TMEM16B (ANO2) is the Ca2+-activated chloride channel expressed in multiple brain regions, including the amygdala. Here we report that Ano2 knockout mice exhibit impaired anxiety-related behaviors and context-independent fear memory, thus implicating TMEM16B in anxiety modulation. We found that TMEM16B is expressed in somatostatin-positive (SOM+) GABAergic neurons of the central lateral amygdala (CeL), and its activity modulates action potential duration and inhibitory postsynaptic current (IPSC). We further provide evidence for TMEM16B actions not only in the soma but also in the presynaptic nerve terminals of GABAergic neurons. Our study reveals an intriguing role for TMEM16B in context-independent but not context-dependent fear memory, and supports the notion that dysfunction of the amygdala contributes to anxiety-related behaviors.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Lily Yeh Jan
- Mu He
- Yuh Nung Jan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: The use and care of the mice complied with the guidelines of the Institutional Animal Care and Use Committee of UCSF (IACUC protocol AN181236), in accordance with the US National Institute of Health guidelines.
- Lisa M Monteggia, Vanderbilt University, United States
© 2019, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.
Background: Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) or local field potential recordings (LFP) can be used to extend neuroanatomical information (defined by magnetic resonance imaging) with neurophysiological activity patterns recorded from micro- and macroelectrodes probing the surgical target site. Currently, these two sources of information (imaging vs. electrophysiology) are analyzed separately, while means to fuse both data streams have not been introduced.
Methods: Here we present a tool that integrates resources from stereotactic planning, neuroimaging, MER and high-resolution atlas data to create a real-time visualization of the implant trajectory. We validate the tool based on a retrospective cohort of DBS patients (𝑁 = 52) offline and present single use cases of the real-time platform. Results: We establish an open-source software tool for multimodal data visualization and analysis during DBS surgery. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present examples that demonstrate the functionality of the tool.
Conclusions: This novel software platform for multimodal data visualization and analysis bears translational potential to improve accuracy of DBS surgery. The toolbox is made openly available and is extendable to integrate with additional software packages.
Funding: Deutsche Forschungsgesellschaft (410169619, 424778381), Deutsches Zentrum für Luftund Raumfahrt (DynaSti), National Institutes of Health (2R01 MH113929), Foundation for OCD Research (FFOR).