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M1/M3 Muscarinic Acetylcholine Receptors Control Long-Term, but Not Short-Term Plasticity at the Mossy Fiber – CA3 Pyramidal Cell Synapse in Mouse Hippocampus
Version 1
: Received: 14 June 2023 / Approved: 15 June 2023 / Online: 15 June 2023 (12:39:05 CEST)
Version 2
: Received: 13 July 2023 / Approved: 13 July 2023 / Online: 14 July 2023 (09:24:01 CEST)
Zheng, F.; Wess, J.; Alzheimer, C. Long-Term—But Not Short-Term—Plasticity at the Mossy Fiber–CA3 Pyramidal Cell Synapse in Hippocampus Is Altered in M1/M3 Muscarinic Acetylcholine Receptor Double Knockout Mice. Cells2023, 12, 1890.
Zheng, F.; Wess, J.; Alzheimer, C. Long-Term—But Not Short-Term—Plasticity at the Mossy Fiber–CA3 Pyramidal Cell Synapse in Hippocampus Is Altered in M1/M3 Muscarinic Acetylcholine Receptor Double Knockout Mice. Cells 2023, 12, 1890.
Zheng, F.; Wess, J.; Alzheimer, C. Long-Term—But Not Short-Term—Plasticity at the Mossy Fiber–CA3 Pyramidal Cell Synapse in Hippocampus Is Altered in M1/M3 Muscarinic Acetylcholine Receptor Double Knockout Mice. Cells2023, 12, 1890.
Zheng, F.; Wess, J.; Alzheimer, C. Long-Term—But Not Short-Term—Plasticity at the Mossy Fiber–CA3 Pyramidal Cell Synapse in Hippocampus Is Altered in M1/M3 Muscarinic Acetylcholine Receptor Double Knockout Mice. Cells 2023, 12, 1890.
Abstract
Muscarinic acetylcholine receptors are well-known for their crucial involvement in hippocampus-dependent learning and memory, but the exact roles of the various receptor subtypes (M1-M5) are still not fully understood. Here, we studied how M1 and M3 receptors affect plasticity at the mossy fiber (MF)-CA3 pyramidal cell syn-apse. In hippocampal slices from M1/M3 receptor double knockout (M1/M3-dKO) mice, the signature short-term plasticity of the MF-CA3 synapse was not significantly affected. However, the rather unique, NMDA receptor-independent and presynaptic form of long-term potentiation (LTP) of this synapse was much larger in M1/M3-deficient slices compared to wild type slices, in both field potential and whole-cell recordings. Consistent with its presynaptic origin, induction of MF-LTP strongly en-hanced the excitatory drive onto single CA3 pyramidal cells, with the effect being more pronounced in M1/M3-dKO cells. In an earlier study (Zheng et al., 2012), we found that deletion of M2 receptors in mice disinhibits MF-LTP in a similar fashion, suggesting that endogenous acetylcholine employs both M1/M3 and M2 receptors to constrain MF-LTP. Importantly, such synergism was not observed for MF long-term depression (LTD). Low-frequency stimulation, which reliably induced LTD of MF synapses in control slices, failed to do so in M1/M3-dKO slices and gave rise to LTP instead. In striking contrast, loss of M2 augmented LTD when compared to control slices. Taken together, our data demonstrate convergence of M1/M3 and M2 recep-tors on MF-LTP, but functional divergence on MF-LTD, the net effect being well-balanced bidirectional plasticity of the MF-CA3 pyramidal cell synapse.
Biology and Life Sciences, Neuroscience and Neurology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
