A subpopulation of serotonin1B receptors colocalize with the AMPA receptor subunit GluR2 in the hippocampal dentate gyrus

The serotonin_1B receptor (5-HT_1BR) plays a role in cognitive processes that also involve glutamatergic neurotransmission via amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors. Accumulating experimental evidence also highlights the involvement of 5-HT_1BRs in several neurological disorders. Consequently, the 5-HT_1BR is increasingly implicated as a potential therapeutic target for intervention in cognitive dysfunction. Within the hippocampus, a brain region critical to cognitive processing, populations of pre- and post-synaptic 5-HT_1BRs have been identified. Thus, 5-HT_1BRs could have a role in the modulation of hippocampal pre- and post-synaptic conductance. Previously, we demonstrated colocalization of 5-HT_1BRs with the N-methyl-d-aspartate (NMDA) receptor subunit NR1 in a subpopulation of granule cell dendrites (Peddie et al. [53]). In this study, we have examined the cellular and subcellular distribution of 5-HT_1BRs with the AMPA receptor subunit GluR2. Of 5-HT_1BR positive profiles, 28% displayed colocalization with GluR2. Of these, 87% were dendrites, corresponding to 41% and 10% of all 5-HT_1BR labeled or GluR2 labeled dendrites, respectively. Dendritic labeling was both cytoplasmic and membranous but was not usually associated with synaptic sites. Colocalization within dendritic spines and axons was comparatively rare. These findings indicate that within the dentate gyrus molecular layer, dendritic 5-HT_1BRs are expressed predominantly on GluR2 negative granule cell processes. However, a subpopulation of 5-HT_1BRs is expressed on GluR2 positive dendrites. Here, it is suggested that activation of the 5-HT_1BR may play a role in the modulation of AMPA receptor mediated conductance, further supporting the notion that the 5-HT_1BR represents an interesting therapeutic target for modulation of cognitive function.