GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat

Abstract

The extrathalamic relay from the brainstem reticular formation to the cerebral cortex in the basal forebrain has been thought to be constituted predominantly, if not exclusively, by cholinergic neurons. In contrast, the septohippocampal projection has been shown to contain an important contingent of gamma-aminobutyric acid (GABA)ergic neurons. In the present study, we investigated whether GABAergic neurons also contribute to the projection from the basal forebrain to neocortical regions, including the mesocortex (limbic) and the isocortex in the rat. For this purpose, retrograde transport of cholera toxin (CT) was examined from the medial prefrontal cortex for the mesocortex and from the parietal cortex for the isocortex and was combined with dual-immunohistochemical staining for either choline acetyltransferase (ChAT) or glutamic acid decarboxylase (GAD) in adjacent series of sections. Retrogradely labelled GAD+ neurons were codistributed with retrogradely labelled ChAT+ neurons through the basal forebrain from both the prefrontal and the parietal cortex, suggesting parallel, widespread cortical projections. The GAD+ cortically projecting cells were similar in size to the ChAT+ cells, thereby indicating that they comprise a contingent of the magnocellular basal cell complex. The proportions of retrogradely labelled neurons that were GAD+ (approximately one-third) were equal to or greater than those that were ChAT+ from both the prefrontal cortex and the parietal cortex. In addition, the total of GAD+ and ChAT+ neurons did not account for the total number of cortically projecting cells, indicating that another equivalent proportion of chemically unidentified noncholinergic neurons also contributes to the basalocortical projection. Accordingly, as in the allocortex, GABAergic, cholinergic, and other unidentified noncholinergic neurons may have the capacity to modulate activity in the mesocortex (limbic) and the isocortex through parallel, widespread projections.

Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats

“…Some orexin-positive projections to the basal forebrain appear to form synapses onto neurons that were not immunopositive for choline acetyltransferase (Fadel et al 2005). Many of these neurons appear to be magnocellular and parvalbuminimmunoreactive (unpublished data) suggesting that they may contribute to the GABAergic component of the basalocortical projection system (Gritti et al 1993(Gritti et al , 1997Zaborszky et al 1997). In summary, the present experiments provide evidence that orexin-1 receptor blockade can disrupt accuracy in the present attention-demanding task, but clearly, additional work is needed to identify the mechanisms underlying the observed accuracy impairments.…”

Topographic Mapping between Basal Forebrain Cholinergic Neurons and the Medial Prefrontal Cortex in Mice

“…The mice in which injections had produced labeled axons in the medial pathways also showed a strong innervation of superficial layers in IL, PL, and ACv, suggesting that cholinergic fibers arrive via different routes in the superficial and deep layers in the mPFC regions. Previous work has studied the topographic mapping of the cholinergic system using a combination of retrograde tracing with post hoc immunohistochemical identification (Bigl et al, 1982;Price and Stern, 1983;Zaborszky et al, 1986Zaborszky et al, , 1999Gritti et al, 1997Gritti et al, , 2003. Although these studies have provided a wealth of knowledge and have demonstrated a mapping of neurons in the basal forebrain to discrete regions in the cortex, they have mainly focused on the innervation of large cortical areas that were located far apart.…”

Neuroanatomy and neurochemistry of sleep

“…When recorded in head-restrained rats, neurons that were immunohistochemically identified as cholinergic cells discharged in bursts during waking and REMS, and fell silent during NREMS [38]. However, of BF neurons projecting to the cortex more are GABAergic than cholinergic in the rat [39]. Of those projecting to the wake-regulating lateral hypothalamus, half can be considered GABAergic, about 25% glutamatergic and only 10% cholinergic [40].…”