Nervous system

About: Nervous system is a research topic. Over the lifetime, 16729 publications have been published within this topic receiving 847181 citations.

Serotonin modulates the response of embryonic thalamocortical axons to netrin-1.

Abstract: Modifying serotonin (5-HT) abundance in the embryonic mouse brain disrupts the precision of sensory maps formed by thalamocortical axons (TCAs), suggesting that 5-HT influences their growth. We investigated the mechanism by which 5-HT influences TCAs during development. 5-HT1B and 5-HT1D receptor expression in the fetal forebrain overlaps with that of the axon guidance receptors DCC and Unc5c. In coculture assays, axons originating from anterior and posterior halves of the embryonic day 14.5 dorsal thalamus responded differently to netrin-1, reflecting the patterns of DCC and Unc5c expression. 5-HT converts the attraction exerted by netrin-1 on posterior TCAs to repulsion. Pharmacological manipulation of 5-HT1B/1D receptors and intracellular cAMP showed the signaling cascade through which this modulation occurs. An in vivo correlate of altered TCA pathfinding was obtained by transient manipulation of 5-HT1B/1D receptor expression abundance in the dorsal thalamus by in utero electroporation. These data demonstrate that serotonergic signaling has a previously unrecognized role in the modulation of axonal responsiveness to a classic guidance cue.

Gamma Interferon Expression during Acute and Latent Nervous System Infection by Herpes Simplex Virus Type 1

Abstract: This study was initiated to evaluate a role for gamma interferon (IFN-gamma) in herpes simplex virus type 1 (HSV-1) infection. At the acute stage of infection in mice, HSV-1 replication in trigeminal ganglia and brain stem tissue was modestly but consistently enhanced in mice from which IFN-gamma was by ablated monoclonal antibody treatment and in mice genetically lacking the IFN-gamma receptor (Rgko mice). As determined by reverse transcriptase PCR, IFN-gamma and tumor necrosis factor alpha transcripts were present in trigeminal ganglia during both acute and latent HSV-1 infection. CD4+ and CD8+ T cells were detected initially in trigeminal ganglia at day 5 after HSV-1 inoculation, and these cells persisted for 6 months into latency. The T cells were focused around morphologically normal neurons that showed no signs of active infection, but many of which expressed HSV-1 latency-associated transcripts. Secreted IFN-gamma was present up to 6 months into latency in areas of the T-cell infiltration. By 9 months into latency, both the T-cell infiltrate and IFN-gamma expression had cleared, although there remained a slight increase in macrophage levels in trigeminal ganglia. In HSV-1-infected brain stem tissue, T cells and IFN-gamma expression were present at 1 month but were gone by 6 months after infection. Our hypothesis is that the persistence of T cells and the sustained IFN-gamma expression occur in response to an HSV-1 antigen(s) in the nervous system. This hypothesis is consistent with a new model of HSV-1 latency which suggests that limited HSV-1 antigen expression occurs during latency (M. Kosz-Vnenchak, J. Jacobson, D.M. Coen, and D.M. Knipe, J. Virol. 67:5383-5393, 1993). We speculate that prolonged secretion of IFN-gamma during latency may modulate a reactivated HSV-1 infection.

Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system

Abstract: Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechanoreceptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch–clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2–3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system.