Activity-dependent mapping in the retinotectal projection.

It is now 15 years since the discovery that N-methyl-d-aspartate receptor activity is required to maintain the refined topographic organization of retinotectal projections. Recent studies have identified additional components of the signaling pathways required for activity-dependent map formation and maintenance. Nitric oxide and brain-derived neurotrophic factor, candidate retrograde messengers, and serotonin and acetylcholine, modulators of neuronal excitability, all affect mapping. These studies indicate that the mapping process intersects with other processes fundamental to visual system development and function, such as process outgrowth, synaptic turnover and neuromodulation.

Serotonergic reticular formation cells in Rana pipiens: categorization, development, and tectal projections.

The reticular formation contributes serotonin to many brain regions, including the optic tectum. We examined the organization and development of its serotonergic neurons in the leopard frog. Serotonin-immunoreactive (5-HT-ir) cells in adult frogs were organized into 10 distinct populations that were identified on the basis of their location and cellular morphology. Populations ranged in size from 16 to 2,066 cells and sometimes spanned more than one previously identified nuclear region. Four of the ten populations were absent in tadpoles. The remaining populations, though present, had two contrasting patterns of development. Half of the populations were established early and showed little change in numbers during tadpole stages but increased in size in juvenile and adult frogs. The other half increased dramatically during tadpole stages but failed to add many more cells in juveniles and adults. Three populations provided 90% of the serotonergic projections from the reticular region to the adult optic tectum. These projections were established early in development and likely originated from the dorsal raphe, median raphe, raphe pontis, raphe magnus, and reticularis pontis oralis. Termination sites were located in midtectal layers and were not topographically organized. We conclude that serotonergic cells within the reticular formation of the leopard frog have an organization similar to that found in mammals, that the overall increase in numbers of these cells is attributable to growth in different cell populations at different stages, and that input from this region changes activity levels in the optic tectum in a global rather than a site-specific manner.

Sculpting the visual map: the distribution and function of serotonin-1A and serotonin-1B receptors in the optic tectum of the frog.

Agonists of serotonin (5-HT)-1 receptors modulate the synaptic strength of the connection between retinal ganglion cells and neurons of the frog optic tectum in brain slices (Brain Res. 1998;781:167-181). We have now used autoradiographic receptor binding techniques to determine the location of 5-HT1A and 5-HT1B binding sites in the laminated optic tectum. 5-HT1A binding sites, as labeled with [3H]8-hydroxy-dipropylaminotetralin (8-OH-DPAT), were highest in the superficial, retinorecipient layers of the tectum, intermediate in layers 6 and 7 and low in the remaining layers. Binding densities in all of these layers were unaffected by optic nerve lesion. 5-HT1B binding sites were visualized using [125I]iodocyanopindolol (ICYP). Binding densities were highest in the plexiform layers 5 and 7 and intermediate in layers 6 and 8. Binding sites were present at low levels in layer 9; however, optic nerve lesion resulted in a strong upregulation of these sites in this layer. Pharmacological manipulation of receptor activation resulted in changes in the activity-dependent visual map that is created at the tectum by retinal ganglion cell terminals. Chronic treatment of the tectum with SB-224289, a selective antagonist of 5-HT1B receptors, disrupted the topographic map. In contrast, exposure to WAY-100635, a selective antagonist of 5-HT1A receptors, refined it. We conclude that both 5-HT1A and 5-HT1B receptors are present in the adult frog tectum and that changes in their activation levels can produce changes in retinotectal transmission levels that drive visual plasticity in opposite directions.

Smoking, nicotine and visual plasticity: does what you know, tell you what you can see?

Nicotine exposure alters activity-dependent synaptic plasticity processes. Effects on learning and memory outcomes, and the synaptic changes that underlie them, are well-documented. Parallels in hippocampal and visual system pharmacology suggest that nicotine has the potential to alter activity-dependent structural organization in visual areas. Such alterations may contribute to deficits in visual performance reported in smoking exposed individuals.

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

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.

Bidirectional modulation of visual plasticity by cholinergic receptor subtypes in the frog optic tectum.

Cholinergic input to the optic tectum is necessary for visual map maintenance. To understand why, we examined the effects of activation of the different cholinergic receptor subtypes in tectal brain slices and determined whether the retinotectal map was affected by manipulations of their activity in vivo. Both alpha-bungarotoxin sensitive and insensitive nicotinic receptor agonists increased spontaneous postsynaptic currents (sPSCs) in a subpopulation of patch-clamped tectal cells; application of subtype selective receptor antagonists reduced nicotine-induced increases in sPSCs. Activation of alpha-bungarotoxin insensitive nicotinic receptors also induced substantial inward current in some cells. Muscarinic receptor mediated outward current responses were blocked by the M2-like muscarinic receptor antagonists himbacine or AF-DX 384 and mimicked by application of the M2-like agonist oxotremorine. A less frequently observed muscarinic response involving a change in sPSC frequency appeared to be mediated by M1-like muscarinic receptors. In separate experiments, pharmacological manipulation of cholinergic receptor subtype activation led to changes in the activity-dependent visual map created in the tectum by retinal ganglion cell terminals. Chronic exposure of the tectum to either alpha-bungarotoxin insensitive, alpha-bungarotoxin sensitive or M1-like receptor antagonists resulted in map disruption. However, treatment with the M2-like receptor antagonist, AF-DX 384, compressed the map. We conclude that nicotinic or M1-like muscarinic receptors control input to tectal cells while alpha-bungarotoxin insensitive nicotinic receptors and M2-like muscarinic receptors change tectal cell responses to that input. Blockade of the different cholinergic receptor subtypes can have opposing effects on map topography that are consistent with expected effects on tectal cell activity levels.