Kotak Vibhakar C, Fujisawa Sho, Lee Fanyee Anja, Karthikeyan Omkar, Aoki Chiye, Sanes Dan H
Center for Neural Science, New York University, New York, New York 10003, USA.
J Neurosci. 2005 Apr 13;25(15):3908-18. doi: 10.1523/JNEUROSCI.5169-04.2005.
Developmental hearing impairments compromise sound discrimination, speech acquisition, and cognitive function; however, the adjustments of functional properties in the primary auditory cortex (A1) remain unknown. We induced sensorineural hearing loss (SNHL) in developing gerbils and then reared the animals for several days. The intrinsic membrane and synaptic properties of layer 2/3 pyramidal neurons were subsequently examined in a thalamocortical brain slice preparation with whole-cell recordings and electron microscopic immunocytochemistry. SNHL neurons displayed a depolarized resting membrane potential, an increased input resistance, and a higher incidence of sustained firing. They also exhibited significantly larger thalamocortically and intracortically evoked excitatory synaptic responses, including a greater susceptibility to the NMDA receptor antagonist AP-5 and the NR2B subunit antagonist ifenprodil. This correlated with an increase in NR2B labeling of asymmetric synapses, as visualized ultrastructurally. Furthermore, decreased frequency and increased amplitude of miniature EPSCs (mEPSCs) in SNHL neurons suggest that a decline in presynaptic release properties is compensated by an increased excitatory response. To verify that the increased thalamocortical excitation was elicited by putative monosynaptic connections, minimum amplitude ventral medial geniculate nucleus-evoked EPSCs were recorded. These minimum-evoked responses were of larger amplitude, and the NMDAergic currents were also larger and longer in SNHL neurons. These findings were supported by significantly longer AP-5-sensitive durations and larger amplitudes of mEPSCs. Last, the amplitudes of intracortically evoked monosynaptic and polysynaptic GABAergic inhibitory synaptic responses were significantly smaller in SNHL neurons. These alterations in cellular properties after deafness reflect an attempt by A1 to sustain an operative level of cortical excitability that may involve homeostatic mechanisms.
发育性听力障碍会损害声音辨别、语言习得和认知功能；然而，初级听觉皮层（A1）功能特性的调整仍不清楚。我们在发育中的沙鼠中诱导感音神经性听力损失（SNHL），然后将动物饲养几天。随后，在丘脑皮质脑片标本中，通过全细胞记录和电子显微镜免疫细胞化学技术，研究了2/3层锥体神经元的内在膜特性和突触特性。SNHL神经元表现出静息膜电位去极化、输入电阻增加和持续放电发生率更高。它们还表现出丘脑皮质和皮质内诱发的兴奋性突触反应显著增大，包括对NMDA受体拮抗剂AP-5和NR2B亚基拮抗剂艾芬地尔的敏感性增加。这与超微结构观察到的不对称突触中NR2B标记增加相关。此外，SNHL神经元中微小兴奋性突触后电流（mEPSCs）的频率降低和幅度增加表明，突触前释放特性的下降通过兴奋性反应的增加得到补偿。为了验证丘脑皮质兴奋性增加是由假定的单突触连接引起的，记录了最小幅度腹内侧膝状体核诱发的EPSCs。这些最小诱发反应的幅度更大，SNHL神经元中的NMDA能电流也更大且持续时间更长。这些发现得到了mEPSCs的AP-5敏感持续时间显著延长和幅度更大的支持。最后，SNHL神经元中皮质内诱发的单突触和多突触GABA能抑制性突触反应的幅度显著较小。耳聋后细胞特性的这些改变反映了A1试图维持皮质兴奋性的有效水平，这可能涉及稳态机制。
