Russo Simone, Dimwamwa Elaida D, Stanley Garrett B
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
J Neurosci. 2025 Sep 9. doi: 10.1523/JNEUROSCI.0094-25.2025.
Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation reflect the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice (both male and female) expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway in awake, head-fixed mice, we presented ramp-and-hold light at different intensities while recording neural activity in the primary somatosensory barrel cortex (S1) and the ventral posteromedial nucleus (VPm) of the thalamus using silicon probes. We found that the activation of S1 L6CT neurons induces high-frequency LFP oscillations in S1 that are modulated in frequency, but not in amplitude, across light intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the temporal evolution of firing rate in S1 and VPm. While most S1 neurons were steadily suppressed, VPm and S1 Layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to facilitated within 500 ms, suggesting differential recruitment of the intracortical vs cortico-thalamo-cortical pathways. Finally, we found that LFP frequency selectively correlates with VPm firing rate. Taken together, our data suggests that L6CT neurons sculpt the frequency of S1 LFP oscillations through cortico-thalamo-cortical circuits, linking the recurrent interactions mediated by L6CT neurons to the high gamma oscillations observed across physiological and pathological conditions. Layer 6 corticothalamic (L6CT) neurons are strategically positioned to modulate the cortex and the thalamus allowing them to engage distinct, yet interlocked, circuits. Here we show that the activation of L6CT neurons in the mouse primary somatosensory cortex induces fast cortical oscillations through the coordinated engagement of cortico-thalamo-cortical and intracortical pathways. Our work reveals that these two L6CT-mediated pathways exert competing effects: while intracortical connections suppress cortical spiking, the activity of the cortico-thalamo-cortical loop rapidly evolves, facilitating cortical spiking. We demonstrate that the cortico-thalamo-cortical pathway operates on a faster timescale than the intracortical pathway and critically shapes cortical oscillation frequency. These findings reveal how the unique position of corticothalamic neurons allows them to flexibly and dynamically modulate the thalamocortical network.
第6层皮质丘脑（L6CT）神经元投射到皮质和丘脑，产生多种效应，包括调节皮质和丘脑的放电，以及在皮质局部场电位（LFP）中出现高频伽马振荡。我们假设由L6CT神经元激活驱动的高频伽马振荡反映了皮质内和皮质-丘脑-皮质回路的动态参与。为了验证这一点，我们通过光遗传学方法激活了NTSR1-cre小鼠（雄性和雌性）中L6CT神经元表达通道视紫红质-2的L6CT神经元。利用清醒、头部固定小鼠的触须通路，我们在不同强度下呈现斜坡-保持光，同时使用硅探针记录初级体感桶状皮质（S1）和丘脑腹后内侧核（VPm）的神经活动。我们发现，S1区L6CT神经元的激活在S1区诱发高频LFP振荡，其频率在不同光强度和不同时间内受到调制，但幅度不受影响。为了确定哪些神经元类别对这些振荡有贡献，我们研究了S1区和VPm区放电率的时间演变。虽然大多数S1神经元被稳定抑制，但VPm区和S1区第4层快速放电（L4 FS）神经元在500毫秒内从被抑制转变为易化，这表明皮质内与皮质-丘脑-皮质通路的募集存在差异。最后，我们发现LFP频率与VPm区放电率选择性相关。综上所述，我们的数据表明，L6CT神经元通过皮质-丘脑-皮质回路塑造S1区LFP振荡的频率，将L6CT神经元介导的反复相互作用与在生理和病理条件下观察到的高频伽马振荡联系起来。第6层皮质丘脑（L6CT）神经元处于战略位置，可调节皮质和丘脑，使其能够参与不同但相互关联的回路。在这里，我们表明，小鼠初级体感皮质中L6CT神经元的激活通过皮质-丘脑-皮质和皮质内通路的协同参与诱发快速皮质振荡。我们的研究揭示，这两条由L6CT介导的通路发挥着相互竞争的作用：虽然皮质内连接抑制皮质放电，但皮质-丘脑-皮质环路的活动迅速演变，促进皮质放电。我们证明，皮质-丘脑-皮质通路的运行时间尺度比皮质内通路更快，并且对皮质振荡频率起着关键的塑造作用。这些发现揭示了皮质丘脑神经元的独特位置如何使其能够灵活、动态地调节丘脑皮质网络。
