Dendritic colocalisation of serotonin1B receptors and the glutamate NMDA receptor subunit NR1 within the hippocampal dentate gyrus: An ultrastructural study

The serotonin1B receptor (5-HT1BR) plays a significant role in cognitive processing, which also involves glutamatergic transmission via N-methyl-d-aspartate (NMDA) receptors. It is implicated in a range of disorders, many of which also have a cognitive component, and therefore represents a valuable therapeutic target. 5-HT1BRs are described as predominantly pre-synaptic auto- and/or hetero-receptors, modulating the release of neurotransmitters including glutamate. However, a detailed assessment of localisation within the hippocampus, a pivotal structure in cognitive processing, has been absent. Here, we have conducted an electron microscopic examination of the subcellular distribution of the 5-HT1BR, NMDA receptor subunit NR1 and neurotransmitter γ-aminobutyric acid (GABA), within the hippocampal dentate gyrus. Ultrastructurally, 18% of 5-HT1BR immunoreactivity was pre-synaptic (within axons and axon terminals), and 65% post-synaptic (within dendrites and dendritic spines); no significant differences were found between molecular layer subdivisions. Post-synaptic labelling was cytoplasmic and membranous. Spinous labelling was more frequently bound to the plasma membrane, but not usually directly associated with the synaptic specialisation. Only 16% of 5-HT1BR positive profiles displayed NR1 labelling, of which most were dendrites, at a slightly higher level within the inner, compared to middle and outer molecular layer divisions. 5-HT1BR labelled profiles rarely showed labelling for GABA. These findings indicate that within the dentate gyrus, pre-synaptic 5-HT1BRs may modulate non-GABAergic neurotransmitter release whilst post-synaptic 5-HT1BRs are expressed on segments of mainly NR1 negative granule cell processes. However, a subpopulation of 5-HT1BRs is expressed on NR1 positive dendrites. Here, the 5-HT1BR may be an interesting target for modulation of NMDA receptor mediated currents.