Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2.
Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2.
复制标题
DOI：
10.1038/mp.2014.47
复制
发表时间：
2015-04
影响因子：
11
通讯作者：
Young WS
中科院分区：
文献类型：
--
作者：
Pagani JH;Zhao M;Cui Z;Avram SK;Caruana DA;Dudek SM;Young WS
血管加压素1b受体（Avpr 1b）是啮齿类动物的社会记忆和社会攻击的关键，但很少有人知道它在这些行为中的具体作用。Avpr 1b功能的一些线索可以从其在大脑中的表达谱中获得，这在很大程度上限于海马CA 2区的锥体神经元，并从实验中显示基因的失活或受体的拮抗作用导致社会攻击性的减少。在这里，我们表明，通过慢病毒递送到背侧CA 2区域的Avpr 1b的部分替换恢复了Avpr 1b基因敲除小鼠的社会动机攻击行为的概率，而不改变焦虑样行为。为了进一步探索Avpr 1b在海马区的作用，我们研究了Avpr 1b激动剂对小鼠和大鼠海马切片中锥体神经元的影响。我们发现，选择性Avpr 1b激动剂诱导CA 2的兴奋性突触反应显着增强，但在CA 1或Avpr 1b基因敲除小鼠的切片。Avpr 1b激动剂诱导的CA 2突触增强作用在机制上与催产素诱导的突触增强作用非常相似，依赖于NMDA受体激活、钙和钙/钙调蛋白依赖性蛋白激酶II活性，但不依赖于cAMP依赖性蛋白激酶活性或突触前机制。我们的数据表明，海马CA 2是重要的攻击响应男性入侵者和Avpr 1b，可能通过其在调节CA 2突触可塑性的作用，是一个必要的调解人。
The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator.