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3836 Publications

Showing 81-90 of 3836 results
11/22/23 | ACC neural ensemble dynamics are structured by strategy prevalence
Mikhail Proskurin , Maxim Manakov , Alla Y. Karpova
eLife. 2023 Nov 22:. doi: 10.7554/eLife.84897

Medial frontal cortical areas are thought to play a critical role in the brain's ability to flexibly deploy strategies that are effective in complex settings. Still, the specific circuit computations that underpin this foundational aspect of intelligence remain unclear. Here, by examining neural ensemble activity in rats that sample different strategies in a self-guided search for latent task structure, we demonstrate a robust tracking of individual strategy prevalence in the anterior cingulate cortex (ACC), especially in an area homologous to primate area 32D. Prevalence encoding in the ACC is wide-scale, independent of reward delivery, and persists through a substantial ensemble reorganization that tags ACC representations with contextual content. Our findings argue that ACC ensemble dynamics is structured by a summary statistic of recent behavioral choices, raising the possibility that ACC plays a role in estimating - through statistical learning - which actions promote the occurrence of events in the environment.

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11/21/23 | Distributed representations of innate behaviors in the hypothalamus do not predict specialized functional centers.
Stefanos Stagkourakis , Giada Spigolon , Markus Marks , Michael Feyder , Joseph Kim , Pietro Perona , Marius Pachitariu , David J. Anderson
bioRxiv. 2023 Nov 21:. doi: 10.1101/2023.11.21.568163

Survival behaviors are orchestrated by hardwired circuits located in deep subcortical brain regions, most prominently the hypothalamus. Artificial activation of spatially localized, genetically defined hypothalamic cell populations is known to trigger distinct behaviors, suggesting a nucleus-centered organization of behavioral control. However, no study has investigated the hypothalamic representation of innate behaviors using unbiased, large-scale single neuron recordings. Here, using custom silicon probes, we performed recordings across the rostro-caudal extent of the medial hypothalamus in freely moving animals engaged in a diverse array of social and predator defense (“fear”) behaviors. Nucleus-averaged activity revealed spatially distributed generic “ignition signals” that occurred at the onset of each behavior, and did not identify sparse, nucleus-specific behavioral representations. Single-unit analysis revealed that social and fear behavior classes are encoded by activity in distinct sets of spatially distributed neuronal ensembles spanning the entire hypothalamic rostro-caudal axis. Individual ensemble membership, however, was drawn from neurons in 3-4 adjacent nuclei. Mixed selectivity was identified as the most prevalent mode of behavior representation by individual hypothalamic neurons. Encoding models indicated that a significant fraction of the variance in single neuron activity is explained by behavior. This work reveals that innate behaviors are encoded in the hypothalamus by activity in spatially distributed neural ensembles that each span multiple neighboring nuclei, complementing the prevailing view of hypothalamic behavioral control by single nucleus-restricted cell types derived from perturbational studies.

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11/20/23 | All-optical reporting of inhibitory receptor driving force in the nervous system.
Joshua S. Selfe , Teresa J. S. Steyn , Eran F. Shorer , Richard J. Burman , Kira M. Düsterwald , Ahmed S. Abdelfattah , Eric R. Schreiter , Sarah E. Newey , Colin J. Akerman , Joseph V. Raimondo
bioRxiv. 2023 Nov 20:. doi: 10.1101/2023.08.30.555464

Ionic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, and are a fundamental property of all cells. In the brain for example, fast synaptic inhibition is mediated by chloride permeable GABAA receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DFGABAA). Here we present a new tool for quantifying inhibitory receptor driving force named ORCHID: all-Optical Reporting of CHloride Ion Driving force. We demonstrate ORCHID’s ability to provide accurate, high-throughput measurements of resting and dynamic DFGABAA from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about the biophysical mechanisms that establish DFGABAA, reveals novel differences in DFGABAA between neurons and astrocytes, and affords the first in vivo measurements of intact DFGABAA. This work extends our understanding of inhibitory synaptic transmission and establishes a precedent for all-optical methods to assess ionic driving forces.

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11/20/23 | Facemap: a framework for modeling neural activity based on orofacial tracking
Atika Syeda , Lin Zhong , Renee Tung , Will Long , Marius Pachitariu , Carsen Stringer
Nature Neuroscience. 2023 Nov 20:. doi: 10.1038/s41593-023-01490-6

Recent studies in mice have shown that orofacial behaviors drive a large fraction of neural activity across the brain. To understand the nature and function of these signals, we need better computational models to characterize the behaviors and relate them to neural activity. Here we developed Facemap, a framework consisting of a keypoint tracking algorithm and a deep neural network encoder for predicting neural activity. We used the Facemap keypoints as input for the deep neural network to predict the activity of ∼50,000 simultaneously-recorded neurons and in visual cortex we doubled the amount of explained variance compared to previous methods. Our keypoint tracking algorithm was more accurate than existing pose estimation tools, while the inference speed was several times faster, making it a powerful tool for closed-loop behavioral experiments. The Facemap tracker was easy to adapt to data from new labs, requiring as few as 10 annotated frames for near-optimal performance. We used Facemap to find that the neuronal activity clusters which were highly driven by behaviors were more spatially spread-out across cortex. We also found that the deep keypoint features inferred by the model had time-asymmetrical state dynamics that were not apparent in the raw keypoint data. In summary, Facemap provides a stepping stone towards understanding the function of the brainwide neural signals and their relation to behavior.

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11/13/23 | Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment.
Daugird TA, Shi Y, Holland KL, Rostamian H, Liu Z, Lavis LD, Rodriguez J, Strahl BD, Legant WR
bioRxiv. 2023 Nov 13:. doi: 10.1101/2023.11.09.566470

In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we developed an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrated that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacted nucleosome diffusive properties in a manner that was dependent on local chromatin density and supportive of a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Our results reveal that nuclear heterogeneity arises from both active and passive process and highlights the need to account for different organizational principals when modeling different chromatin environments.

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11/13/23 | High-fidelity 3D live-cell nanoscopy through data-driven enhanced super-resolution radial fluctuation.
Laine RF, Heil HS, Coelho S, Nixon-Abell J, Jimenez A, Wiesner T, Martínez D, Galgani T, Régnier L, Stubb A, Follain G, Webster S, Goyette J, Dauphin A, Salles A, Culley S, Jacquemet G, Hajj B, Leterrier C, Henriques R
Nature Methods. 2023 Nov 13:. doi: 10.1038/s41592-023-02057-w

Live-cell super-resolution microscopy enables the imaging of biological structure dynamics below the diffraction limit. Here we present enhanced super-resolution radial fluctuations (eSRRF), substantially improving image fidelity and resolution compared to the original SRRF method. eSRRF incorporates automated parameter optimization based on the data itself, giving insight into the trade-off between resolution and fidelity. We demonstrate eSRRF across a range of imaging modalities and biological systems. Notably, we extend eSRRF to three dimensions by combining it with multifocus microscopy. This realizes live-cell volumetric super-resolution imaging with an acquisition speed of ~1 volume per second. eSRRF provides an accessible super-resolution approach, maximizing information extraction across varied experimental conditions while minimizing artifacts. Its optimal parameter prediction strategy is generalizable, moving toward unbiased and optimized analyses in super-resolution microscopy.

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11/08/23 | Preserved neural dynamics across animals performing similar behaviour.
Safaie M, Chang JC, Park J, Miller LE, Dudman JT, Perich MG, Gallego JA
Nature. 2023 Nov 08:. doi: 10.1038/s41586-023-06714-0

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals because of their common evolutionarily specified developmental programme. Such organization at the circuit level may constrain neural activity, leading to low-dimensional latent dynamics across the neural population. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.

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11/06/23 | A complete reconstruction of the early visual system of an adult insect.
Chua NJ, Makarova AA, Gunn P, Villani S, Cohen B, Thasin M, Wu J, Shefter D, Pang S, Xu CS, Hess HF, Polilov AA, Chklovskii DB
Current Biology. 2023 Nov 06;33(21):4611-4623. doi: 10.1016/j.cub.2023.09.021

For most model organisms in neuroscience, research into visual processing in the brain is difficult because of a lack of high-resolution maps that capture complex neuronal circuitry. The microinsect Megaphragma viggianii, because of its small size and non-trivial behavior, provides a unique opportunity for tractable whole-organism connectomics. We image its whole head using serial electron microscopy. We reconstruct its compound eye and analyze the optical properties of the ommatidia as well as the connectome of the first visual neuropil-the lamina. Compared with the fruit fly and the honeybee, Megaphragma visual system is highly simplified: it has 29 ommatidia per eye and 6 lamina neuron types. We report features that are both stereotypical among most ommatidia and specialized to some. By identifying the "barebones" circuits critical for flying insects, our results will facilitate constructing computational models of visual processing in insects.

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11/03/23 | Volitional activation of remote place representations with a hippocampal brain-machine interface.
Lai C, Tanaka S, Harris TD, Lee AK
Science. 2023 Nov 03;382(6670):566-573. doi: 10.1126/science.adh5206

The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including maplike representations of familiar environments. However, whether representations in such "cognitive maps" can be volitionally accessed is unknown. We developed a brain-machine interface to test whether rats can do so by controlling their hippocampal activity in a flexible, goal-directed, and model-based manner. We found that rats can efficiently navigate or direct objects to arbitrary goal locations within a virtual reality arena solely by activating and sustaining appropriate hippocampal representations of remote places. This provides insight into the mechanisms underlying episodic memory recall, mental simulation and planning, and imagination and opens up possibilities for high-level neural prosthetics that use hippocampal representations.

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11/01/23 | Nanometer-scale views of visual cortex reveal anatomical features of primary cilia poised to detect synaptic spillover
Carolyn M Ott , Russel Torres , Tung-Sheng Kuan , Aaron T Kuan , JoAnn Buchanan , Leila Elabbady , Sharmishtaa Seshamani , Agnes L Bodor , Forrest C Collman , Davi D Bock , Wei-Chung Allen Lee , Nuno Macarico da Costa , Jennifer Lippincott-Schwartz
bioRxiv. 2023 Nov 01:. doi: 10.1101/2023.10.31.564838

A primary cilium is a thin membrane-bound extension off a cell surface that contains receptors for perceiving and transmitting signals that modulate cell state and activity. While many cell types have a primary cilium, little is known about primary cilia in the brain, where they are less accessible than cilia on cultured cells or epithelial tissues and protrude from cell bodies into a deep, dense network of glial and neuronal processes. Here, we investigated cilia frequency, internal structure, shape, and position in large, high-resolution transmission electron microscopy volumes of mouse primary visual cortex. Cilia extended from the cell bodies of nearly all excitatory and inhibitory neurons, astrocytes, and oligodendrocyte precursor cells (OPCs), but were absent from oligodendrocytes and microglia. Structural comparisons revealed that the membrane structure at the base of the cilium and the microtubule organization differed between neurons and glia. OPC cilia were distinct in that they were the shortest and contained pervasive internal vesicles only occasionally observed in neuron and astrocyte cilia. Investigating cilia-proximal features revealed that many cilia were directly adjacent to synapses, suggesting cilia are well poised to encounter locally released signaling molecules. The internal anatomy, including microtubule changes and centriole location, defined key structural features including cilium placement and shape. Together, the anatomical insights both within and around neuron and glia cilia provide new insights into cilia formation and function across cell types in the brain.

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