Distribution, development, pharmacology, and function of cholinergic receptor subtypes in the frog optic tectum.

摘要

The optic tectum is the primary brain center for processing visual signals in non-mammalian vertebrates. The retina connects with the tectum in a point-to-point manner in which specific areas of visual space are represented in particular tectal regions. The establishment of this point-to-point order depends upon neuronal activity (Constantine-Paton, et al., 1990), consequently, understanding what types of receptors are present provides insight into how neurotransmitters influence tectal activity and visual system organization.; Earlier studies have demonstrated that the neurotransmitter acetylcholine modulates tectal excitability (Fite and Wang, 1986; Titmus et al., 1999) and connectivity (Schmidt, 1985, 1995; Tu et al., 2000), but the receptor subtypes that mediate these effects had not been assessed. Using subtype-selective radioligands, I found that at least 4 different acetylcholine receptor subtypes exist in the frog optic tectum (non-alpha7 nicotinic, alpha7-like nicotinic, M1-like muscarinic, and M2-like muscarinic). These receptors are all expressed in the developing tadpole brain as well. Unilateral optic nerve transection indicated that non-alpha7 receptors are primarily located on retinal ganglion cell terminals and alpha7-like receptors are probably located on the afferent terminals from the nucleus isthmi, the major source of cholinergic input to the tectum. Both muscarinic receptor subtypes were associated with tectal dendrites.; To ascertain the function of these receptors and their influence on visual topography, I chronically treated the tectum with non-radiolabeled forms of the subtype-selective drugs and assayed visual map integrity. Blockade of the nicotinic receptors, slightly, but significantly, disrupted the visual map. There was, however, a robust disruption of this map when M1-like muscarinic receptors were blocked. In contrast, the inhibition of M2-like receptor function produced the first reported compression of the map.; My results indicate that multiple acetylcholine receptor subtypes are present and are functional in the frog optic tectum. Non-alpha7 receptors probably serve to enhance glutamate release from retinal ganglion cell terminals, while alpha7-like receptors may increase acetylcholine release in the tectum. M1-like receptors might facilitate the activation of glutamate receptors important for maintaining visual map organization, while M2-like receptors likely limit the excitation of tectal cells produced by other inputs.