Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb

doi:10.1016/j.neulet.2007.12.070

Neuroscience Letters

Volume 438, Issue 2, 20 June 2008, Pages 133-137

https://doi.org/10.1016/j.neulet.2007.12.070 Get rights and content

Abstract

When female mice are mated, they form a memory to the pheromonal signal of their male partner. Several lines of evidence indicate that the neural changes underlying this memory occur in the accessory olfactory bulb (AOB) at the first stage of the vomeronasal system. The formation of this memory depends on the mating-induced release of noradrenaline in the AOB. In addition to noradrenaline, the neuropeptide oxytocin (OT) is also released within the central nervous system during mating. Because OT has been implicated in social memory and its receptors are expressed in the AOB, we hypothesized that OT might promote the strength of synaptic transmission from mitral to granule cells in the AOB. To test this hypothesis, we analyzed the lateral olfactory tract-evoked field potential that represents the granule cell response to mitral cell activation and its plasticity in parasagittal slices of the AOB. Of the 10-, 20-, 50-, and 100-Hz stimulations tested, the 100-Hz stimulation was optimal for inducing long-term potentiation (LTP). OT paired with 100-Hz stimulation that only produced short-term potentiation enhanced LTP induction in a dose-dependent manner. OT-paired LTP was blocked by both the selective OT antagonist desGly-NH₂,d(CH₂)₅[Tyr(Me)²,Thr⁴]-ornithine vasotocin and the N-methyl-d-aspartate (NMDA) receptor antagonist dl-2-amino-5-phosphonovaleric acid. These results indicate that OT can function as a gate to modulate the establishment of NMDA receptor-dependent LTP at the mitral-to-granule cell synapse in the AOB.

Section snippets

Acknowledgements

We thank Dr M. Manning for the gift of desGly-NH₂,d(CH₂)₅[Tyr(Me)²,Thr⁴]-ornithine vasotocin. L.-Y. F. received a Japanese Government Scholarship. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and from Kochi University.

References (46)

P. Brennan
The nose knows who's who: chemosensory individuality and mate recognition in mice
Horm. Behav.
(2004)
P. Brennan et al.
The expression of the immediate-early genes c-fos, egr-1 and c-jun in the accessory olfactory bulb during the formation of an olfactory memory in mice
Neuroscience
(1992)
P. Brennan et al.
Neurotransmitter release in the accessory olfactory bulb during and after the formation of an olfactory memory in mice
Neuroscience
(1995)
P. Brennan et al.
Neural mechanisms of mammalian olfactory learning
Prog. Neurobiol.
(1997)
D. De Wied et al.
Central nervous system effects of the neurohypophyseal hormones and related peptides
Front. Neuroendocrinol.
(1993)
B. Gould et al.
Mapping oxytocin receptor gene expression in the mouse brain and mammary gland using an oxytocin receptor-LacZ reporter mouse
Neuroscience
(2003)
H. Kaba et al.
The effect of microinfusions of drugs into the accessory olfactory bulb on the olfactory block to pregnancy
Neuroscience
(1988)
H. Kaba et al.
Neural basis of olfactory memory in the context of pregnancy block
Neuroscience
(1989)
H. Kaba et al.
Hormonal enhancement of neurogenesis and its relationship to the duration of olfactory memory
Neuroscience
(1988)
K. Kendrick et al.
Neural control of maternal behaviour and olfactory recognition of offspring
Brain Res. Bull.
(1997)

K. Kendrick et al.

Intracranial dialysis measurement of oxytocin, monoamine and uric acid release from the olfactory bulb and substantia nigra of sheep during parturition, suckling, separation from lambs and eating

Brain Res.

(1988)

K. Kendrick et al.

Microdialysis measurement of oxytocin, aspartate, gamma-aminobutyric acid and glutamate release from the olfactory bulb of the sheep during vaginocervical stimulation

Brain Res.

(1988)

F. Lévy et al.

Olfactory regulation of maternal behavior in mammals

Horm. Behav.

(2004)

Y. Osako et al.

Oxytocin enhances presynaptic and postsynaptic glutamatergic transmission between rat olfactory bulb neurones in culture

Neurosci. Lett.

(2001)

A. Rosser et al.

The importance of central noradrenergic neurones in the formation of an olfactory memory in the prevention of pregnancy block

Neuroscience

(1985)

T. Sugai et al.

Subdivisions of the guinea-pig accessory olfactory bulb revealed by the combined method with immunohistochemistry, electrophysiological, and optical recordings

Neuroscience

(1997)

M. Taniguchi et al.

Properties of reciprocal synapses in the mouse accessory olfactory bulb

Neuroscience

(2001)

G. Yu et al.

The olfactory bulb: a critical site of action for oxytocin in the induction of maternal behaviour in the rat

Neuroscience

(1996)

G. Yu et al.

The action of oxytocin originating in the hypothalamic paraventricular nucleus on mitral and granule cells in the rat main olfactory bulb

Neuroscience

(1996)

K. Binns et al.

Changes in electrophysiological activity in the accessory olfactory bulb and medial amygdala associated with mate recognition in mice

Eur. J. Neurosci.

(2005)

P. Brennan et al.

Olfactory recognition: a simple memory system

Science

(1990)

P. Brennan et al.

Mammalian social odours: attraction and individual recognition

Philos. Trans. R. Soc. Lond. B Biol. Sci.

(2006)

P. Brennan et al.

Pheromonal communication in vertebrates

Nature

(2006)

Cited by (42)

Vasopressin receptor 1a, oxytocin receptor, and oxytocin knockout male and female mice display normal perceptual abilities towards non-social odorants
2023, Hormones and Behavior
Genetic knockouts of the vasopressin receptor 1a (Avpr1a), oxytocin receptor (Oxtr), or oxytocin (Oxt) gene in mice have helped cement the causal relationship between these neuropeptide systems and various social behaviors (e.g., social investigation, recognition, and communication, as well as territoriality and aggression). In mice, these social behaviors depend upon the olfactory system. Thus, it is critical to assess the olfactory capabilities of these knockout models to accurately interpret the observed differences in social behavior. Prior studies utilizing these transgenic mice have sought to test for baseline deficits in olfactory processing; predominantly through use of odor habituation/dishabituation tasks, buried food tests, or investigation assays using non-social odorants. While informative, these assays rely on the animal's intrinsic motivation and locomotor behavior to measure olfactory capabilities and thus, often yield mixed results. Instead, psychophysical analyses using operant conditioning procedures and flow-dilution olfactometry are ideally suited to precisely quantify olfactory perception. In the present study, we used these methods to assess the main olfactory capabilities of adult male and female Avpr1a, Oxtr, and Oxt transgenic mice to volatile non-social odorants. Our results indicate that homozygous and heterozygous knockout mice of all three strains have the same sensitivity and discrimination ability as their wild-type littermates. These data strongly support the hypothesis that the observed social deficits of these global knockout mice are not due to baseline deficits of their main olfactory system.
Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles
2022, Current Biology
Social relationships are dynamic and evolve with shared and personal experiences. Whether the functional role of social neuromodulators also evolves with experience to shape the trajectory of relationships is unknown. We utilized pair bonding in the socially monogamous prairie vole as an example of socio-sexual experience that dramatically alters behaviors displayed toward other individuals. We investigated oxytocin-dependent modulation of excitatory synaptic transmission in the nucleus accumbens as a function of pair-bonding status. We found that an oxytocin receptor agonist decreases the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in sexually naive virgin, but not pair-bonded, female voles, while it increases the amplitude of electrically evoked EPSCs in paired voles, but not in virgins. This oxytocin-induced potentiation of synaptic transmission relies on the de novo coupling between oxytocin receptor signaling and endocannabinoid receptor type 1 (CB1) receptor signaling in pair-bonded voles. Blocking CB1 receptors after pair-bond formation increases the occurrence of a specific form of social rejection—defensive upright response—that is displayed toward the partner, but not toward a novel individual. Altogether, our results demonstrate that oxytocin’s action in the nucleus accumbens is changed through social experience in a way that regulates the trajectory of social interactions as the relationship with the partner unfolds, potentially promoting the maintenance of a pair bond by inhibiting aggressive responses. These results provide a mechanism by which social experience and context shift oxytocinergic signaling to impact neural and behavioral responses to social cues.
Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation
2021, Cell Reports
Oxytocin is a well-known neurohypophysial hormone that plays an important role in behavioral anxiety and nociception. Two major forms of long-term potentiation, presynaptic LTP (pre-LTP) and postsynaptic LTP (post-LTP), have been characterized in the anterior cingulate cortex (ACC). Both pre-LTP and post-LTP contribute to chronic-pain-related anxiety and behavioral sensitization. The roles of oxytocin in the ACC have not been studied. Here, we find that microinjections of oxytocin into the ACC attenuate nociceptive responses and anxiety-like behavioral responses in animals with neuropathic pain. Application of oxytocin selectively blocks the maintenance of pre-LTP but not post-LTP. In addition, oxytocin enhances inhibitory transmission and excites ACC interneurons. Similar results are obtained by using selective optical stimulation of oxytocin-containing projecting terminals in the ACC in animals with neuropathic pain. Our results demonstrate that oxytocin acts on central synapses and reduces chronic-pain-induced anxiety by reducing pre-LTP.
Receptor for advanced glycation end-products (RAGE) plays a critical role in retrieval behavior of mother mice at early postpartum
2021, Physiology and Behavior
Citation Excerpt :
For dams, one of the important cues are pups’ USVs, which can be both developmentally regulated and modulated by OT [67]. OT may be potentially involved in odor memory formation in parental behavior [71,74–76]. For instance, OT is associated with increased parent-child synchrony and sensitive touching.
Receptor for advanced glycation end-products (RAGE) is a pattern recognition molecule belonging to the immunoglobulin superfamily, and it plays a role in the remodeling of endothelial cells under pathological conditions. Recently, it was shown that RAGE is a binding protein for oxytocin (OT) and a transporter of OT to the brain on neurovascular endothelial cells via blood circulation. Deletion of the mouse RAGE gene, Ager (RAGE KO), induces hyperactivity in male mice. Impairment of pup care by mother RAGE KO mice after stress exposure results in the death of neonates 1–2 days after pup birth. Therefore, to understand the role of RAGE during the postpartum period, this study aims to examine parental behavior in female RAGE KO mice and ultrasonic vocalizations in pups. RAGE KO mothers without stress before delivery raised their pups and displayed hyperactivity at postpartum day (PPD) 3. KO dams showed impaired retrieval or interaction behavior after additional stress, such as body restraint stress or exposure to a novel environment, but such impaired behavior disappeared at PPD 7. Postnatal day 3 pups emitted ultrasonic vocalizations at >60 kHz as a part of the mother-pup relationship, but the number and category of calls by RAGE KO pups were significantly lower than wild-type pups. The results indicate that RAGE is important in the manifestation of normal parental behavior in dams and for receiving maternal care by mouse pups; moreover, brain OT recruited by RAGE plays a role in damping of signals of additional external stress and endogenous stress during the early postpartum period. Thus, RAGE-dependent OT may be critical for initiating and maintaining the normal mother-child relationship.
Dynamic regulation of oxytocin neuronal circuits in the sequential processes of prosocial behavior in rodent models
2021, Current Research in Neurobiology
The expression of positive social (i.e., prosocial) behavior is governed by a multitude of sensory and cognitive abilities to identify and recognize key features of potential social partners, elucidate social and individual status, and maintain appropriate behaviors. Oxytocin (OT) is a neuropeptide that has been implicated as a major player in regulating prosocial behavior, and much of its role in social situations has been uncovered. As social behavior inherently comprises sequential processes related to multimodal assessments of interactive features, a comprehensive approach to understanding the functions of OT in these prosocial behavior sequences is required. Here, the author discusses recent evidence illustrating the functioning of OT neural circuits in the processing of multimodal components of social behavior, including the detection/recognition of social cues via the olfactory bulb through olfactory cortices, evaluation of social features via the circuits of the paraventricular nucleus of the hypothalamus to the medial amygdala, and maintenance of prosocial behaviors via the circuits of the ventral tegmental area to the nucleus accumbens. A review of rodent studies with an emphasis on mice and rats is also provided to investigate the effects of OT in interaction with other neurotransmitters, such as serotonin and dopamine, to characterize the neuromodulatory mechanisms that mediate the sequences of prosocial engagements. The review further highlights OT function as a temporal dynamic of specific neural circuits.
A reproductive role for the nonapeptides vasotocin and isotocin in male zebrafish (Danio rerio)
2019, Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
Citation Excerpt :
This notion is supported by studies in mammals. In rats, for example, oxytocin enhances social recognition by modulating cortical control of early olfactory processing, at least in part by modulating long-term potentiation at the mitral to granule cell synapse (Dluzen et al., 1998; Fang et al., 2008; Oettl et al., 2016). The identification of isotocinergic signal in the peri-glomerular and glomerular layers of the adult male zebrafish OB in our study raises the possibility that a top-down regulation of isotocin may regulate sensitivity or habituation to olfactory (reproductive) cues.
Two distinct nonapeptide systems, vasotocin- and oxytocin-related peptides, evolved in vertebrates. Their role in male zebrafish reproduction has not been formally investigated. We hypothesized that the teleost nonapeptides vasotocin and isotocin stimulate male zebrafish reproductive physiology and success by affecting central neuronal and/or peripheral endocrine pathways. Pharmacological inhibition experiments revealed that both vasotocin and isotocin contribute significantly to male reproductive success, which in the case of vasotocin correlated significantly with indices of male courtship behavior. Interestingly, co-administration of vasotocin and isotocin antagonists completely abolished male reproductive success without affecting male courtship behavior and endocrine indices, possibly linked to a synergistic action of nonapeptides on male pheromone release. To further probe the nonapeptides' role in male zebrafish reproduction, we subsequently tested whether male zebrafish nonapeptide systems were acutely activated by the female releaser pheromone PGF_2α, a strong chemoattractant and important reproductive cue in males which stimulates courtship behavior. Male zebrafish attracted to PGF_2α in a choice assay exhibited acute increases in neuronal activation marker p-ERK immunoreactivity in the ventral glomerulus of the olfactory bulb and the preoptic area, however no co-localization with isotocin was observed. Conversely, PGF_2α time-dependently stimulated whole brain isotocin mRNA abundance, suggesting secondary longer-term effects of PGF_2α exposure on the central isotocinergic system. While the current lack of vasotocin-specific antibodies for zebrafish does not allow to probe acute activation of vasotocinergic neurons, whole brain vasotocin mRNA was not significantly affected by PGF_2α exposure. Together, our results identify a role for nonapeptides in male zebrafish reproductive physiology and success.

View all citing articles on Scopus

View full text

Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb

Abstract

Section snippets

Acknowledgements

Horm. Behav.

Neuroscience

Neuroscience

Prog. Neurobiol.

Front. Neuroendocrinol.

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Brain Res. Bull.

Brain Res.

Brain Res.

Horm. Behav.

Neurosci. Lett.

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Changes in electrophysiological activity in the accessory olfactory bulb and medial amygdala associated with mate recognition in mice

Eur. J. Neurosci.

Olfactory recognition: a simple memory system

Science

Mammalian social odours: attraction and individual recognition

Philos. Trans. R. Soc. Lond. B Biol. Sci.

Pheromonal communication in vertebrates

Nature