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The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB. Stimulation (400 stimuli) of MC axons at 10 Hz but not at 100 Hz effectively induced N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP), which exhibited reversibility. NA paired with subthreshold 10-Hz stimulation (200 stimuli) facilitated the induction of NMDA receptor-dependent LTP via the activation of a[subscript 2]-adrenergic receptors (ARs). We next examined how NA, acting at a[subscript 2]-ARs, facilitates LTP induction. In terms of acute actions, NA suppressed GC excitatory postsynaptic current (EPSC) responses to single pulse stimulation of MC axons by reducing glutamate release from MCs via G-protein coupled inhibition of calcium channels. Consequently, NA reduced recurrent inhibition of MCs, resulting in the enhancement of evoked EPSCs and spike fidelity in GCs during the 10-Hz stimulation used to induce LTP. These results suggest that NA, acting at a[subscript 2]-ARs, facilitates the induction of NMDA receptor-dependent LTP at the MC-to-GC synapse by shifting its threshold through disinhibition of MCs.

The throughput of information from the accessory olfactory bulb ( AOB) to downstream structures is controlled by reciprocal dendrodendritic inhibition of mitral cells by granule cells. Given the high expression levels of m Glu R2, a metabotropic glutamate receptor, in the AOB and the fact that the activation of m Glu R2 permits the formation of a specific olfactory memory, we reasoned that m Glu R2 might play an important role in regulating dendrodendritic inhibition. To test this hypothesis, we examined the effects of pharmacological and genetic manipulations of m Glu R2 on synaptic responses measured from mitral or granule cells in slice preparations from 23- to 36-day-old Balb/c mice. To evoke dendrodendritic inhibition, a depolarizing voltage step from -70 to 0 m V or a threshold current stimulus adjusted to elicit action potential(s) was applied to a mitral cell using either a nystatin-perforated or conventional whole-cell configuration. We found that an agonist for group II metabotropic glutamate receptors ( mGlu R2/ mGluR3), DCG- IV [(2 S,1′ R,2′ R,3′ R)-2-(2,3-dicarboxycyclopropyl)glycine], suppressed, whereas the m GluR2/m Glu R3 antagonist LY341495 [(αS)-α-amino-α-[(1S,2S)-2-carboxycyclopropyl]-9H-xanthine-9-propanoic acid] enhanced dendrodendritic inhibition. Genetic ablation of mGlu R2 markedly impaired the effects of DCG- IV and LY341495 on dendrodendritic inhibition. DCG- IV reduced both the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents recorded from granule cells. Additionally, DCG- IV inhibited high-voltage-activated calcium currents in both mitral and granule cells. These results suggest that m GluR2 reduces dendrodendritic inhibition by inhibiting synaptic transmission between mitral cells and granule cells in the AOB. [ABSTRACT FROM AUTHOR]

After training with an odour paired with foot shock on postnatal day 11, rat pups show an aversion to the odour in testing on postnatal day 12. The mechanisms underlying this aversive olfactory learning involve disinhibition of mitral/tufted cells in the olfactory bulb by the somatosensory stimulation-induced activation of centrifugal noradrenergic fibres originating in the locus coeruleus. The activity of mitral/tufted cells is regulated through γ-aminobutyric acidA (GABAA) receptors in the external plexiform layer and GABAB receptors in the glomerular layer. We have previously presented that aversive olfactory learning in young rats is modulated through GABAA receptors in the olfactory bulb. In the present study we examined the consequence of manipulating GABAB receptors in the olfactory bulb during training. Baclofen, a GABAB receptor agonist when infused into the olfactory bulb during the pairing of an odour with foot shock, prevented aversive olfactory learning in a dose-dependent manner. Infusion of saclofen, a GABAB receptor antagonist, during training with a citral odour in the absence of foot shock produced aversive responses not only to the odour, but also to strange odours (benzaldehyde and vanillin) not previously presented. Such olfactory aversions were observed even if saclofen was infused without odour exposure. These results suggest that olfactory learning in young rats is modulated through GABAB receptors in the olfactory bulb. [ABSTRACT FROM AUTHOR]

The olfactory bulb is critically involved in early olfactory learning. In this study, we examined the effect of intrabulbar infusion of ritanserin, a 5-hydroxytryptamine[sub 2] (5-HT[sub 2] ) receptor antagonist on a one-trial aversive olfactory learning in young rats. Ritanserin, a 5-HT[sub 2] receptor antagonist, was continuously infused into the olfactory bulb of postnatal day-11 (PND 11) rat pups during a 30-min training session of pairing citral odor and foot shock. On the following day, the time spent in the part of the apparatus where the odor was present was measured as an index of odor aversion. Consistent with a previous study on olfactory preference learning, 1 nM ritanserin, but not 10 nM, blocked the olfactory aversive learning. We further examined the ability of 10 nM ritanserin to induce olfactory learning in the absence of the unconditioned stimulus foot shock. Pups that received intrabulbar infusion of 10 nM ritanserin in the presence of citral odor developed an aversion to the odor without foot shock. Since ritanserin has been shown to have an affinity for dopamine receptors, we examined the effect of dopamine antagonists on the ritanserin-induced aversive olfactory learning. Co-infusion of the dopamine D[sub 1] receptor antagonist (±)-SKF-83566 with ritanserin dose-dependently prevented induced learning. In contrast, the D[sub 2] receptor antagonist spiperone was without effect. These results extend the previous finding on the role of bulbar 5-HT[sub 2] receptors in early olfactory learning and suggest that high concentration of ritanserin facilitates aversive olfactory learning through D[sub 1] receptors in the olfactory bulb. © 2000 John Wiley & Sons, Inc. Dev Psychobiol 37: 246–252, 2000 [ABSTRACT FROM AUTHOR]

The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB. Stimulation (400 stimuli) of MC axons at 10 Hz but not at 100 Hz effectively induced N -methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation (LTP), which exhibited reversibility. NA paired with subthreshold 10-Hz stimulation (200 stimuli) facilitated the induction of NMDA receptor-dependent LTP via the activation of α 2 -adrenergic receptors (ARs). We next examined how NA, acting at α 2 -ARs, facilitates LTP induction. In terms of acute actions, NA suppressed GC excitatory postsynaptic current (EPSC) responses to single pulse stimulation of MC axons by reducing glutamate release from MCs via G-protein coupled inhibition of calcium channels. Consequently, NA reduced recurrent inhibition of MCs, resulting in the enhancement of evoked EPSCs and spike fidelity in GCs during the 10-Hz stimulation used to induce LTP. These results suggest that NA, acting at α 2 -ARs, facilitates the induction of NMDA receptor-dependent LTP at the MC-to-GC synapse by shifting its threshold through disinhibition of MCs., (© 2018 Huang et al.; Published by Cold Spring Harbor Laboratory Press.)