α₂-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

Abstract

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 patchclamp 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.

RNAseq Analysis of FABP4 Knockout Mouse Hippocampal Transcriptome Suggests a Role for WNT/β-Catenin in Preventing Obesity-Induced Cognitive Impairment

“…There were 19 transcripts in total ( Table 2 ). AKO mice fed HFD have upregulated transcripts associated with negative regulation of apoptosis [ 42 , 43 , 44 ], neuroinflammation [ 45 ], and ER stress [ 42 , 43 ] along with positive regulation of long-term potentiation [ 46 , 47 , 48 ], spatial working memory [ 49 ], synaptic plasticity [ 50 , 51 ], neurogenesis [ 52 , 53 ], and Wnt/β-Catenin signaling [ 54 ].…”

“…The BRD1 protein is needed for H3K14 acetylation [ 63 ], which is associated with synaptic plasticity [ 50 ]. The activation of α2-adrenergic receptors has been shown to promote long-term potentiation in the mouse brain [ 46 ]. Mice lacking MDGA1 and GRIK2 have exhibited compromised hippocampal long-term potentiation [ 47 , 48 ].…”

Noradrenaline depresses facial stimulation-evoked cerebellar MLI-PC synaptic transmission via α2-AR/PKA signaling cascade in vivo in mice

“…Activation of presynaptic α2-ARs inhibits N-type calcium channels, neurotransmitter release, and PKA activity, which in turn decreases phosphorylation of receptors 61 . Activation of α2-ARs suppresses the production of cAMP-dependent PKA; in turn, this activates protein phosphatase 1, which inhibits synaptic transmission 62 , 63 and reduces presynaptic glutamate release from mitral cells through Gi/o-protein-mediated inhibition of Ca 2+ channels in the mouse olfactory bulb 64 . In the cerebellar cortex, NA reduces glutamate release at CF-PC synapses via a presynaptic α2-AR-PKA signaling pathway in vitro in mouse 27 .…”

Effect of Noradrenaline on the Facial Stimulation-Evoked Mossy Fiber-Granule Cell Synaptic Transmission in Mouse Cerebellar Cortex

“…In the cerebellar cortex, α2-ARs play critical roles in information processing and motor coordination skills ( Lähdesmäki et al, 2002 ). A previous study demonstrated that activation of α2-ARs suppresses presynaptic glutamate release from mitral cells by a G i/o -protein-mediated inhibition of Ca 2+ channels in the mouse olfactory bulb ( Huang et al, 2018 ). We previously found that NA inhibits complex spike activity via a presynaptic PKA signaling pathway in vitro ( Cui et al, 2020 ).…”