Neuroanatomical Analysis of a Direct Optic Pathway to the Brainstem

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

An expanding research and clinical literature indicates that a strong association exists between light stimulation and a variety of affective, behavioral, and cognitive functions. At present, little is known about the neural circuitry whereby environmental light stimulation may influence the serotonin system, one of the oldest and most widespread neurochemical systems in the brain. Recently, the existence of a direct retinalpathway to the large, serotonergic dorsal raphe nucleus (DRN) of the brainstem has been described in a number of different vertebrate species. The DRN has widespread projections to the forebrain and contains the greatest proportion of serotonergic neurons in the brainstem. Several neuroanatomical studies conduct by the PI indicate that the retinal-DRN project is substantially large in diurnal than in nocturnal species. At present, the functional correlates of this direct optic pathway to the DRN are unknown. Several exploratory studies are proposed to investigate the functional correlates of optic input to the DRN and serotonergic system using Mongolian gerbils, a highly visual diurnal rodent with a well-developed retinal-DRN projection. Major research objectives include the following: (1) Experiments utilizing the 2-deoxyglucose (2-DG) metabolic technique should reveal whether visual stimulation alters 2-DG uptake in the DRN, and if so, where the greatest uptake occurs. Several kinds of visual stimulation will be presented: (a) exposure to a sustained, high-intensity stimulus, (b) exposure to a flashing light presented at different flash frequencies, (c) exposure to a large-field, random-dot moving pattern presented at different velocities. Experimental animals will be compared with controls exposed only to dim illumination. The effects of electrical stimulation of the optic nerve on 2-DG uptake in the DRN also will be investigated. (2) A second set of experiments will involve application of 5-HT microdialysis techniques in the gerbil DRN to determine whether extracellular 5-HT varies in the DRN over the 24-hour, light:dark cycle. In addition, experiments will be conducted to determine whether a 30-minute presentation of high intensity light stimulation presented at different times of the 24-hour light:dark cycle will alter baseline, extracellular 5-HT levels, particularly in regions of the DRN where optic terminal occur with highest density. These studies should contribute substantially advances in fundamental knowledge about this direct optic pathway to the serotonin system and facilitate a variety of future experiments to determine the effects of DRN stimulation on efferent target structure such as the intergeniculate leaflet, superior colliculus, and visual cortex, all of which receive serotonergic projections from DRN.