Abstract
Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas.
Highlights
The study of the distribution and percentages of these neurons showed that 34 ± 1.1% of the neurons located in the VDB/HDB were labeled by both fluorescent tracers, while most of the VDB/HDB neurons (44.2 ± 7.4%) were single-labeled by FlGo injected into S1 cortex; only 21.8 ± 2.4% of neurons were labeled by Fast Blue (FB) injected into A1 cortex (Figure 4A)
The immunochemical study revealed that fluorescent labeled neurons appeared to be scattered among the characteristic cholinergic neurons of the different basal forebrain (BF) nuclei and some of them were positive for choline-acetyl transferase promoter (ChAT) immunocytochemistry (Figure 2F)
Simultaneously activating all cortical areas, or as a set of distinct neuronal groups that differentially activate specific cortical regions. Our results support the latter possibility because they reveal that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups
Summary
Acetylcholine (ACh) is essential to normal central nervous system (CNS) function, modulating the activity of the thalamocortical network in many important brain functions, such as arousal (e.g., Buzsáki et al, 1988; Détári, 2000; Szymusiak et al, 2000; Lee et al, 2004; Goard and Dan, 2009), attention (Chiba et al, 1999; Sarter et al, 2003), learning (Wilson and Rolls, 1990a,b; Mayse et al, 2015) and memory (Pauli and O’Reilly, 2008; Hasselmo and Sarter, 2011; Luchicchi et al, 2014; Sarter et al, 2014). It has been proposed that sensory information arrives at the BF through cortico-cortical projections from primary cortical sensory areas via the prefrontal cortex (Zaborszky et al, 1997) Results from both electrophysiological recordings (Golmayo et al, 2003) and inactivation of the prefrontal cortex (Rasmusson et al, 2007) have demonstrated that the prefrontal cortex is necessary for sensory-evoked cortical ACh release. These results strongly support the proposed specific pathway –sensory cortex to prefrontal cortex to BF– for each sensory modality. Our studies suggest that cholinergic projections to the cortex are organized into segregated and overlapping pools of neurons that may modulate specific cortical areas
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