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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]

Snake vomeronasal receptor neurons in slice preparations were studied using the patch-clamp technique in the conventional and nystatin-perforated whole-cell configurations. The mean resting potential was approximately –70 mV; the average input resistance was 3 GΩ. Neurons required current injection of only 1–10 pA to display a variety of spiking patterns. Intracellular dialysis of 100 μM inositol 1,4,5-trisphosphate (IP[sub 3]) evoked an inward current in 38% of neurons, with an average peak amplitude of 16.4 ± 2.8 pA at a holding potential of –70mV. Application of 100 μM 3-deoxy-3-fluoro- d- myo-inositol 1,4,5-trisphosphate (F-IP[sub 3]), a derivative of IP[sub 3], also evoked an inward current in 4/8 (50%) neurons (32.6 ± 58 pA at –70 mV, n = 4). The reversal potentials of the induced components were estimated to be –14 ± 5 mV for IP[sub 3] and –17 ± 3 mV for F-IP[sub 3]. Bathing the neurons in 10 μM ruthenium red solution greatly reduced the IP[sub 3]-evoked inward current to 1.6 ± 1.1 pA at –70 mV ( n = 6). With Cs[sup +]-containing internal solution, neither the Ca[sup 2+]-ATPase inhibitor thapsigargin (1–50 μM) nor the Ca[sup 2+]-ionophore ionomycin (10 μM) evoked a significant current response, suggesting that IP[sub 3] can elicit current response in the neurons without mediation by intracellular Ca[sup 2+] stores. Intracellular application of 1 mM cAMP evoked no detectable current response. Extracellular application of chemoattractant for snakes evoked a very large inward current. The reversal potential of the chemoattractant-induced current was similar to that of the IP[sub 3]-induced current. The present results suggest that IP[sub 3] may act as a second messenger in the transduction of chemoattractants in the garter snake vomeronasal organ. [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.)