Du Wenting, Stern Javier E, Filosa Jessica A
Department of Physiology, Georgia Regents University, Augusta, Georgia 30912.
Department of Physiology, Georgia Regents University, Augusta, Georgia 30912
J Neurosci. 2015 Apr 1;35(13):5330-41. doi: 10.1523/JNEUROSCI.3674-14.2015.
The classical model of neurovascular coupling (NVC) implies that activity-dependent axonal glutamate release at synapses evokes the production and release of vasoactive signals from both neurons and astrocytes, which dilate arterioles, increasing in turn cerebral blood flow (CBF) to areas with increased metabolic needs. However, whether this model is applicable to brain areas that also use less conventional neurotransmitters, such as neuropeptides, is currently unknown. To this end, we studied NVC in the rat hypothalamic magnocellular neurosecretory system (MNS) of the supraoptic nucleus (SON), in which dendritic release of neuropeptides, including vasopressin (VP), constitutes a key signaling modality influencing neuronal and network activity. Using a multidisciplinary approach, we investigated vasopressin-mediated vascular responses in SON arterioles of hypothalamic brain slices of Wistar or VP-eGFP Wistar rats. Bath-applied VP significantly constricted SON arterioles (Δ-41 ± 7%) via activation of the V1a receptor subtype. Vasoconstrictions were also observed in response to single VP neuronal stimulation (Δ-18 ± 2%), an effect prevented by V1a receptor blockade (V2255), supporting local dendritic VP release as the key signal mediating activity-dependent vasoconstrictions. Conversely, osmotically driven magnocellular neurosecretory neuronal population activity leads to a predominant nitric oxide-mediated vasodilation (Δ19 ± 2%). Activity-dependent vasodilations were followed by a VP-mediated vasoconstriction, which acted to limit the magnitude of the vasodilation and served to reset vascular tone following activity-dependent vasodilation. Together, our results unveiled a unique and complex form of NVC in the MNS, supporting a competitive balance between nitric oxide and activity-dependent dendritic released VP, in the generation of proper NVC responses.
经典的神经血管耦合(NVC)模型表明,突触处依赖活动的轴突谷氨酸释放会引发神经元和星形胶质细胞产生并释放血管活性信号,这些信号会使小动脉扩张,进而增加流向代谢需求增加区域的脑血流量(CBF)。然而,该模型是否适用于也使用不太常规神经递质(如神经肽)的脑区,目前尚不清楚。为此,我们研究了视上核(SON)的大鼠下丘脑大细胞神经分泌系统(MNS)中的NVC,其中包括血管加压素(VP)在内的神经肽的树突释放构成了影响神经元和网络活动的关键信号传导方式。我们采用多学科方法,研究了Wistar或VP-eGFP Wistar大鼠下丘脑脑片SON小动脉中血管加压素介导的血管反应。浴加VP通过激活V1a受体亚型显著收缩了SON小动脉(Δ-41±7%)。对单个VP神经元刺激也观察到血管收缩(Δ-18±2%),V1a受体阻断剂(V2255)可阻止这种效应,支持局部树突VP释放作为介导依赖活动的血管收缩的关键信号。相反,渗透压驱动的大细胞神经分泌神经元群体活动会导致主要由一氧化氮介导的血管舒张(Δ19±2%)。依赖活动的血管舒张之后是VP介导的血管收缩,其作用是限制血管舒张的幅度,并在依赖活动的血管舒张后重置血管张力。总之,我们的结果揭示了MNS中一种独特而复杂的NVC形式,支持在产生适当的NVC反应时,一氧化氮与依赖活动的树突释放VP之间的竞争平衡。