Department of Otolaryngology, Pittsburgh Hearing Research Center, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cereb Cortex. 2020 Jun 1;30(7):3895-3909. doi: 10.1093/cercor/bhaa005.
Cortical inhibition is essential for brain activity and behavior. Yet, the mechanisms that modulate cortical inhibition and their impact on sensory processing remain less understood. Synaptically released zinc, a neuromodulator released by cortical glutamatergic synaptic vesicles, has emerged as a powerful modulator of sensory processing and behavior. Despite the puzzling finding that the vesicular zinc transporter (ZnT3) mRNA is expressed in cortical inhibitory interneurons, the actions of synaptic zinc in cortical inhibitory neurotransmission remain unknown. Using in vitro electrophysiology and optogenetics in mouse brain slices containing the layer 2/3 (L2/3) of auditory cortex, we discovered that synaptic zinc increases the quantal size of inhibitory GABAergic neurotransmission mediated by somatostatin (SOM)- but not parvalbumin (PV)-expressing neurons. Using two-photon imaging in awake mice, we showed that synaptic zinc is required for the effects of SOM- but not PV-mediated inhibition on frequency tuning of principal neurons. Thus, cell-specific zinc modulation of cortical inhibition regulates frequency tuning.
皮质抑制对于大脑活动和行为至关重要。然而，调节皮质抑制的机制及其对感觉处理的影响仍知之甚少。突触释放的锌是一种由皮质谷氨酸能突触小泡释放的神经调质，它已成为调节感觉处理和行为的有力调节剂。尽管令人费解的是，囊泡锌转运体（ZnT3）mRNA 在皮质抑制性中间神经元中表达，但突触锌在皮质抑制性神经传递中的作用仍不清楚。我们使用包含听觉皮层第 2/3 层（L2/3）的体外脑片进行电生理学和光遗传学研究，发现突触锌增加了由生长抑素（SOM）表达神经元介导的抑制性 GABA 能神经传递的量子大小，但不增加由小清蛋白（PV）表达神经元介导的神经传递的量子大小。我们使用清醒小鼠的双光子成像，表明突触锌对于 SOM 而不是 PV 介导的抑制对主神经元频率调谐的影响是必需的。因此，皮质抑制的细胞特异性锌调节调节频率调谐。
