Cortically driven Fos induction in the striatum is amplified by local dopamine D2-class receptor blockade

Cortically driven Fos induction in the striatum is amplified by local dopamine D2-class receptor blockade
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DOI:
10.1046/j.1460-9568.1999.00866.x
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发表时间:
1999-12-01
影响因子:
3.4
通讯作者:
Graybiel, AM
Graybiel, AM
中科院分区:
医学3区
文献类型:
--
作者:
Berretta, S;Sachs, Z;Graybiel, AM

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多巴胺D2类受体已被证明可以控制纹状体神经元对皮质激活的兴奋性。然而,目前还不清楚这些受体是否可以调节皮层刺激激活的纹状体神经元的数量,从而影响纹状体对其皮层输入的群体反应。我们使用Fos诱导作为读数来测量纹状体神经元对额叶皮层局部刺激的整体反应,并测试D2类多巴胺受体阻断剂对这种反应的影响。在自由活动的大鼠中,我们通过局部硬膜外应用一定剂量的GABA(A)受体拮抗剂(印防己毒素)刺激额叶皮质,以诱导纹状体中的Fos。我们将这种治疗与D2类多巴胺受体拮抗剂治疗相结合,剂量水平也刚好是诱导Fos的阈值,使用(i)全身氟哌啶醇或(ii)纹状体内(-)舒必利。无论是系统和纹状体内阻断D2类受体急剧增加纹状体神经元表现出皮质诱发Fos诱导的数量。这些发现表明,纹状体内D2类多巴胺受体的局部激活可以调节纹状体神经元对皮质输入的反应数量,从而动态地塑造通过纹状体的信息流。
Dopamine D2-class receptors have been shown to control the excitability of striatal neurons in response to cortical activation. It has been unclear, however, whether such receptors could regulate the number of striatal neurons activated by cortical stimulation, and thus affect the population response of the striatum to its cortical inputs. We used Fos induction as a readout to measure the ensemble response of striatal neurons to localized stimulation of the frontal cortex and tested for the effects of D2-class dopamine receptor blockade on this response. In freely moving rats, we stimulated the frontal cortex by local epidural application of a dose of a GABA(A) receptor antagonist (picrotoxin) just threshold for inducing Fos in the striatum. We combined this treatment with D2-class dopamine receptor antagonist treatments at dose levels also just threshold for inducing Fos, using either (i) systemic haloperidol or (ii) intrastriatal (-)sulpiride. Both systemic and intrastriatal blockade of D2-class receptors sharply increased the numbers of striatal neurons exhibiting cortically evoked Fos induction. These findings suggest that local activation of intrastriatal D2-class dopamine receptors can regulate the number of striatal neurons responsive to cortical inputs, thus dynamically shaping the flow of information through the striatum.