Neuroscience Program, Vanderbilt University, Nashville, Tennessee 37235.
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235.
J Neurosci. 2022 Apr 6;42(14):2917-2929. doi: 10.1523/JNEUROSCI.1604-21.2022. Epub 2022 Feb 23.
Working memory ability continues to mature into adulthood in humans and nonhuman primates. At the single-neuron level, adolescent development is characterized by increased prefrontal firing rate in the delay period, but less is known about how coordinated activity between neurons is altered. Local field potentials (LFPs) provide a window into the computations conducted by the local network. To address the effects of adolescent development on LFP activity, three male rhesus monkeys were trained to perform an oculomotor delayed response task and tested at both the adolescent and adult stages. Simultaneous single-unit and LFP signals were recorded from areas 8a and 46 of the dorsolateral prefrontal cortex. In both the cue and delay period, power relative to baseline in the gamma frequency range (32-128 Hz) was higher in the adolescent than the adult stage. The changes between developmental stages could not be accounted for by differences in performance and were observed in more posterior as well as more anterior recording sites. In the adult stage, high-firing neurons were also more likely to reside at sites with strong gamma power increase from baseline. For both stages, the gamma power increase in the delay was selective for sites with neuron-encoding stimulus information in their spiking. Our results establish gamma power decrease to be a feature of prefrontal cortical maturation. Gamma-frequency oscillations in extracellular field recordings (e.g., local field potential or EEG) are a marker of normal interactions between excitatory and inhibitory neurons in neural circuits. Abnormally low gamma power during working memory is seen in conditions such as schizophrenia. We sought to examine whether the immature prefrontal cortex similarly exhibits lower power in the gamma-frequency range during working memory, in a nonhuman primate model of adolescence. Contrary to this expectation, the adolescent PFC exhibited stronger gamma power during the maintenance of working memory. Our findings reveal an unknown developmental maturation trajectory of gamma-band oscillations, propose a refinement of information encoding during PFC maturation, and raise the possibility that schizophrenia represents an excessive state of prefrontal maturation.
工作记忆能力在人类和非人类灵长类动物中持续成熟到成年期。在单细胞水平上，青少年发育的特征是在延迟期前额叶发射率增加，但神经元之间协调活动的变化知之甚少。局部场电位（LFPs）为局部网络进行的计算提供了一个窗口。为了研究青少年发育对 LFP 活动的影响，三只雄性恒河猴接受了眼动延迟反应任务的训练，并在青少年和成年阶段进行了测试。同时从背外侧前额叶皮层的 8a 和 46 区记录单个单元和 LFP 信号。在提示和延迟期，相对于基线的伽马频带（32-128 Hz）的功率在青少年期比成年期更高。发育阶段之间的变化不能用表现的差异来解释，并且在更后和更前的记录部位也观察到了这种变化。在成年阶段，高发射神经元也更有可能位于基线伽马功率增加较强的部位。对于两个阶段，延迟期的伽马功率增加是针对其尖峰中具有神经元编码刺激信息的部位选择性的。我们的结果确立了伽马功率下降是前额叶皮质成熟的一个特征。细胞外场记录（例如，局部场电位或 EEG）中的伽马频带振荡是神经网络中兴奋性和抑制性神经元正常相互作用的标志。在精神分裂症等情况下，工作记忆中的异常低伽马功率可见。我们试图检查青春期非人类灵长类动物模型中，不成熟的前额叶皮质在工作记忆过程中是否同样表现出较低的伽马频带功率。与这一预期相反，青少年 PFC 在工作记忆的维持过程中表现出更强的伽马功率。我们的发现揭示了伽马频带振荡的未知发育成熟轨迹，提出了 PFC 成熟过程中信息编码的改进，并提出了精神分裂症代表前额叶成熟过度状态的可能性。
