期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 123, 期 2, 页码 670-681出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00500.2019
关键词
5-HT1B receptor; GABA(A) receptor; GABA(B) receptor; lateral amygdala; serotonin
资金
- KAKENHI [18K07572, 18KK0468, 19K16192, 19K09918, 17H02223]
- Kanazawa Medical University [C2018-1]
- Nakatomi Foundation
- National Institute of Mental Health [MH-119854]
- Grants-in-Aid for Scientific Research [18K07572, 17H02223, 18KK0468, 19K16192, 19K09918] Funding Source: KAKEN
Much evidence implicates the serotonergic regulation of the amygdala in anxiety. Thus the present study was undertaken to characterize the influence of serotonin (5-HT) on principal neurons (PNs) of the rat lateral amygdala (LA). using whole cell recordings in vitro. Because inhibition is a major determinant of PN activity, we focused on the control of GABAergic transmission by 5-HT. IPSCs were elicited by local electrical stimulation of LA in the presence of glutamate receptor antagonists. We found that 5-HT reduces GABA(A) inhibitory postsynaptic currents (IPSCs) via presynaptic 5-HT1B, receptors. While the presynaptic inhibition of GABA release also attenuated GABA(B) currents, this effect was less pronounced than for GABA(A) currents because 5-HT also induced a competing postsynaptic enhancement of GABA(B) currents. That is, GABA(B) currents elicited by pressure application of GABA or baclofen were enhanced by 5-HT. In addition, we obtained evidence suggesting that 5-HT differentially regulates distinct subsets of GABAergic synapses. Indeed, GABA(A) IPSCs were comprised of two components: a relatively 5-HT-insensitive IPSC that had a fast time course and a 5-HT-insensitive component that had a slower time course. Because the relative contribution of these two components varied depending on whether neurons were recorded at proximity versus at a distance from the stimulating electrodes, we speculate that distinct subtypes of local-circuit cells contribute the two contingents of GABAergic synapses. Overall, our results indicate that 5-HT is a potent regulator of synaptic inhibition in LA. NEW & NOTEWORTHY We report that 5-HT. acting via presynaptic 5-HT IB receptors. attenuates GABA A IPSCs by reducing GABA release in the lateral amygdala (LA). In parallel, 5-HT enhances GABA B currents postsynaptically, such that GABA B inhibitory postsynaptic currents (IPSCs) are relatively preserved from the presynaptic inhibition of GABA release. We also found that the time course of 5-HT-sensitive and -insensitive GABA A IPSCs differ. Together, these results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.
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