Abstract
The olfactory bulb (OB), the first relay for odor processing in the brain, receives dense GABAergic and cholinergic long-range projections from basal forebrain (BF) nuclei that provide information about the internal state and behavioral context of the animal. However, the targets, impact, and dynamic of these afferents are still unclear. How BF synaptic inputs modulate activity in diverse subtypes of periglomerular (PG) interneurons using optogenetic stimulation and loose cell-attached or whole-cell patch-clamp recording in OB slices from adult mice were studied in this article. GABAergic BF inputs potently blocked PG cells firing except in a minority of calretinin-expressing cells in which GABA release elicited spiking. Parallel cholinergic projections excited a previously overlooked PG cell subtype via synaptic activation of M1 muscarinic receptors. Low-frequency stimulation of the cholinergic axons drove persistent firing in these PG cells, thereby increasing tonic inhibition in principal neurons. Taken together, these findings suggest that modality-specific BF inputs can orchestrate synaptic inhibition in OB glomeruli using multiple, potentially independent, inhibitory or excitatory target-specific pathways.
Highlights
Basal forebrain (BF) nuclei innervate many regions of the brain including the entire neocortex, hippocampus, amygdala, thalamus and hypothalamus with diffuse long-range projections releasing GABA, ACh and, more rarely, glutamate
Cholinergic synapses are abundant in the glomerular layer (Hamamoto et al 2017) where muscarinic receptors exert a strong control on intraglomerular inhibition (Liu et al 2015) suggesting that PG cells are another likely target of cholinergic axons
ChR2 fused with eYFP was first targeted to BF cholinergic neurons by injecting a viral construct into the HDB/magnocellular preoptic nucleus (MCPO) of ChatCre mice (Fig.2A)
Summary
Basal forebrain (BF) nuclei innervate many regions of the brain including the entire neocortex, hippocampus, amygdala, thalamus and hypothalamus with diffuse long-range projections releasing GABA, ACh and, more rarely, glutamate. These projections provide cues about the behavioral context and internal state of the animal. They modulate multiple synaptic, cellular and network processes at a variety of temporal and spatial scales thereby regulating sensory perception, metabolic functions such as food intake, brain states and important cognitive functions including attention, arousal, memory or learning (Ballinger et al 2016; Picciotto, Higley, and Mineur 2012). Cholinergic synapses are abundant in the glomerular layer (Hamamoto et al 2017) where muscarinic receptors exert a strong control on intraglomerular inhibition (Liu et al 2015) suggesting that PG cells are another likely target of cholinergic axons
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