Nicotine exposure refines visual map topography through an NMDA receptor‐mediated pathway

Abstract

The precise mapping of one surface onto another is fundamental to visual system organization and depends upon adequate stimulation of postsynaptic targets to stabilize correctly placed synapses. As exogenous nicotine alters neuronal activity, we investigated whether it would affect the visual map created by retinal ganglion cell terminals in the frog optic tectum. Chronic exposure of the tectum to nicotine decreased the retinal area from which cells project to a given tectal site. This map refinement was also produced by exposure to either the alpha-bungarotoxin sensitive nicotinic receptor agonist, anatoxin-a or the alpha-bungarotoxin-insensitive nicotinic receptor agonist epiboxidine. Immunocytochemical studies using mAb306 and mAb22 demonstrated that alpha-bungarotoxin-sensitive and -insensitive nicotinic receptors, respectively, occupied different tectal sites. Choline acetyltransferase immunoreactivity overlapped with mAb306, but not mAb22, staining. The developing optic tectum was more sensitive to nicotine than the adult tectum and nicotine induced both map refinements and map disruptions in a concentration-dependent manner. Blockade of the N-methyl-D-aspartate (NMDA) receptor with D(-)-2-amino-5-phosphonopentanoic acid (D-APV) prevented nicotine from refining the map in the adult tectum. Exposure to the use-dependent NMDA antagonist MK801 alone had no effect on retinotectal topography but in combination with either NMDA or nicotine it disrupted the map. Exposure to NMDA alone produced refinement. We conclude that the map refinement induced by chronic nicotine treatment has as its basis an increase in the level of NMDA receptor activity. The data are consistent with a model whereby map topography can be bidirectionally affected by either increasing or decreasing NMDA receptor activity.

Spatial and intracellular relationships between the α7 nicotinic acetylcholine receptor and the vesicular acetylcholine transporter in the prefrontal cortex of rat and mouse

“…This conclusion is further strengthened by the facts that this antibody recognizes an α7nAChR immunoreactive band of increasing density over time in primary cultures of rat hippocampal neurons (Arnaiz-Cot et al , 2008). In addition, the α7nAChR antibody used in our study has been shown to produce a similar pattern of labeling to α-bungarotoxin in the frog optic tectum (Yan et al, 2006) and the α7nAChR mRNA distribution and ligand binding in the rat central nervous system (Dominguez del Toro et al, 1994, Gotti and Clementi, 2004, Gotti et al, 2006). …”

Isthmotectal axons maintain normal arbor size but fail to support normal branch numbers in dark‐reared Xenopus laevis

“…Another intriguing possibility is raised by a recent report indicating that isthmic axons themselves are likely to have nicotinic presynaptic receptors (Yan,2006). Therefore, a positive feedback situation may arise once an isthmotectal axon forms a cluster of branches.…”

The instructive role of binocular vision in the Xenopus tectum

“…Each point of acetylcholine (ACh) release could potentially influence multiple retinotectal axons, and one can envision a situation in the which several isthmotectal branches or axons would have synergistic effects if they fired in a correlated manner in a localized tectal volume; the combined ACh generated by multiple nearby sources could easily have qualitatively different effects from the ACh generated by a single, isolated branch. This possibility is particularly likely in light of recent observations that isthmotectal axons themselves have acetylcholine receptors (Yan et al 2006). A cluster of isthmotectal axons with correlated activity might therefore create such a large pool of ACh that their terminals in turn would release additional ACh, in turn adding to the effect on the ACh receptors on the retinotectal terminals.…”