The diagonal band of broca continually regulates olfactory-mediated behaviors by modulating odor-evoked responses within the olfactory bulb

Sensory perception is modulated in a top-down fashion by higher brain regions to regulate the strength of its own input resulting in the adaptation of behavioral responses. In olfactory perception, the horizontal diagonal band of broca (HDB), embedded in the basal forebrain modulates olfactory information processing by recruiting olfactory bulb (OB) interneurons to shape excitatory OB output. Currently, little is known about how specific HDB to OB top-down signaling affects complex olfactory-mediated behaviors. Here we show that the olfactory bulb is strongly and differentially innervated by HDB projections. HDB-silencing via tetanus toxin light chain led to reduced odor-evoked Ca2+-responses in glomeruli of the OB, underscoring HDBs role in odor response modulation. Furthermore, selective, light-mediated silencing of HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Mono-transsynaptic tracing studies indicated a robust HDB innervation from the paraventricular nucleus (PVN). Here we provide evidence for a novel tri-synaptic PVN-HDB-OB axis responsible for modulating these types of behavior. Thus, HDB to OB projections constitute a central top-down pathway for olfactory-mediated habituation and discrimination behaviors.