Premium
Differential regulation of GABA release and neuronal excitability mediated by neuropeptide Y 1 and Y 2 receptors in rat thalamic neurons
Author(s) -
Sun QianQuan,
Akk Gustav,
Huguenard John R.,
Prince David A.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0081j.x
Subject(s) - inhibitory postsynaptic potential , neuroscience , chemistry , gabaa receptor , receptor , hyperpolarization (physics) , g protein coupled inwardly rectifying potassium channel , gabab receptor , gabaergic , postsynaptic potential , biology , g protein , biochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
1 Neuropeptide Y (NPY) produced inhibitory effects on neurons of the thalamic reticular nucleus (RT; n = 18 ) and adjacent ventral basal complex (VB; n = 22 ), which included hyperpolarization (∼4 mV), a reduction in rebound and regular spikes and an increased membrane conductance. These effects were mediated predominantly via NPY 1 receptor activation of G‐protein‐activated, inwardly rectifying K + (GIRK) channels. 2 NPY reduced the frequency of spontaneous GABA A receptor‐mediated inhibitory postsynaptic currents (sIPSCs) in RT (by 60 ± 7 %, n = 14 ) and VB neurons (by 25 ± 11 %, n = 16 ), but had no effect on the kinetic properties of sIPSCs. After removal of the RT nucleus, the inhibitory effects of NPY on sIPSCs in VB neurons remained (29 ± 7 %, n = 5 ). The synaptic effects were mediated via NPY 2 receptors. 3 NPY inhibited the frequency of miniature IPSCs (mIPSCs) in RT and VB neurons (by 63 ± 7 %, n = 5 , and 37 ± 8 %, n = 10 , respectively) in the presence of tetrodotoxin (TTX) (1 μM) but not TTX (1 μM) and Cd 2+ (200 μM). 4 NPY inhibited evoked IPSCs in both RT (by 18 ± 3 %, n = 6 ) and VB (by 5 ± 4 %, n = 6 ) neurons without change in short‐term synaptic plasticity. 5 We conclude that NPY 1 and NPY 2 receptors are functionally segregated in the thalamus: NPY 1 receptors are predominantly expressed at the somata and dendrites and directly reduce the excitability of neurons in both the RT and VB nuclei by activating GIRK channels. NPY 2 receptors are located at recurrent (RT) and feed‐forward GABAergic terminals (VB) and downregulate GABA release via inhibition of Ca 2+ influx from voltage‐gated Ca 2+ channels.