A whole-brain map of long-range inputs to GABAergic interneurons in the mouse medial prefrontal cortex

Sun, Qingtao; Li, Xiangning; Ren, Miao; Zhao, Mengting; Zhong, Qiuyuan; Ren, Yuqi; Luo, Pan; Hóng, Ní; Zhang, Xiaoyu; Zhang, Chen; Yuan, Jing; Li, Anan; Luo, Minmin; Gong, Hui; Luo, Qi

doi:10.1038/s41593-019-0429-9

Cited by 156 publications

(124 citation statements)

References 58 publications

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“…an essential component of motivation). The present study took the advantage of optogenetics, which can selectively manipulate pathways and thereby enabled us to distinguish the AM from other ATh nuclei because the AM, but not the other ATh nuclei, sends efferents to and receive afferents from the mPFC 38,40,41 . We found that response-contingent stimulation of mPFC-to-AM, AM, and AM-to-mPFC neurons triggered ICSS.…”

Section: Discussionmentioning

confidence: 99%

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

Yang

Talishinsky

et al. 2020

Preprint

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How does the prefrontal cortex (PFC) regulate motivated behavior? Our experiments characterize the circuits of the PFC regulating motivation, reinforcement and dopamine activity, revealing a novel cortico-thalamic loop. The stimulation of medial PFC (mPFC) neurons activated many downstream regions, as shown by functional MRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. Reciprocal excitatory functional connectivity, as well as co-activation of the two regions, was found in human participants who watched reinforcing videos. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement and dopaminergic neuron activity.

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Section: Discussionmentioning

confidence: 99%

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

Yang

Talishinsky

et al. 2020

Preprint

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“…in visual cortex in response to a focal seizure triggered in somatosensory cortex (Wenzel et al, 2017;Liou et al, 2018). Anatomically, the effect may be contributed by long-distance, cross-areal projections that preferentially project to inhibitory interneurons in their target circuits (Zhang et al, 2014;Sun et al, 2019). In addition, focal seizures may depress brain-wide activities via disrupting subcortical structures (Feng et al, 2017) and ascending activation systems (Blumenfeld, 2012).…”

Section: Discussionmentioning

confidence: 99%

A theoretical model for focal seizure initiation, propagation, termination, and progression

Liou

et al. 2019

Preprint

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We developed a neural network model that can account for the major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus and postulates a role for synaptic plasticity in emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure evolution end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this can provide a roadmap and potentially a testbed for future explorations of seizure mechanisms and clinical therapies.

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“…Despite this variance, the global agreement suggests that our computationally inexpensive matrix inversion method faithfully reproduces cell counts across the whole brain. Figure 3a shows the optimal MISS results for Pv+, Sst+, and Vip+ interneurons side-by-side with corresponding maps produced using viral labeling 23 . Although these viral-labeled maps only include interneurons with monosynaptic inputs from the prelimbic (green) and infralimbic (red) areas, there is very strong visual agreement between experimental and MISS-inferred maps (Figure 3a).…”

Section: Mrx3 Provides the Best Overall Performance Among Subsetting mentioning

confidence: 99%

Matrix Inversion and Subset Selection (MISS): A novel pipeline for mapping of diverse cell types across the murine brain

Mezias

Torok

Maia

et al. 2019

Preprint

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The advent of increasingly sophisticated imaging platforms has allowed for the visualization of the murine nervous system at single-cell resolution. However, current cell counting methods compromise on either the ability to map a large number of different cell types, or spatial coverage, and therefore whole-brain quantification of finely resolved neural cell subtypes remains elusive. Here we present a comprehensive and novel computational pipeline called Matrix Inversion and Subset Selection (MISS) that aims to fill this gap in knowledge and has the ability to infer counts of diverse collections of neural cell types at sub-millimeter resolution using a combination of single-cell RNAseq and in situ hybridization datasets. We rigorously demonstrate the accuracy of MISS against literature expectations, and in so doing, provide the first verified maps for twenty-five distinct neuronal and nonneuronal cell types across the whole mouse brain. The resulting comprehensive cell type maps are uniquely suited to address important open questions in neuroscience. As a demonstration, we utilize our inferred maps to quantitatively establish that adult cell type distributions reflect the ontological splits between brain regions during neural development, indicating that the developmental history of brain regions informs their final cell-type composition. Although this link has been frequently surmised by neuroscientists, its quantitative verification across the entire brain has not previously been demonstrated. Together, our results suggest that the MISS pipeline can be used to generate accurate spatial quantification of diverse cell types without the direct imaging of known type-specific markers, as has been done previously. The entire MISS pipeline and outputs will be made open source in order to catalyze future neuroscientific advances across disciplines.

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A whole-brain map of long-range inputs to GABAergic interneurons in the mouse medial prefrontal cortex

Cited by 156 publications

References 58 publications

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

A theoretical model for focal seizure initiation, propagation, termination, and progression

Matrix Inversion and Subset Selection (MISS): A novel pipeline for mapping of diverse cell types across the murine brain

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