Glutamatergic projection neurons in the basal forebrain underlie learned olfactory associational valence assignments

Sensory perception is shaped by experience, giving stimuli behavioral significance. Basal forebrain (BF) cholinergic neurons in mice, which are crucial for arousal and motivation, also regulate sensory processing. Within BF nuclei, glutamatergic (vGlut2BF) neurons receive cholinergic input and modulate behaviors, but their roles in encoding sensory significance remain unclear. Using in vivo calcium imaging, we found that vGlut2BF neurons initially poorly encoded odor identity. However, their response to conditioned odors increased following associative learning, and their population activity more distinctly encoded paired stimuli, reflecting emergent value representation. Furthermore, pairing stimulation or inhibition of vGlut2BF neurons with specific odors altered odor preferences, suggesting that appropriately timed vGlut2BF neuronal activity is sufficient to influence valence assignment. Our findings reveal that vGlut2BF neurons transform sensory input into motivationally significant stimuli, positioning the BF as a key hub for linking sensory processing with motivational states and experience-driven plasticity. Neural mechanisms underlying motivation-driven behaviors are not fully understood. Here authors show that non-cholinergic neurons in rodent basal forebrain link sensory stimuli with motivational states and experience-driven plasticity.