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

Abstract

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) interneuron activity 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 lead to reduced odor-evoked Ca2+-responses in glomeruli of the main OB, underscoring the HDB’s role in odor response modulation. Furthermore, selective, light-mediated silencing of only HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Here we provide evidence for a novel tri-synaptic paraventricular nucleus (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.

Top-down acetylcholine contributes to social discrimination via enabling action potentials in olfactory bulb vasopressin cells

“…Intriguingly, it was shown that the blockade of muscarinic neurotransmission in the OB by scopolamine does not impair single-molecule odor recognition 64 . However, non-ACh specific optogenetic silencing of overall release from HDB projections in the OB impairs social habituation to female conspecific mice 30 . In addition, here we demonstrated that the injection of the muscarinic antagonist atropine in the OB efficiently blocks the recognition of a known rat in the social discrimination task.…”

“…Cholinergic neurons in the HDB are the only known source that provides centrifugal neuromodulatory inputs to the GL of the OB, where VPCs are predominantly located 8,29,30 . Following social interaction, the number of pERK + cholinergic HDB neurons was significantly higher compared to rat urine exposure (Fig.…”

“…Reduced GABAergic inhibition by ACh was already observed in hypothalamic VPCs, resulting in increased VP release in-vitro 46,47 . Non ACh-specific optogenetic silencing of all vesicular release from HDB projections in the OB reduces glomerular responses to odor stimulation in-vivo 30 . In addition, optogenetic stimulation of specifically HDB cholinergic projections in the OB in-vivo increases odor responses in projection neurons 37,38 .…”

“…Non ACh-specific silencing of all vesicular release from HDB projections in the OB reduces glomerular activity to odor stimulation in-vivo [34]. In addition, optogenetic specific stimulation of HDB cholinergic projections in the OB in-vivo increases odor responses in projection neurons [41,42].…”

“…If this activating drive of ACh is indeed involved in triggering VPC excitation in behaving rats, we hypothesized that ACh is likely released into the OB during social interaction. In other words, ACh neurons that are known to project to the OB from the horizontal limb of the diagonal band of Broca (HDB) [33,34] should get activated in a social context. Activity of the cholinergic system is correlated with changes in sensations or internal states such as arousal or attention [35][36][37][38][39][40].…”