sciatic nerves of 20-day-old rats were subjected to 13-25 days of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). ⋯ By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons, whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.
-
Cathodal galvanic currents activate primary vestibular afferents, whereas anodal currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to determine the latency and initiation of the human vestibuloocular reflex. Three-dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal subjects. ⋯ At 10-mA stimulation, the g-VOR [x, y, z] on the cathodal side was [0.77 +/- 0.10, -0.05 +/- 0.05, -0.18 +/- 0.06 degrees ] (mean +/- 95% confidence intervals) and on the anodal side was [0.79 +/- 0.10, 0.16 +/- 0.05, -0.19 +/- 0.06 degrees ], with a vertical divergence of 0.20 degrees. Although the horizontal g-VOR could have arisen from activation of the horizontal semicircular canal afferents, the vertical-torsional g-VOR resembled the vestibuloocular reflex in response to roll-plane head rotation about an Earth-horizontal axis and might be a result of both vertical semicircular canal and otolith afferent activations. Pulsed GVS is a promising technique to investigate latency and initiation of the human vestibuloocular reflex because it does not require a large mechanical apparatus nor does it pose problems of head inertia or slippage.
-
Comparative Study
Stimulus for rapid ocular dominance plasticity in visual cortex.
Although it has been known for decades that monocular deprivation shifts ocular dominance in kitten striate cortex, uncertainty persists about the adequate stimulus for deprivation-induced losses of cortical responsiveness. In the current study we compared the effects of 2 days of lid closure and 2 days of monocular blur using an overcorrecting contact lens. ⋯ The quality rather than the quantity of retinal illumination is the key factor for ocular dominance plasticity. These data have implications for both the mechanism and treatment of amblyopia.