Regulation of synaptic currents by m<scp>G</scp>lu<scp>R</scp>2 at reciprocal synapses in the mouse accessory olfactory bulb

<jats:title>Abstract</jats:title><jats:p>The throughput of information from the accessory olfactory bulb (<jats:styled-content style="fixed-case">AOB</jats:styled-content>) to downstream structures is controlled by reciprocal dendrodendritic inhibition of mitral cells by granule cells. Given the high expression levels of m<jats:styled-content style="fixed-case">G</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2, a metabotropic glutamate receptor, in the <jats:styled-content style="fixed-case">AOB</jats:styled-content> and the fact that the activation of m<jats:styled-content style="fixed-case">G</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2 permits the formation of a specific olfactory memory, we reasoned that m<jats:styled-content style="fixed-case">G</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2 might play an important role in regulating dendrodendritic inhibition. To test this hypothesis, we examined the effects of pharmacological and genetic manipulations of m<jats:styled-content style="fixed-case">G</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2 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<jats:styled-content style="fixed-case">V</jats:styled-content> 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 (<jats:styled-content style="fixed-case">mG</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2/<jats:styled-content style="fixed-case">mG</jats:styled-content>luR3), <jats:styled-content style="fixed-case">DCG</jats:styled-content>‐<jats:styled-content style="fixed-case">IV</jats:styled-content> [(2<jats:styled-content style="fixed-case">S</jats:styled-content>,1′<jats:styled-content style="fixed-case">R</jats:styled-content>,2′<jats:styled-content style="fixed-case">R</jats:styled-content>,3′<jats:styled-content style="fixed-case">R</jats:styled-content>)‐2‐(2,3‐dicarboxycyclopropyl)glycine], suppressed, whereas the m<jats:styled-content style="fixed-case">G</jats:styled-content>luR2/m<jats:styled-content style="fixed-case">G</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>3 antagonist LY341495 [(αS)‐α‐amino‐α‐[(1S,2S)‐2‐carboxycyclopropyl]‐9H‐xanthine‐9‐propanoic acid] enhanced dendrodendritic inhibition. Genetic ablation of <jats:styled-content style="fixed-case">mG</jats:styled-content>lu<jats:styled-content style="fixed-case">R</jats:styled-content>2 markedly impaired the effects of <jats:styled-content style="fixed-case">DCG</jats:styled-content>‐<jats:styled-content style="fixed-case">IV</jats:styled-content> and <jats:styled-content style="fixed-case">LY</jats:styled-content>341495 on dendrodendritic inhibition. <jats:styled-content style="fixed-case">DCG</jats:styled-content>‐<jats:styled-content style="fixed-case">IV</jats:styled-content> reduced both the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents recorded from granule cells. Additionally, <jats:styled-content style="fixed-case">DCG</jats:styled-content>‐<jats:styled-content style="fixed-case">IV</jats:styled-content> inhibited high‐voltage‐activated calcium currents in both mitral and granule cells. These results suggest that m<jats:styled-content style="fixed-case">G</jats:styled-content>luR2 reduces dendrodendritic inhibition by inhibiting synaptic transmission between mitral cells and granule cells in the <jats:styled-content style="fixed-case">AOB</jats:styled-content>.</jats:p>