期刊
NEUROPHARMACOLOGY
卷 148, 期 -, 页码 220-228出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.01.015
关键词
Nicotinic acetylcholine receptor; alpha 4 beta 2; alpha 7; Subthalamic nucleus; Dopamine receptors
资金
- Michael J. Fox Foundation [11345]
- National Institutes of Health [AG033954]
- California Tobacco Related Disease Research Program Grants
- National Natural Science Foundation of China [81701100, 81870891]
- Fund for Jiangsu Province Specially -Appointed Professor
- Natural Science Foundation of Jiangsu Province [BK20171160]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [17KJA320007, 18KJA320009]
- Jiangsu Province Fund for Dominant Discipline (Anesthesiology)
The subthalamic nucleus (STN) possesses microcircuits distinguished by subtypes of nicotinic acetylcholine receptors (nAChRs). Although dysfunction of the STN is well-known in Parkinson's disease, there is still little information about whether dopamine differentially modulates excitatory and inhibitory synaptic inputs to STN neurons expressing different nAChR subtypes. To address this issue, we performed brain slice patch-clamp recordings on STN neurons, while we pharmacologically manipulated dopaminergic inputs. In STN neuron subsets containing either alpha 4 beta 2 or alpha 7 nAChRs, D-1 and D-2 receptors respectively enhanced and inhibited spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs) and firing rates. The elevation of dopamine levels resulted in diverse regulations of synaptic transmission in these two neuron subsets, and interestingly, the dopamine regulation of sIPSCs significantly correlated with that of sEPSCs. Surprisingly, depletion of dopamine either by reserpine treatment or by unilateral 6-OHDA lesion of nigrostriatal dopaminergic neurons did not alter synaptic inputs to STN neurons, but STN neurons in the 6-OHDA-lesioned side exhibited hyperactivity. In summary, dopamine regulated both GABAergic and glutamatergic synaptic inputs to STN neuron subsets containing either alpha 4 beta 2 or alpha 7 nAChRs, forming a balancing machinery to control neuronal activity. In parkinsonian mice, postsynaptic mechanisms may exist and contribute to the hyperactivity of STN neurons.
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