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2559 Janelia Publications

Showing 71-80 of 2559 results
06/02/24 | Dynamic assemblies of parvalbumin interneurons in brain oscillations.
Huang Y, Chen H, Lin Y, Lin S, Zheng Q, Abdelfattah AS, Lavis LD, Schreiter ER, Lin B, Chen T
Neuron. 2024 Jun 02:. doi: 10.1016/j.neuron.2024.05.015

Brain oscillations are crucial for perception, memory, and behavior. Parvalbumin-expressing (PV) interneurons are critical for these oscillations, but their population dynamics remain unclear. Using voltage imaging, we simultaneously recorded membrane potentials in up to 26 PV interneurons in vivo during hippocampal ripple oscillations in mice. We found that PV cells generate ripple-frequency rhythms by forming highly dynamic cell assemblies. These assemblies exhibit rapid and significant changes from cycle to cycle, varying greatly in both size and membership. Importantly, this variability is not just random spiking failures of individual neurons. Rather, the activities of other PV cells contain significant information about whether a PV cell spikes or not in a given cycle. This coordination persists without network oscillations, and it exists in subthreshold potentials even when the cells are not spiking. Dynamic assemblies of interneurons may provide a new mechanism to modulate postsynaptic dynamics and impact cognitive functions flexibly and rapidly.

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06/28/24 | Exploration and exploitation are flexibly balanced during local search in flies
Goldschmidt D, Guo Y, Chitnis SS, Christoforou C, Turner-Evans D, Ribeiro C, Hermundstad AM, Jayaraman V, Haberkern H
bioRxiv. 2024 Jun 28:. doi: 10.1101/2024.06.26.600764

After finding food, a foraging animal must decide whether to continue feeding, or to explore the environment for potentially better options. One strategy to negotiate this tradeoff is to perform local searches around the food but repeatedly return to feed. We studied this behavior in flies and used genetic tools to uncover the underlying mechanisms. Over time, flies gradually expand their search, shifting from primarily exploiting food sources to exploring the environment, a change that is likely driven by increases in satiety. We found that flies’ search patterns preserve these dynamics even as the overall scale of the search is modulated by starvation-induced changes in metabolic state. In contrast, search induced by optogenetic activation of sugar sensing neurons does not show these dynamics. We asked what navigational strategies underlie local search. Using a generative model, we found that a change in locomotor pattern after food consumption could account for repeated returns to the food, but failed to capture relatively direct, long return trajectories. Alternative strategies, such as path integration or sensory taxis could allow flies to return from larger distances. We tested this by individually silencing the fly’s head direction system, olfaction and hygrosensation, and found that the only substantial effect was from perturbing hygrosensation, which reduced the number of long exploratory trips. Our study illustrates that local search is composed of multiple behavioral features that evolve over time based on both internal and external factors, providing a path towards uncovering the underlying neural mechanisms.

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06/01/24 | Resolution in super-resolution microscopy - definition, trade-offs and perspectives.
Prakash K, Baddeley D, Eggeling C, Fiolka R, Heintzmann R, Manley S, Radenovic A, Smith C, Shroff H, Schermelleh L
Nat Rev Mol Cell Biol. 2024 Jul 01:. doi: 10.1038/s41580-024-00755-7

Super-resolution microscopy (SRM) is gaining popularity in biosciences; however, claims about optical resolution are contested and often misleading. In this Viewpoint, experts share their views on resolution and common trade-offs, such as labelling and post-processing, aiming to clarify them for biologists and facilitate deeper understanding and best use of SRM.

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07/02/24 | Towards a simplified model of primary visual cortex
Du F, Núñez-Ochoa MA, Pachitariu M, Stringer C
bioRxiv. 2024 Jul 02:. doi: 10.1101/2024.06.30.601394

Artificial neural networks (ANNs) have been shown to predict neural responses in primary visual cortex (V1) better than classical models. However, this performance comes at the expense of simplicity because the ANN models typically have many hidden layers with many feature maps in each layer. Here we show that ANN models of V1 can be substantially simplified while retaining high predictive power. To demonstrate this, we first recorded a new dataset of over 29,000 neurons responding to up to 65,000 natural image presentations in mouse V1. We found that ANN models required only two convolutional layers for good performance, with a relatively small first layer. We further found that we could make the second layer small without loss of performance, by fitting a separate "minimodel" to each neuron. Similar simplifications applied for models of monkey V1 neurons. We show that these relatively simple models can nonetheless be useful for tasks such as object and visual texture recognition and we use the models to gain insight into how texture invariance arises in biological neurons.

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06/25/24 | Near-infrared nanosensors enable optical imaging of oxytocin with selectivity over vasopressin in acute mouse brain slices.
Mun J, Navarro N, Jeong S, Ouassil N, Leem E, Beyene AG, Landry MP
Proc Natl Acad Sci U S A. 2024 Jun 25;121(26):e2314795121. doi: 10.1073/pnas.2314795121

Oxytocin plays a critical role in regulating social behaviors, yet our understanding of its function in both neurological health and disease remains incomplete. Real-time oxytocin imaging probes with spatiotemporal resolution relevant to its endogenous signaling are required to fully elucidate oxytocin's role in the brain. Herein, we describe a near-infrared oxytocin nanosensor (nIROXT), a synthetic probe capable of imaging oxytocin in the brain without interference from its structural analogue, vasopressin. nIROXT leverages the inherent tissue-transparent fluorescence of single-walled carbon nanotubes (SWCNT) and the molecular recognition capacity of an oxytocin receptor peptide fragment to selectively and reversibly image oxytocin. We employ these nanosensors to monitor electrically stimulated oxytocin release in brain tissue, revealing oxytocin release sites with a median size of 3 µm in the paraventricular nucleus of C57BL/6 mice, which putatively represents the spatial diffusion of oxytocin from its point of release. These data demonstrate that covalent SWCNT constructs, such as nIROXT, are powerful optical tools that can be leveraged to measure neuropeptide release in brain tissue.

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06/20/24 | Neocortical inhibitory imbalance predicts successful sensory detection.
Deister CA, Moore AI, Voigts J, Bechek S, Lichtin R, Brown TC, Moore CI
Cell Rep. 2024 Jun 20;43(7):114233. doi: 10.1016/j.celrep.2024.114233

Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection. In primary somatosensory and visual neocortex, a distinct PYR subset shows increased rate and spike-count correlations on detected trials ("hits"), while most show no rate change and decreased correlations. A larger fraction of FS/PVs predicts hits with either rate increases or decreases. Using computational modeling, we found that inhibitory imbalance, created by excitatory "feedback" and interactions between FS/PV pools, can account for the data. Rate-decreasing FS/PVs increase rate and correlation in a PYR subset, while rate-increasing FS/PVs reduce correlations and offset enhanced excitation in PYR neurons. These findings indicate that selection of informative PYR ensembles, through transient inhibitory imbalance, is a common motif of optimal neocortical processing.

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06/25/24 | Hot-Distance: Combining One-Hot and Signed Distance Embeddings for Segmentation
Marwan Zouinkhi , Jeff L. Rhoades , Aubrey V. Weigel
arXiv. 2024 Jun 25:2406.17936. doi: 10.48550/arXiv.2406.17936

Machine learning models are only as good as the data to which they are fit. As such, it is always preferable to use as much data as possible in training models. What data can be used for fitting a model depends a lot on the formulation of the task. We introduce Hot-Distance, a novel segmentation target that incorporates the strength of signed boundary distance prediction with the flexibility of one-hot encoding, to increase the amount of usable training data for segmentation of subcellular structures in focused ion beam scanning electron microscopy (FIB-SEM).

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06/17/24 | Steering From the Rear: Coordination of Central Pattern Generators Underlying Navigation by Ascending Interneurons
Jonaitis J, Hibbard KL, Layte KM, Hiramoto A, Cardona A, Truman JW, Nose A, Zwart MF, Pulver SR
bioRxiv. 2024 Jun 17:. doi: 10.1101/2024.06.17.598162

Understanding how animals coordinate movements to achieve goals is a fundamental pursuit in neuroscience. Here we explore how neurons that reside in posterior lower-order regions of a locomotor system and project to anterior higher-order regions influence steering and navigation. We characterized the anatomy and functional role of a population of ascending interneurons in the ventral nerve cord of Drosophila larvae. Through electron microscopy reconstructions and light microscopy, we determined that the cholinergic 19f cells receive input primarily from premotor interneurons and synapse upon a diverse array of postsynaptic targets within the anterior segments including other 19f cells. Calcium imaging of 19f activity in isolated CNS preparations in relation to motor neurons revealed that 19f neurons are recruited into most larval motor programmes. 19f activity lags behind motor neuron activity and as a population, the cells encode spatio-temporal patterns of locomotor activity in the larval CNS. Optogenetic manipulations of 19f cell activity in isolated CNS preparations revealed that they coordinate the activity of central pattern generators underlying exploratory headsweeps and forward locomotion in a context and location specific manner. In behaving animals, activating 19f cells suppressed exploratory headsweeps and slowed forward locomotion, while inhibition of 19f activity potentiated headsweeps, slowing forward movement. Inhibiting activity in 19f cells ultimately affected the ability of larvae to remain in the vicinity of an odor source during an olfactory navigation task. Overall, our findings provide insights into how ascending interneurons monitor motor activity and shape interactions amongst rhythm generators underlying complex navigational tasks.

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05/31/24 | Salivary gland developmental mechanics
Morales EA, Wang S
Current Topics in Developmental Biology:. doi: 10.1016/bs.ctdb.2024.05.002

The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical ductal system. The expansive epithelial surface generated by branching morphogenesis serves as the structural basis for the efficient production and delivery of saliva. Here, we elucidate the process of salivary gland morphogenesis, emphasizing the role of mechanics. Structurally, the developing salivary gland is characterized by a stratified epithelium tightly encased by the basement membrane, which is in turn surrounded by a mesenchyme consisting of a dense network of interstitial matrix and mesenchymal cells. Diverse cell types and extracellular matrices bestow this developing organ with organized, yet spatially varied mechanical properties. For instance, the surface epithelial sheet of the bud is highly fluidic due to its high cell motility and weak cell-cell adhesion, rendering it highly pliable. In contrast, the inner core of the bud is more rigid, characterized by reduced cell motility and strong cell-cell adhesion, which likely provide structural support for the tissue. The interactions between the surface epithelial sheet and the inner core give rise to budding morphogenesis. Furthermore, the basement membrane and the mesenchyme offer mechanical constraints that could play a pivotal role in determining the higher-order architecture of a fully mature salivary gland.

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06/10/24 | Phase diversity-based wavefront sensing for fluorescence microscopy.
Johnson C, Guo M, Schneider MC, Su Y, Khuon S, Reiser N, Wu Y, Riviere PL, Shroff H
Optica. 2024 Jun 10;11(6):806-820. doi: 10.1364/OPTICA.518559

Fluorescence microscopy is an invaluable tool in biology, yet its performance is compromised when the wavefront of light is distorted due to optical imperfections or the refractile nature of the sample. Such optical aberrations can dramatically lower the information content of images by degrading image contrast, resolution, and signal. Adaptive optics (AO) methods can sense and subsequently cancel the aberrated wavefront, but are too complex, inefficient, slow, or expensive for routine adoption by most labs. Here we introduce a rapid, sensitive, and robust wavefront sensing scheme based on phase diversity, a method successfully deployed in astronomy but underused in microscopy. Our method enables accurate wavefront sensing to less than λ/35 root mean square (RMS) error with few measurements, and AO with no additional hardware besides a corrective element. After validating the method with simulations, we demonstrate calibration of a deformable mirror > 100-fold faster than comparable methods (corresponding to wavefront sensing on the ~100 ms scale), and sensing and subsequent correction of severe aberrations (RMS wavefront distortion exceeding λ/2), restoring diffraction-limited imaging on extended biological samples.

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