Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing.
Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing.
复制标题
DOI：
10.1073/pnas.2113313119
复制
发表时间：
2022-01-25
影响因子：
11.1
通讯作者：
Kim SG
中科院分区：
文献类型：
--
作者：
Jung WB;Jiang H;Lee S;Kim SG
功能性磁共振成像（fMRI）通过允许响应于各种刺激的功能区域的非侵入性映射和静息状态功能连接的非侵入性映射，导致了脑科学的巨大进步。诱发和静息态功能网络都包含多个大脑区域，这些区域在层次上是相互连接的。因此，确定不同回路对fMRI结果的相对贡献对于更好地理解大脑功能和静息态连接至关重要。在这里，我们采用了局部沉默与光遗传学刺激抑制下游网络，并成功地解剖功能磁共振成像反应在电路水平。这种功能磁共振成像方法为理解全脑的、基于人群的神经回路开辟了一条途径，允许研究个体动物中由神经病理学改变和学习引起的功能重组。为了进一步推进基于功能磁共振成像（fMRI）的脑科学，在电路水平上剖析fMRI活动至关重要。为了实现这一目标，我们将全脑功能磁共振成像与明确区域的神经元沉默相结合。由于局灶性失活抑制了向下游通路的兴奋性输出，因此可以将完整的输入回路和受抑制的输出回路分开。采用光遗传学方法刺激小鼠躯体感觉区GABA能神经元，进行高特异性脑血容量加权fMRI。全脑自发的躯体感觉网络主要存在于同侧皮层和皮层下区域，这与静息状态下功能磁共振成像数据中常见的双侧同伦连接不同。诱发的功能磁共振成像反应的体感刺激的区域的体感网络被成功地解剖，允许脊髓丘脑（ST），丘脑皮质（TC），皮质丘脑（CT），皮质皮质（CC）的输入，并确定局部皮质内电路的相对贡献。丘脑腹后核接收ST输入，而丘脑后内侧核接收来自初级体感皮层（S1）的CT输入和TC输入。次级躯体感觉皮层（S2）主要接受来自S1的直接CC输入和来自腹后外侧核的少量TC输入。皮层区域的TC和CC输入层通过半峰全宽<150 µm的椎板特异性fMRI反应来识别。长距离的突触输入在皮层区域放大约两倍的本地皮层内电路，这是一致的电生理记录。总的来说，具有光遗传失活的全脑功能磁共振成像显示了全脑范围的、基于人群的、长距离的电路，这可以补充传统显微功能电路研究中通常收集的数据。
Functional MRI (fMRI) has led to tremendous advancements in brain science by allowing noninvasive mapping of functional regions in response to various stimuli and noninvasive mapping of resting-state functional connectivity. Both evoked and resting-state functional networks contain multiple brain regions that are hierarchically yet reciprocally connected. Therefore, it is critical to determine the relative contributions of different circuits to fMRI findings to better understand brain functions and resting-state connectivity. Here, we adopted local silencing with optogenetic stimulation to suppress downstream networks and successfully dissected fMRI responses at the circuit level. This fMRI approach opens an avenue for understanding brain-wide, population-based neural circuits, allowing investigations of functional reorganization caused by neuropathological modifications and learning in individual animals. To further advance functional MRI (fMRI)–based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume–weighted fMRI was performed with optogenetic stimulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs, and local intracortical circuits to be determined. The ventral posterior thalamic nucleus receives ST inputs, while the posterior medial thalamic nucleus receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the ventral posterolateral nucleus. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half maximum of <150 µm. Long-range synaptic inputs in cortical areas were amplified approximately twofold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based, long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.
登录
查看更多内容
高分辨率fMRI的时间依赖性空间特异性：对介质神经血管耦合的见解。
DOI：
10.1098/rstb.2019.0623
发表时间：
2021-01-04
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Fukuda M;Poplawsky AJ;Kim SG
通讯作者：
Kim SG
影响因子：
64.8
作者：
Harris JA;Mihalas S;Hirokawa KE;Whitesell JD;Choi H;Bernard A;Bohn P;Caldejon S;Casal L;Cho A;Feiner A;Feng D;Gaudreault N;Gerfen CR;Graddis N;Groblewski PA;Henry AM;Ho A;Howard R;Knox JE;Kuan L;Kuang X;Lecoq J;Lesnar P;Li Y;Luviano J;McConoughey S;Mortrud MT;Naeemi M;Ng L;Oh SW;Ouellette B;Shen E;Sorensen SA;Wakeman W;Wang Q;Wang Y;Williford A;Phillips JW;Jones AR;Koch C;Zeng H
通讯作者：
Zeng H
影响因子：
48
作者：
Ayling, Oliver G. S.;Harrison, Thomas C.;Murphy, Timothy H.
通讯作者：
Murphy, Timothy H.
影响因子：
5.7
作者：
Jin, Tao;Kim, Seong-Gi
通讯作者：
Kim, Seong-Gi
影响因子：
16.2
作者：
Ferezou, Isabelle;Haiss, Florent;Petersen, Carl C. H.
通讯作者：
Petersen, Carl C. H.