Youngstrom Isaac A, Strowbridge Ben W
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106.
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106
J Neurosci. 2015 Jun 10;35(23):8758-67. doi: 10.1523/JNEUROSCI.0311-15.2015.
Although the firing patterns of principal neurons in the olfactory bulb are known to be modulated strongly by respiration even under basal conditions, less is known about whether inhibitory local circuit activity in the olfactory bulb (OB) is modulated phasically. The diverse phase preferences of principal neurons in the OB and olfactory cortex that innervate granule cells (GCs) may interfere and prevent robust respiratory coupling, as suggested by recent findings. Using whole-cell recording, we examined the spontaneous, subthreshold membrane potential of GCs in the OBs of awake head-fixed mice. We found that, during periods of basal respiration, the synaptic input to GCs was strongly phase modulated, leading to a phase preference in the average, cycle-normalized membrane potential. Subthreshold phase tuning was heterogeneous in both mitral and tufted cells (MTCs) and GCs but relatively constant within each GC during periods of increased respiratory frequency. The timing of individual EPSPs in GC recordings also was phase modulated with the phase preference imparted by large-amplitude EPSPs, with fast kinetics often matching the phase tuning of the average membrane potential. These results suggest that activity in a subset of excitatory afferents to GCs, presumably including cortical feedback projections and other sources of large-amplitude unitary EPSPs, function to provide a timing signal linked to respiration. The phase preference we find in the membrane potential may provide a mechanism to dynamically modulate recurrent and lateral dendrodendritic inhibition of MTCs and to selective engage a subpopulation of interneurons based on the alignment of their phase tuning relative to sensory-driven MTC discharges.
尽管已知即使在基础条件下,嗅球中主要神经元的放电模式也会受到呼吸的强烈调节,但对于嗅球(OB)中抑制性局部回路活动是否受到相位调节却知之甚少。最近的研究结果表明,支配颗粒细胞(GCs)的OB和嗅觉皮层中主要神经元的不同相位偏好可能会相互干扰并阻止强大的呼吸耦合。我们使用全细胞记录法,研究了清醒的头部固定小鼠OB中GCs的自发亚阈值膜电位。我们发现,在基础呼吸期间,GCs的突触输入受到强烈的相位调制,导致平均的、经周期归一化的膜电位出现相位偏好。在呼吸频率增加期间,二尖瓣细胞和簇状细胞(MTCs)以及GCs中的亚阈值相位调谐是异质性的,但在每个GC内相对恒定。GC记录中单个兴奋性突触后电位(EPSPs)的时间也受到相位调制,其相位偏好由大幅度EPSPs赋予,快速动力学通常与平均膜电位的相位调谐相匹配。这些结果表明,GCs兴奋性传入神经元子集中的活动,可能包括皮层反馈投射和其他大幅度单一EPSPs来源,起到提供与呼吸相关的定时信号的作用。我们在膜电位中发现的相位偏好可能提供一种机制,来动态调节MTCs的反复和侧向树突-树突抑制,并根据其相位调谐与感觉驱动的MTC放电的对齐情况,选择性地激活一个中间神经元亚群。