Cox C L, Huguenard J R, Prince D A
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305, USA.
J Neurosci. 1997 Jan 1;17(1):70-82. doi: 10.1523/JNEUROSCI.17-01-00070.1997.
Cholecystokinin (CCK)-mediated actions on intrathalamic rhythmic activities were examined in an in vitro rat thalamic slice preparation. Single electrical stimuli in the thalamic reticular nucleus (nRt) evoked rhythmic activity (1-15 sec duration) in nRt and the adjacent ventrobasal nucleus (VB). Low CCK concentrations (20-50 nM) suppressed rhythmic oscillations in 43% of experiments but prolonged such activities in the remaining slices. Higher CCK concentrations (100-400 nM) had a predominantly antioscillatory effect. Suppression of oscillations was associated with a relatively large membrane depolarization of nRt neurons that changed their firing mode from phasic (burst) to tonic (single-spike) output. This decreased burst discharge of nRt neurons during CCK application reduced inhibitory drive onto VB neurons from multiple peaked inhibitory postsynaptic currents (IPSCs) to single peaked inhibitory events. We hypothesize that suppression of inhibitory drive onto VB neurons decreases their probability of burst output, which, together with a reduction of nRt burst output, dampens the oscillatory activity. Low CCK concentrations, which produced little or no depolarization of nRt neurons, did not alter the firing mode of the nRt neurons. However, the probability of burst output from nRt neurons in response to subthreshold stimuli was increased in low CCK concentrations, presumably leading to an increase in the number of nRt neurons participating in the rhythmic activity. Our findings suggest that the neuropeptide CCK, by altering the firing characteristics of nRt neurons, has powerful modulatory effects on intrathalamic rhythms; the ultimate action was dependent on CCK concentration and resting state of these cells.
在体外大鼠丘脑切片标本中研究了胆囊收缩素（CCK）对丘脑内节律性活动的作用。在丘脑网状核（nRt）施加单个电刺激可诱发nRt及其相邻腹侧基底核（VB）的节律性活动（持续时间1 - 15秒）。低浓度CCK（20 - 50 nM）在43%的实验中抑制了节律性振荡，但在其余切片中延长了此类活动。较高浓度CCK（100 - 400 nM）主要具有抗振荡作用。振荡的抑制与nRt神经元相对较大的膜去极化有关，这改变了它们的放电模式，从相位性（爆发式）输出转变为紧张性（单峰式）输出。在应用CCK期间，nRt神经元爆发性放电的减少降低了从多个峰状抑制性突触后电流（IPSCs）到单个峰状抑制性事件对VB神经元的抑制驱动。我们推测，对VB神经元抑制驱动的抑制降低了它们爆发式输出的概率，这与nRt爆发式输出的减少一起，减弱了振荡活动。低浓度CCK对nRt神经元几乎没有或没有产生去极化，没有改变nRt神经元的放电模式。然而，在低浓度CCK下，nRt神经元对阈下刺激产生爆发式输出的概率增加，推测这导致参与节律性活动的nRt神经元数量增加。我们的研究结果表明，神经肽CCK通过改变nRt神经元的放电特性，对丘脑内节律具有强大的调节作用；最终作用取决于CCK浓度和这些细胞的静息状态。
