Centrifugal cholinergic modulation of the bulbar vasopressin system

The olfactory sense is essential for social communication in both vertebrates and invertebrates. In rats and mice, the discrimination of conspecifics is known to require vasopressinergic neuromodulation in various brain regions, including the olfactory bulb (OB), which hosts an intrinsic population of vasopressin cells (VPCs). However, we observed that olfactory nerve stimulation alone results in net inhibition of VPCs and is thus unlikely to trigger behaviourally relevant vasopressin (VP) release. On the other hand, we could show that VPCs are preferentially activated during social interaction with a conspecific. Indeed, screening for activating mechanisms in vitro revealed that VPCs become excitable by olfactory inputs in the presence of acetylcholine.
We also could show that cholinergic signalling in the OB contributes to VP-dependent social discrimination, and that cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) are also preferentially activated during social interaction.
Based on these findings we hypothesize that during social interactions there is centrifugal gating of a local neuromodulatory system, the intrinsic vasopressin system of the OB, by a global neuromodulator, acetylcholine, originating most likely from the HDB.
The goal of this proposal is to test this hypothesis by revealing the functional details of the underlying mechanisms that are responsible for the observed context-dependent switch in VPC excitability and facilitation of social discrimination behaviour. To do so, we aim to unravel the synaptic circuits involved in cholinergic modulation of bulbar VPCs. Next, we will dissect this multilayered modulatory network in vivo by studying the impact of recurrent cholinergic HDB fibres on bulbar VP release and social discrimination behaviour.