Topographic Mapping between Basal Forebrain Cholinergic Neurons and the Striatum in Rats: An Investigation of Inputs to the Nucleus Basalis

Abstract

The cholinergic neurons of the basal forebrain, which represent the major source of acetylcholine to virtually all cortical regions and layers, underlie fundamental aspects of cognitive function. However, very little is known about how activity in these neurons relates to behavior, as previous experimental approaches have been hindered by challenges associated with the anatomical and morphological complexities of the basal forebrain. Preliminary unpublished data collected in the Witten lab revealed that neural responses within the nucleus basalis differ based on spatial organization: medial recording sites tended to be associated with elevated activity during reward-seeking action and reward delivery, while lateral recording sites tended to be associated with elevated activity during reward consumption. These results motivate my project: characterization of cholinergic inputs to the nucleus basalis. We hypothesize that the observed functional differences between cholinergic cells imply that input structures differentiate between medial and lateral regions. As a means of addressing this, we injected viruses expressing different fluorophores into several striatal structures known to send projections to the nucleus basalis and examined anterograde travel into the region. Tracing results were consistent with a topographic mapping between the striatal origins and the basal forebrain, with the neurons of the dorsal striatum, tail of the striatum, and ventral striatum preferentially innervating dorsal, lateral, and ventral basal forebrain regions, respectively. To our knowledge, these experiments, together with the preliminary unpublished data, are among the first to provide evidence in support of a relationship between spatial organization and functional properties within the basal forebrain cholinergic system.