Frequency-Tuned Distribution of Inhibition in the Dentate Gyrus
Frequency-Tuned Distribution of Inhibition in the Dentate Gyrus
复制标题
DOI：
10.1523/jneurosci.1854-10.2010
复制
发表时间：
2010-09-22
影响因子：
5.3
通讯作者：
Jones, Mathew V.
中科院分区：
文献类型：
--
作者：
Ewell, Laura A.;Jones, Mathew V.
齿状回的颗粒细胞（GCs）使用稀疏编码来执行冗余减少、模式分离和新颖性检测。加强低尖峰活动的一个可能的候选机制是前馈抑制，其中来自穿孔路径（PP）的皮质兴奋驱动招募gaba能中间神经元，然后抑制GCs。然而，关于PP驱动是如何在GCs和抑制性神经元之间平衡的，我们知之甚少。在C57BL/6小鼠的GCs和快速尖峰（FS）中间神经元的同时记录中，我们发现局灶性PP刺激比GCs更优先地激发FS中间神经元的尖峰，因为GCs需要更大的兴奋性突触电流密度才能达到尖峰阈值。阻断抑制逆转了这一关系，揭示了PP和GC与FS中间神经元之间更强的内在耦合，并表明抑制可以通过严格调节GC尖峰概率使齿状回的输出稀疏化。此外，这种调节是动态的，因为FS中间神经元的尖峰谱是频率调谐的，在接近θ节奏频率（类似于10 Hz）的PP刺激下表现出爆发行为。脉冲中较晚的尖峰是反馈抑制通路的一部分，因为它们是由晚期epsc驱动的，被GC突触输出的抑制剂阻断，并且与GC尖峰具有相同的频率依赖性。因此，通过PP到达的信号的时间内容决定了FS中间神经元是否只参与前馈（一个尖峰）或前馈和反馈（脉冲）抑制。
Granule cells (GCs) of the dentate gyrus use sparse encoding to perform redundancy reduction, pattern separation, and novelty detection. One likely candidate mechanism to enforce low spiking activity is feedforward inhibition, in which the cortical excitatory drive from the perforant path (PP) recruits GABAergic interneurons that then inhibit GCs. Little is known, however, about how PP drive is balanced between GCs versus inhibitory neurons. In simultaneous recordings of GCs and fast-spiking (FS) interneurons from C57BL/6 mice, we find that focal PP stimulation preferentially recruits spiking in FS interneurons over GCs, because GCs require a larger excitatory synaptic current density to reach spike threshold. Blocking inhibition reversed this relationship, revealing a stronger intrinsic coupling between the PP and GCs versus FS interneurons and showing that inhibition can sparsify the output of the dentate gyrus by tightly regulating GC spike probability. Moreover, this regulation is dynamic, because the spiking profile of FS interneurons was frequency tuned, displaying bursting behavior in response to PP stimulation near theta rhythm frequency (similar to 10 Hz). The later spikes in the bursts were part of the feedback inhibitory pathway because they were driven by late EPSCs, were blocked by an inhibitor of synaptic output from GCs, and shared the same frequency dependence as GC spiking. Therefore, the temporal content of signals arriving via the PP determines whether a FS interneuron participates in only feedforward (one spike) or both feedforward and feedback (burst) inhibition.