Calretinin-Expressing Neurons in the Basal Forebrain Specifically Contact Granule Cells in the Olfactory Bulb and Modulate Odor Learning.

GABAergic neurons in basal forebrain (BF) nuclei project densely to all layers of the mouse main olfactory bulb (OB), the first relay in odor information processing. However, BF projection neurons are diverse, and the contribution of each subtype to odor information processing is not known. In the present study, we used retrograde and anterograde tracing methods together with whole-brain light-sheet analyses, patch-clamp recordings coupled with optogenetic and chemogenetic approaches during spontaneous odor discrimination, and go/no-go odor discrimination/learning tests to characterize the synaptic targets in the OB of BF calretinin-expressing (CR+) GABAergic cells and to reveal their functional implications. We used mice of either sex to show that OB-projecting CR+ neurons innervate the bulbar granule cell (GC) layer but not the glomerular layer. Optogenetic stimulation of CR+ axonal projections in OB slices elicited monosynaptic GABAergic currents in GCs. Retrograde rabies virus-based transsynaptic tracing experiments confirmed these synaptic connections and further suggested that CR+ neurons provide the principal, if not the unique, BF input onto GCs. Chemogenetic inhibition of CR+ neurons in the BF of male mice did not affect odor discrimination in habituation/dishabituation tasks but led to impairment in odor learning during go/no-go odor-associative tasks. Our results revealed a subtype-specific projection pattern in the OB of a select population of BF neurons and suggested that distinct BF GABAergic projections have distinct effects on odor information processing and learning.