Selectivity of neuromodulatory projections
Dissecting structural connections of neural circuits is the first step towards understanding functional roles of the complex human brain. Researchers at KAIST recently found that the mammalian brain develops neuromodulatory inputs to the cortex in two distinct regimes. Basal forebrain (BF) cholinergic neurons show selective inputs to the single sensory cortex, whereas locus coeruleus (LC) noradrenergic neurons show diverging inputs to multiple sensory areas. Consistent with this anatomical observation, we found that optogenetic activation of cholinergic BF and noradrenergic LC neurons induce selective and global desynchronization of sensory cortices. This is the first discovery of the clear difference of projection patterns from cholinergic BF and noradrenergic LC neurons into primary sensory cortices. These results were published recently in the Journal of Neuroscience (http://www.jneurosci.org/content/36/19/5314.short?rss=1).
The basal forebrain (BF) and locus coeruleus (LC) are major neuromodulatory centers composed of cholinergic and noradrenergic neurons. The BF and LC areas are well-known to project into sensory cortices and modulate sensory processing. It is still unclear, however, how selective their projections are in the sensory cortex. In order to identify projection features from neuromodulatory centers into different sensory cortices, we performed anatomical and functional tracings using retrograde tracers called retrobeads and in vivo electrophysiological experiments.
First, we injected both red and green retrobeads into different primary sensory cortices of mouse brain and traced their labeling in the BF and LC. Cholinergic BF neurons tend to project selectively into specific modalities of the sensory cortex. In addition, they show a clear distinction in their topographic organization within the BF. However, noradrenergic neurons in the LC show diverging projections to multiple cortical areas; the bead-labeled neurons are densely intermingled within the LC.
Next, we measured local field potential (LFP) in the primary sensory cortices while activating BF cholinergic and LC noradrenergic neurons. Consistent with the tracing results, optogenetic activation of cholinergic neurons induces modality-selective LFP desynchronization in each sensory cortex, whereas activation of noradrenergic neurons induces global LFP desynchronization in multiple sensory cortices.
Using a dual retrobead tracing technique, along with optogenetic stimulation, we have identified anatomic and functional differences in the way cholinergic BF neurons and noradrenergic LC neurons project into primary sensory cortices. While BF projections are highly selective to individual sensory cortices, LC projections diverge into multiple sensory cortices. To the best of our knowledge, this is the first definitive proof that BF and LC projections to primary sensory cortices show both anatomic and functional differences in selectivity for modulating cortical activity.
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