Neurosci Lett. 2016 Nov 10;634:107-113. doi: 10.1016/j.neulet.2016.09.056.

Activation of arginine vasopressin receptor 1a facilitates the induction of long-term potentiation in the accessory olfactory bulb of male mice.

Namba T1, Taniguchi M1, Murata Y1, Tong J2, Wang Y1, Okutani F2, Yamaguchi M1, Kaba H3.

1Department of Physiology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
2Department of Physiology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan; Department of Occupational Health, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
3Department of Physiology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. Electronic address: kabah@kochi-u.ac.jp.

 

Abstract

Olfaction plays an important role in social recognition in most mammals. Central arginine vasopressin (AVP) plays a role in this olfaction-based recognition. The high level of expression of AVP receptors in the accessory olfactory bulb (AOB) at the first relay of the vomeronasal system highlights the importance of AVP signaling at this stage. We therefore analyzed the effects of AVP on the synaptic plasticity of glutamatergic transmission from mitral cells to granule cells in AOB slices from male mice. To monitor the strength of the glutamatergic transmission, we measured the maximal initial slope of the lateral olfactory tract-evoked field potential, which represents the granule cell response to mitral cell activation. AVP paired with 100-Hz stimulation that only produced short-term potentiation enhanced the induction of long-term potentiation (LTP) in a dose-dependent manner. AVP-paired LTP was blocked by the selective AVP receptor 1a (AVPR1a) antagonist, d(CH2)5[Tyr(Me)2]AVP (Manning compound), but not by the AVPR1b antagonist SSR149415, and it was mimicked by the selective AVPR1a agonist [Phe2, Ile3, Orn8]-vasopressin. We further examined the effect of AVP on the reciprocal transmission between mitral and granule cells by stimulating a mitral cell and recording the evoked inhibitory postsynaptic currents (IPSCs) from the same cell using conventional whole-cell patch-clamp techniques. AVP reduced the reciprocal IPSCs triggered by endogenous glutamate release from the excited mitral cell. These results suggest that AVP promotes the induction of LTP at the mitral-to-granule cell synapse via the activation of AVPR1a through an as-yet-to-be-determined mechanism in the AOB of male mice.

KEYWORDS:

Accessory olfactory bulb; Dendrodendritic inhibition; Long-term potentiation; Reciprocal synapse; Vasopressin; Vasopressin receptor

PMID: 27697521

 

Supplement:

Central AVP and its receptors

In addition to its well established systemic physiological effects, the neuropeptide arginine vasopression (AVP) is a potent neuromodulator of social behavior in a variety of vertebrate taxa. Central AVP is expressed in parvocellular cells in the paraventricular nucleus, suprachiasmatic nucleus, bed nucleus of the stria terminalis, medial amygdala, medial septum, lateral septum, the vertical limb of the nucleus of the diagonal band of Broca and the locus coeruleus, and acts on two subtypes of AVP receptors (AVPRs): AVPR1a and AVPR1b. AVPR1a is found in a variety of brain nuclei, whereas AVPR1b appears to be discretely localized with a prominent expression in the CA2 pyramidal neurons of the hippocampus.

 

Behavioral relevance of olfactory AVP signaling

Central AVP facilitates social recognition and modulates a multitude of social behaviors in mammals, including parental behavior, aggression, affiliation and pair-bonding [1,2]. Social recognition involves the sensing, incorporation, integration, recognition and processing of information about conspecifics, and is mediated mainly by two anatomically distinct chemosensory systems in most mammals: the main olfactory system and the vomeronasal system [3]. The accessory olfactory bulb (AOB) at the first relay of the vomeronasal system has been demonstrated to be a critical site for mating-induced mate recognition in female mice [4]. However, the role of the AOB in male mice in social recognition is largely unknown. Microcircuits in the AOB include the prominent dendrodendritic reciprocal synapse between mitral cells, a single class of projection neurons, and granule cell interneurons. Glutamate released from mitral cell dendrites activates the dendrites of granule cells, which in turn mediate GABAergic dendrodendritic inhibition back onto mitral cell dendrites. This feedback inhibition at the reciprocal synapses regulates mitral cell activity.

 

AVP promotes synaptic plasticity in the AOB

The distribution of AVPR1a is different between vole species; monogamous prairie voles have a higher density of AVPR1a in the AOB compared to promiscuous montane voles [5]. Additionally, AVP plays a more prominent role in social recognition in males, whereas oxytocin is more important in females. These findings raise the possibility that AVP in the AOB is involved in synaptic plasticity that underlies social recognition in male mice. We tested this possibility by analyzing the effects of AVP on the synaptic plasticity of glutamatergic transmission from mitral cells to granule cells in AOB slices from male mice. The results show that AVP promotes the induction of long-term potentiation (LTP) of synaptic strength at the mitral-to-granule cell synapse via the activation of AVPR1a.

 

A hypothetical model for switching from infanticide to parental behavior

The vomeronasal system mediates instinctive sexual, nurturing, and fighting behaviors, hormonal responses, behavioral transition from infanticide to parenting, and individual recognition [6-13]. What aspects of these complex behaviors are associated with AVP-induced LTP in the AOB? Considering that monogamous prairie voles have a higher density of AVPR1a in the AOB compared to promiscuous montane voles and that synaptic plasticity within the AOB is necessary and sufficient to form the mate recognition memory in female mice, AVP signaling in the AOB is likely to be involved in social affiliation and learning. Of particular interest in this regard is the possibility that AVP release in the AOB acts to gate social chemosignal information to facilitate the radical behavior shift from infanticide to parental behavior in male mice.

 

It is envisaged that the tightly coupled feedback inhibition acting on mitral cells could act as a gate to control the transmission of the pups’ chemosignals leading to infanticide. During learning, the association of the chemosignals from a pregnant female with increased levels of AVP in the AOB after mating induces LTP at the mitral-to-granule cell side of the reciprocal synapses that are activated by the female’s chemosignals. The LTP would lead to a sequence of changes in the morphology of the reciprocal synapses and an increased release of the inhibitory neurotransmitter GABA in the AOB. After learning, the subpopulation of mitral cells that respond to the chemosignals from the female and her pups would be subject to enhanced feedback inhibition from granule cells via the potentiated synapses. The enhanced feedback inhibition onto the subpopulation of mitral cells would selectively inhibit the transmission of the pup chemosignals at the level of the AOB, preventing it from activating the neural pathway leading to infanticide.

 

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