Abstract
Basal forebrain modulation of central circuits is associated with active sensation, attention, and learning. While cholinergic modulations have been studied extensively the effect of non-cholinergic basal forebrain subpopulations on sensory processing remains largely unclear. Here, we directly compare optogenetic manipulation effects of two major basal forebrain subpopulations on principal neuron activity in an early sensory processing area, i.e. mitral/tufted cells (MTCs) in the olfactory bulb. In contrast to cholinergic projections, which consistently increased MTC firing, activation of GABAergic fibers from basal forebrain to the olfactory bulb leads to differential modulation effects: while spontaneous MTC activity is mainly inhibited, odor-evoked firing is predominantly enhanced. Moreover, sniff-triggered averages revealed an enhancement of maximal sniff evoked firing amplitude and an inhibition of firing rates outside the maximal sniff phase. These findings demonstrate that GABAergic neuromodulation affects MTC firing in a bimodal, sensory-input dependent way, suggesting that GABAergic basal forebrain modulation could be an important factor in attention mediated filtering of sensory information to the brain.
Highlights
The basal forebrain (BF) is a complex of subcortical nuclei with projections to various brain areas and has been implicated in attention and cognitive control
Though we cannot completely exclude that the 7.9% of cells co-labeled with vesicular acetylcholine transporter (VAChT) could be, partially or completely, bulbopetal neurons, we took this finding as a basis for a differential functional analysis of GABAergic and cholinergic projections in the olfactory bulb (OB)
Recording from olfactory bulb output neurons, we show that, in contrast to a local and specific activation of cholinergic fibers, that add an excitatory bias to mitral/tufted cell firing, a selective activation of GABAergic BF fibers leads to bimodal, sensory www.nature.com/scientificreports input dependent effect on OB output: whereas optogenetic stimulation mainly inhibited spontaneous mitral/tufted cells (MTCs) firing, odor-evoked MTC cell spiking was predominantly enhanced; an effect that could be observed on a single neuron level
Summary
The basal forebrain (BF) is a complex of subcortical nuclei with projections to various brain areas and has been implicated in attention and cognitive control. Effects of GABAergic BF axon stimulation in the OB on the other hand were sensory input strength dependent and mainly caused suppression of spontaneous MTC activity while predominantly enhancing odor-evoked MTC spiking. These results suggest that both, cholinergic and GABAergic projections from the same area, rapidly modulate sensory output but might have markedly different impacts on sensory information processing
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