Activity Regulates Functional Connectivity from the Vomeronasal Organ to the Accessory Olfactory Bulb

Abstract

The mammalian accessory olfactory system is specialized for the detection of chemicals that identify kin and conspecifics. Vomeronasal sensory neurons (VSNs), residing in the vomeronasal organ, project axons to the accessory olfactory bulb (AOB) where they form synapses with principle neurons, known as mitral cells. The organization of this projection is quite precise and is believed to be essential for appropriate function of this system. However, how this precise connectivity is established is unknown. We show here that in mice the vomeronasal duct is open at birth, allowing external chemical stimuli access to sensory neurons, and that these sensory neurons are capable of releasing neurotransmitter to downstream neurons as early as the first post-natal day. Using major histocompatibility complex class I (MHC-1) peptides to activate a selective subset of VSNs during the first few post-natal days of development, we show that increased activity results in exuberant VSN axonal projections and a delay in axonal coalescence into well-defined glomeruli in the AOB. Finally, we show that mitral cell dendritic refinement occurs just after the coalescence of pre-synaptic axons. Such a mechanism may allow the formation of precise connectivity with specific glomeruli that receive input from sensory neurons expressing the same receptor type.

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

“…The coalescence of VSN axons into glomeruli requires expression of a VR and is dependent on activity (Belluscio et al, 1999;Hovis et al, 2012;Rodriguez et al, 1999). It is possible that VR-induced …”

“…Sensory activity can regulate the coalescence and refinement of axons in the AOB (Hovis et al, 2012). The activity-regulated expression of Kirrel2 and Kirrel3 in VSNs may contribute to the control of axonal coalescence in the AOB.…”

Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

“…This morphology indicates that sensory computation in AOB mitral cells is fundamentally different from the processing of "glomerulus-specific" information by their MOB counterparts (Dulac and Torello, 2003). Despite important recent insights into the organizational principles of connectivity, sensory input, and integration in the AOB (Del Punta et al, 2002;Ma and Lowe, 2004;Sugai et al, 2005;Castro et al, 2007;Ben-Shaul et al, 2010;Smith and Araneda, 2010;Hovis et al, 2012;Leszkowicz et al, 2012;Shpak et al, 2012;Tolokh et al, 2013;Hammen et al, 2014), a conceptual understanding of how the biophysical properties of AOB mitral cells affect their computations is lacking.…”

Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons

“…This immunological signature must be interpreted by the olfactory system. It is now well established that, in freely behaving mice, nonvolatile peptides gain access to sensory neurons of both the main olfactory system and the VNO during behavioural situations involving direct physical contact 21,22 , that such peptides are powerful ligands for subsets of vomeronasal and olfactory sensory neurons [21][22][23][24][25] (VSNs and OSNs, respectively), that they induce brain activity downstream from the sensory neurons in vivo 26 , and that synthetic MHC peptide ligands can be discriminated in social preference tests 22 and influence social learning and reproductive function in the context of the Bruce effect test 21 . However, it is important to note that there is also considerable evidence for the use of MHC-independent, individual identity signatures in mice in specific behavioural contexts 27,28 (but see the discussion in Ruff et al 29 ).…”