Dopamine neurons make glutamatergic synapses in vitro
Dopamine neurons make glutamatergic synapses in vitro
复制标题
DOI：
10.1523/jneurosci.18-12-04588.1998
复制
发表时间：
1998-06-15
影响因子：
5.3
通讯作者：
Rayport, S
中科院分区：
文献类型：
--
作者：
Sulzer, D;Joyce, MP;Rayport, S
多巴胺和谷氨酸之间的相互作用在记忆、成瘾和精神分裂症中起着重要作用。一些证据表明，腹侧中脑多巴胺神经元，引起主要的中枢神经系统多巴胺能投射也可能是多巴胺能的。为了研究这种可能性，我们双重免疫染色的多巴胺合成酶酪氨酸羟化酶和谷氨酸从大鼠和猴子的中脑腹侧部分，我们发现，大多数多巴胺神经元免疫染色谷氨酸，无论是在大鼠和猴子。然后，我们使用出生后的细胞培养来检查单个多巴胺神经元。同样，大多数多巴胺神经元对谷氨酸免疫染色;它们对磷酸活化的谷氨酸脱氢酶也有免疫反应，磷酸活化的谷氨酸脱氢酶是神经递质谷氨酸的主要来源。抑制谷氨酰胺酶可减少谷氨酸染色。在单细胞微培养中，多巴胺神经元引起了静脉曲张免疫反应的酪氨酸羟化酶和谷氨酸和其他免疫反应主要是谷氨酸，这是发现附近的细胞体。在超微结构水平上，多巴胺神经元偶尔形成对称的突触特化的多巴胺能静脉曲张，但他们更常见的形成非多巴胺能静脉曲张与不对称的突触特化。单个多巴胺神经元的刺激诱发了一个快速的多巴胺能autaptic EPSC，表现出突触前抑制所造成的伴随多巴胺释放。因此，多巴胺神经元可以通过它们的多巴胺能突触发挥快速的突触作用，并通过它们的多巴胺能突触发挥较慢的调节作用。结合中缝核能神经元和去甲肾上腺素能蓝斑神经元谷氨酸共传递的证据，本研究结果表明，谷氨酸能共传递可能是中枢单胺能神经元的规则。
Interactions between dopamine and glutamate play prominent roles in memory, addiction, and schizophrenia. Several lines of evidence have suggested that the ventral midbrain dopamine neurons that give rise to the major CNS dopaminergic projections may also be glutamatergic. To examine this possibility, we double immunostained ventral midbrain sections from rat and monkey for the dopamine-synthetic enzyme tyrosine hydroxylase and for glutamate; we found that most dopamine neurons immunostained for glutamate, both in rat and monkey. We then used postnatal cell culture to examine individual dopamine neurons. Again, most dopamine neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmitter glutamate. Inhibition of glutaminase reduced glutamate staining. In single-cell microculture, dopamine neurons gave rise to varicosities immunoreactive for both tyrosine hydroxylase and glutamate and others immunoreactive mainly for glutamate, which were found near the cell body. At the ultrastructural level, dopamine neurons formed occasional dopaminergic varicosities with symmetric synaptic specializations, but they more commonly formed nondopaminergic varicosities with asymmetric synaptic specializations. Stimulation of individual dopamine neurons evoked a fast glutamatergic autaptic EPSC that showed presynaptic inhibition caused by concomitant dopamine release. Thus, dopamine neurons may exert rapid synaptic actions via their glutamatergic synapses and slower modulatory actions via their dopaminergic synapses. Together with evidence for glutamate cotransmission in serotonergic raphe neurons and noradrenergic locus coeruleus neurons, the present results suggest that glutamatergic cotransmission may be the rule for central monoaminergic neurons.