Metabotropic glutamate receptor 3 is downregulated and its expression is shifted from neurons to astrocytes in the mouse lateral septum during the postpartum period.

The inhibitory metabotropic glutamate receptor 3 (mGluR3) plays diverse and complex roles in brain function, including synaptic plasticity and neurotransmission. We recently found that mGluR3 is downregulated in the lateral septum (LS) of postpartum females using microarray and qPCR analysis. In this study, we used double fluorescence immunohistochemical approaches to characterize mGluR3 changes in LS of the postpartum brain. The number of mGluR3-immunoractive cells was significantly reduced in the dorsal (LSD) and intermediate (LSI) but not ventral (LSV) parts of the LS in postpartum versus virgin females. mGluR3 immunoreactivity in the LS was found predominantly in neurons (~70%), with a smaller portion (~20%-30%) in astrocytes. Colocalization analysis revealed a reduced mGluR3 expression in neurons but an increased astrocytic localization in postpartum LSI. This change in the pattern of expression suggests that mGluR3 expression is shifted from neurons to astrocytes in postpartum LS, and the decrease in mGluR3 is neuron-specific. Because mGluR3 is inhibitory and negatively regulates glutamate and GABA release, decreases in neuronal expression would increase glutamate and GABA signaling. Given our recent finding that ~90% of LS neurons are GABAergic, the present data suggest that decreases in mGluR3 are a mechanism for elevated GABA in LS in the postpartum state.