Computational Anatomical Analysis of the Basal Forebrain Corticopetal System

Abstract

The basal forebrain (BF) is comprised of a neurochemically heterogeneous population of neurons, including cholinergic, GABA-ergic, peptidergic, and possibly glutamatergic neurons, that project to the cerebral cortex, thalamus, amygdala, posterior hypothalamus and brain stem. This multitude of ascending and descending pathways participate in a similarly bewildering number of functions, including cognition, motivation, emotion, and autonomic regulation. Traditional anatomical methods failed to grasp the basic organizational principles of this brain area and likened it at best to the organization of the brain stem reticular formation. Our studies, using various computational methods for analyzing the spatial distribution and numerical relations of different chemically and hodologically characterized neuronal populations, as well as fully reconstructed electrophysiologically identified single neurons, began to unravel the organizational principles of the BF. According to our model, the different cell types form large-scale cell sheets that are aligned to each other in a specific manner Within each cell system, the neurons display characteristic discontinuous distributions, including high density clusters. As a result of nonhomogeneity within individual cell populations and partial overlapping between different cell types, the space containing the bulk of cholinergic neurons comprises a mosaic of various size cell clusters. The composition, dendritic orientation, and input—output relationships of these high density cell clusters show regional differences. It is proposed that these clusters represent specific sites (modules) where information processed in separate streams can be integrated. Via this BF mechanism a topographically organized prefrontal input could allocate attentional resources to cortical associational areas in a selective self-regulatory fashion.