Differential signalling induced by α7 nicotinic acetylcholine receptors in hippocampal dentate gyrus in vitro and in vivo

The activation of alpha 7 nicotinic acetylcholine receptors (nAChRs) has been shown to improve hippocampus-dependent learning and memory. alpha 7 nAChRs are densely expressed among several different cell types in the hippocampus, with high Ca2+ permeability, although it is unclear if alpha 7 nAChRs mobilize differential signalling mechanisms among distinct neuronal populations. To address this question, we compared alpha 7 nAChR agonist-induced responses (i.e. calcium and cAMP changes) between granule cells and GABAergic neurons in the hippocampal dentate gyrus both in vitro and in vivo. In cultured organotypic hippocampal slices, we observed robust intracellular calcium and cAMP increases in dentate granule cells upon activation of alpha 7 nAChRs. In contrast, GABAergic interneurons displayed little change in either calcium or cAMP concentration after alpha 7 nAChR activation, even though they displayed much larger alpha 7 nAChR current responses than those of dentate granule cells. We found that this was due to smaller alpha 7 nAChR-induced Ca2+ rises in GABAergic interneurons. Thus, the regulation of the Ca2+ transients in different cell types resulted in differential subsequent intracellular signalling cascades and likely the ultimate outcome of alpha 7 nAChR activation. Furthermore, wemonitored neuronal activities of dentate granule cells and GABAergic interneurons in vivo via optic fibre photometry. We observed enhancement of neuronal activities after nicotine administration in dentate granule cells, but not in GABAergic neurons, whichwas absent in alpha 7 nAChR-deficient granule cells. In summary, we reveal amechanism for alpha 7 nAChR-mediated increase of neuronal activity via cell type-specific intracellular signalling pathways.

Automated summary

The study compared the responses of dentate granule cells and GABAergic interneurons to α7 nAChR agonists, revealing differential effects on intracellular signaling pathways possibly due to variations in Ca2+ regulation in different cell types. Additionally, in vivo observations showed enhanced neuronal activity in dentate granule cells but not in GABAergic neurons after nicotine administration, indicating a cell type-specific mechanism for α7 nAChR-mediated increase of neuronal activity.