Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
Learn Mem. 2010 Oct 29;17(11):582-90. doi: 10.1101/lm.1962010. Print 2010 Nov.
Synaptically released Zn²+ is a potential modulator of neurotransmission and synaptic plasticity in fear-conditioning pathways. Zinc transporter 3 (ZnT3) knock-out (KO) mice are well suited to test the role of zinc in learned fear, because ZnT3 is colocalized with synaptic zinc, responsible for its transport to synaptic vesicles, highly enriched in the amygdala-associated neural circuitry, and ZnT3 KO mice lack Zn²+ in synaptic vesicles. However, earlier work reported no deficiency in fear memory in ZnT3 KO mice, which is surprising based on the effects of Zn²+ on amygdala synaptic plasticity. We therefore reexamined ZnT3 KO mice in various tasks for learned and innate fear. The mutants were deficient in a weak fear-conditioning protocol using single tone-shock pairing but showed normal memory when a stronger, five-pairing protocol was used. ZnT3 KO mice were deficient in memory when a tone was presented as complex auditory information in a discontinuous fashion. Moreover, ZnT3 KO mice showed abnormality in trace fear conditioning and in fear extinction. By contrast, ZnT3 KO mice had normal anxiety. Thus, ZnT3 is involved in associative fear memory and extinction, but not in innate fear, consistent with the role of synaptic zinc in amygdala synaptic plasticity.
突触释放的 Zn²+ 是恐惧条件反射途径中神经递质传递和突触可塑性的潜在调节剂。锌转运蛋白 3（ZnT3）敲除（KO）小鼠非常适合测试锌在学习恐惧中的作用，因为 ZnT3 与突触锌共定位，负责将其转运到突触小泡中，而突触小泡在杏仁核相关神经回路中高度富集，ZnT3 KO 小鼠缺乏突触小泡中的 Zn²+。然而，早期的工作报道 ZnT3 KO 小鼠在恐惧记忆中没有缺陷，这与 Zn²+ 对杏仁核突触可塑性的影响相矛盾。因此，我们在各种学习和先天恐惧任务中重新检查了 ZnT3 KO 小鼠。这些突变体在使用单一音波配对的弱恐惧条件反射协议中表现出缺陷，但在使用更强的五对配对协议时表现出正常的记忆。当以不连续的方式呈现作为复杂听觉信息的音波时，ZnT3 KO 小鼠的记忆会出现缺陷。此外，ZnT3 KO 小鼠在痕迹恐惧条件反射和恐惧消退中表现出异常。相比之下，ZnT3 KO 小鼠的焦虑正常。因此，ZnT3 参与了联想性恐惧记忆和消退，但不参与先天恐惧，这与突触锌在杏仁核突触可塑性中的作用一致。
