1. Opposing effects of an atypical glycinergic and substance P transmission on interpeduncular nucleus plasticity.
- Author
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Melani R, Von Itter R, Jing D, Koppensteiner P, and Ninan I
- Subjects
- Animals, Electrophysiological Phenomena, Glutamic Acid metabolism, Inhibitory Postsynaptic Potentials physiology, Long-Term Potentiation physiology, Mice, Receptor, Cannabinoid, CB1 metabolism, Receptors, GABA-B metabolism, Receptors, Neurokinin-1 metabolism, Synaptic Transmission, Glycine metabolism, Habenula metabolism, Interpeduncular Nucleus metabolism, Neuronal Plasticity physiology, Neurons metabolism, Substance P metabolism
- Abstract
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway has recently been implicated in the suppression of fear memory. A notable feature of this pathway is the corelease of neurotransmitters and neuropeptides from MHb neurons. Our studies in mice reveal that an activation of substance P-positive dorsomedial habenula (dMHb) neurons results in simultaneous release of glutamate and glycine in the lateral interpeduncular nucleus (LIPN). This glycine receptor activity inhibits an activity-dependent long-lasting potentiation of glutamatergic synapses in LIPN neurons, while substance P enhances this plasticity. An endocannabinoid CB1 receptor-mediated suppression of GABA
B receptor activity allows substance P to induce a long-lasting increase in glutamate release in LIPN neurons. Consistent with the substance P-dependent synaptic potentiation in the LIPN, the NK1R in the IPN is involved in fear extinction but not fear conditioning. Thus, our study describes a novel plasticity mechanism in the LIPN and a region-specific role of substance P in fear extinction.- Published
- 2019
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