Encoding Pheromonal Signals in the Accessory Olfactory Bulb of Behaving Mice

“, its neurons respond to molecules other than pheromones, but it remains to be established whether these molecules are physiologically relevant stimul”

“How is pheromonal information encoded in the mitral cells? Using an array of electrodes implanted in the mouse AOB, Luo and colleagues recently recorded mitral cell activity in freely moving mic”

“…initial investigation of a conspecific and is maintained for a short period of time after the conspecific has been removed (Hashikawa et al., 2016; Luo et al., 2003), suggesting that activity in the AOB changes with duration of investigation, and is not strictly correlated with the presence of…”

“Certain pheromones have been found to activate neurons in the main olfactory system, and the activity of this system has been found necessary for several sexual and social behaviors that likely depend on pheromones (Lin et al., 2004; Luo et al., 2003; Mandiyan et al., 2005; Spehr et al., 2006; Wang et al., 2006; Xu et…”

“In vivo , such molecules probably gain access to the VNO after direct contact with the stimulus source, which is consistent with increases in neuronal activity in the AOB after direct contact with an anaesthetized conspecifi”

“access depends on a vascular pumping mechanism that appears to be activated when animals make nasal contact with a novel stimulus.((52,53)) This system plays a key role in the”

“In conjunction with intracellular recordings from neurons in awake [120,121] and freely moving animals [122], these new approaches will help us to determine when and how dendrites, and their compartments, contribute to the brain’s remarkable capacities for perception, action and memory.”

“More recent studies using genetic tools, electrophysiological recordings, and calcium imaging assays have confirmed this function (Chamero et al., 2007; Holy et al., 2000; Leinders-Zufall et al., 2000; Leypold et al., 2002; Luo et al., 2003; Stowers et al., 2002).”

“The involatile protein darcin is most likely to be detected through the accessory olfactory subsystem which detects scents that are actively pumped to the vomeronasal organ on nasal contact with the scent source [58,59].”

“This organization suggests that an important transformation of sensory information occurs in the AOB, from a segregated sampling system in the VNO to more integrated codes in the AOB (Luo et al., 2003; Meeks et al., 2010).”

“Furthermore, various volatile urinary pheromones activate the MOE with high affinity (2, 24), and some of these likely activate ORs (25).”

“Indeed, sensory neurons in the VNO access mainly nonvolatile stimuli by active pumping of the organ during nasal contact with odorant sources (Wysocki, 1979), and activation of neurons from the AOB requires the nose of the subject to be in direct contact with the snout, face, or anogenital regions of the stimulus anim…”

“…contrast to the apparent specificity of VNO responses for distinct animal cues, a large proportion of output neurons in the AOB, the primary targets of VNO sensory projections, were shown to respond to multiple classes of stimuli (Luo et al., 2003; Hendrickson et al., 2008; Ben-Shaul et al., 2010).”

“Katz’s group [27] has recently performed the first recordings from AOB mitral cells of freely behaving mice, during the investigation of anaesthetized stimulus animals.”

“In particular, consistent with some previous reports (Luo et al., 2003), we find little evidence for widespread activation of VSNs by volatiles, for either “conventional odorants” or ones that were identified from natural sources.”

“Recognition also required scent contact, consistent with detection of involatile components through the vomeronasal system [6, 18].”

“Although it has been claimed (Trinh and Storm, 2003) that volatile constituents of urine may directly activate VNO sensory neurons, AOB mitral cells were only activated when male mice came into direct physical contact with the head or anogenital regions of conspecifics, and exposure to volatile urinary odors failed to…”

“Complex odors such as mouse urine and maternal odors, containing both common odors and pheromones, activate the mouse MOB, as shown by electrical recording of mitral cells (Luo et al., 2003) and c-fos mapping in the glomerular layer (Kelliher et al., 1998; Chang et al., 2001; Schaefer et al., 2002).”

“Recent studies in mice indicate that the vomeronasal organ and the AOB are important in sex and strain discrimination (Stowers et al., 2002; Luo et al., 2003).”

“AOBneurons can reliably detect conspecific sex from urinary cues (9) and strain information from as yet unidentified cues (10).”

“have demonstrated using electrophysiological recordings of mitral cells in the AOB in behaving animals that these cells are only activated when mice make direct physical contact with the odorant source (either the face or anogential regions of an anaesthetised stimulus female [66]).”

“Another example was presented by Luo et al. [ 66 ], who found that neurons in the accessory olfactory bulb are active while mice sniff the mouth region of anesthetized conspecifics.”

“Miniature motorized microdrives (Fee and Leonardo, 2001) containing three independently movable microelectrodes were chronically implanted on 12- to 24-week-old female C57BL/6 mice as described previously (Luo et al., 2003).”

“Previous studies have shown that direct contact with non-volatile odours is needed to activate the VNO (Wysocki et al., 1980; Halpern & Martinez-Marcos, 2003; Luo et al., 2003).”

“Extracellular recordings from AOB mitral cells in behaving mice (Luo et al., 2003) have shown extremely specific responses to natural stimuli with spikes induced by only one out of six mouse odors originating from various strains and genders.”

“A motorized commutator controlled the turning of the recording cable to minimize moving-related torque (Luo et al., 2003).”

“…components of various body odorants such as skin secretions, urine, or scent marks (Wysocki et al., 1980; Halpern and Martinez-Marcos, 2003; Luo et al., 2003), detects primarily pheromones or pheromonal blends which have been shown to play a critical role in mediating neuroendocrine…”

“Thus, physical investigation between mice involving the face and neck areas is shown more frequently and for longer periods of time than to the anogenital area in short-term observations (Luo et al., 2003).”

“AOB mitral neurons, which are postsynaptic to VNO neurons, also show complex responses to the two sexes (Luo et al., 2003), suggesting significant transformation of sex recognition signals downstream of the VNO.”

“AOB mitral cells respond differentially to stimuli from conspecific individuals according to gender and strain (Luo et al., 2003), presumably reflecting stimulation by different chemicals, of vomeronasal sensory neurons expressing different VR receptors (Del Punta et al., 2002).”

“[89] Luo M, Fee MS, Katz LC.”

“Because activation of AOS typically requires direct nasal contact with sources of pheromones (Wysocki et al., 1980; Luo et al., 2003), increased VMHvl activity in response to male stimuli at a distance is likely attributable to MOS input, whereas AOS input may increase VMHvl activity during close…”

“Recent technological advances make it possible to record neural activity in freely moving and vocalizing animals (Yu and Margoliash 1996; Dave et al. 1998; Fee and Leonardo 2001; Hahnloser et al. 2002; Luo et al. 2003; Leonardo and Fee 2005).”

“, 2004); whereas the vomeronasal system detects mainly (Luo et al., 2003), but not exclusively, pheromones (Restrepo et al.”

“This may be related to distinct and complementary factors such as defined gender responses to sex-specific initial signals (Holy et al., 2000; Luo et al., 2003; Ben-Shaul et al., 2010; Haga et al., 2010) probably secondary to modulation by steroid hormones (Leypold et al.”

“In general, the MOE senses generic odorants while the VNE is specialized to detect pheromones and similar heterospecific cues (although there is evidence for significant crosstalk between these systems and a few exceptions to the rule [59]).”

“Novelty and nasal contact stimulate the pumping mechanism required to deliver involatile scent components to the vomeronasal organ (Meredith 1994; Luo et al. 2003).”

“Semiochemical detection by physically isolated sensory neurons in the VNO generally requires animals to make contact with and draw in external stimulus fluids, such as urine and other bodily secretions, which are rich in semiochemical cues [18,19,20,21].”

“Studies in rodents demonstrate that input from accessory olfactory bulb and vomeronasal systems increase neuronal firing when males are exposed to females (Luo et al., 2003).”

“Reconciling this with our results and those of Luo et al. (2003) is possible by assuming that VNO neurons are sensitive to some urine-borne volatiles through very specific receptors (Boschat et al., 2002), but during exploratory behaviour either these volatiles need a carrier protein to reach…”

“This suggests that the vomeronasal organ accesses nonvolatile information concerning sex and genetic identity through active pumping during close contact investigation of the scent source (Luo et al. 2003).”

“The accessory olfactory system is used to detect non-volatile odorants that influence reproductive and aggressive behaviors [105], and also to aid in recognition of conspecifics [122].”

“Results AOB neurons respond to synthetic sulfated steroids There have only been a few studies of the sensory responses of mammalian AOB neuron”

“Unlike the OR cells in the SO (Ma et al., 2003; Tian and Ma, 2004) the OR cells in the VNO do not express the typical transduction elements of the MOE cells, such as adenylate cyclase type III (ACIII) and Golf.”

“Activation of the vomeronasal system by semiochemicals has been demonstrated in electrophysiological studies in awake animals [61] which show that physical investigation of conspecifics”

“Also, the VNO and accessory olfactory system are known to initiate reproductive responses in vertebrates (Halpern & Martı́nez-Marcos 2003; Luo et al. 2003).”

“…have revealed the chemical nature of many of these cues [3–10,11 • ,12,13], the identities of the putative cognate receptors [5,11 • ,14 •• ,15 •• ,16 • ,17 • ,18 •• ], and in some cases, the neural pathways that relay pheromone-evoked sensory neuron activation to the brain [19–22,23 •• ,24].”

“Its ‘‘functionality’’ will be discussed in light of the current opinion on what might be pheromones, that is, so‐called nonvolatile (Luo et al., 2003) or volatile (Leinders‐Zufall et al.”

“Sensory information from the VNO is conveyed through direct projections to the accessory olfactory bulb (38), in which cells were shown to respond strongly to physical contact with conspecifics (39).”

“For example, olfaction plays a large role in the social behaviour of rodents, therefore it is possible that genetic or pharmacological manipulations that alter social behaviours do so via disrupted olfactory processing rather than changes in cognitive pathways common to patients [58].”

“For one, rodents rely on olfaction as their primary sensory system and depend on olfactory cues for the majority of survival-related behaviors (Brennan and Keverne, 1997; Luo et al., 2003; Restrepo et al., 2004).”

“Electrophysiological evidence (Luo et al., 2003) suggests that mice must have direct nasal contact with a conspecifics’ nonvolatile body odours to activate AOB mitral cells in response to VNO signaling.”

“, 2001) evidence that the VNO is able to detect volatile odours, in vivo electrophysiological evidence suggests that activation of putative AOB mitral cells required direct nasal contact with nonvolatile pheromonal stimuli (Luo et al., 2003).”

“To compare the responsivity of the cells in our data set with those reported previously from awake behaving animals (Luo et al., 2003), we calculated for each unit and for each 1:100 dilution stimulus to which it was exposed (MMU and/or FMU) a response index representing the number of excess spikes…”

“In the mouse, intense investigation has revealed VNO sensory neurons that are tuned to either male or female cues [12,13,14 ,27].”

“In this respect, it has been shown in several rodents that the VNO detects under physiological conditions nonvolatile substances (Wysocki et al. 1980; Luo et al. 2003; Moncho-Bogani et al. 2005).”