scholarly journals Automated cellular structure extraction in biological images with applications to calcium imaging data

2018 ◽  
Author(s):  
Gal Mishne ◽  
Ronald R. Coifman ◽  
Maria Lavzin ◽  
Jackie Schiller

AbstractRecent advances in experimental methods in neuroscience enable measuring in-vivo activity of large populations of neurons at cellular level resolution. To leverage the full potential of these complex datasets and analyze the dynamics of individual neurons, it is essential to extract high-resolution regions of interest, while addressing demixing of overlapping spatial components and denoising of the temporal signal of each neuron. In this paper, we propose a data-driven solution to these challenges, by representing the spatiotemporal volume as a graph in the image plane. Based on the spectral embedding of this graph calculated across trials, we propose a new clustering method, Local Selective Spectral Clustering, capable of handling overlapping clusters and disregarding clutter. We also present a new nonlinear mapping which recovers the structural map of the neurons and dendrites, and global video denoising. We demonstrate our approach on in-vivo calcium imaging of neurons and apical dendrites, automatically extracting complex structures in the image domain, and denoising and demixing their time-traces.

2021 ◽  
Author(s):  
Hannah S Wirtshafter ◽  
John F Disterhoft

Calcium imaging using GCaMP calcium indicators and miniature microscopes has been used to image cellular populations during long timescales and in different task phases, as well as to determine neuronal circuit topology and organization. Because the hippocampus (HPC) is essential for many tasks of memory, spatial navigation, and learning, calcium imaging of large populations of HPC neurons can provide new insight on cell changes and organization over time during these tasks. To our knowledge, all reported HPC in vivo calcium imaging experiments have been done in mouse. However, rats have many behavioral and physiological experimental advantages over mice, and, due to their larger size, rats are able to support larger implants, thereby enabling the recording of a greater number of cells. In this paper, we present the first in vivo calcium imaging from CA1 hippocampus in freely moving rats. Using GCaMP7c and the UCLA Miniscope, we demonstrate that hundreds of cells (mean 240+-90 cells per session, maximum 428 cells) can reliably be visualized and held across weeks, and that calcium events in these cells are correlated with periods of movement. We additionally show proof of method by showing that an extremely high percent of place cells (82.3%+-8.1%, far surpassing the percent seen during mouse calcium imaging) can be recorded on a navigational task, and that these place cells enable accurately decoding of animal position. Finally, we show that calcium imaging is rats is not prone to photobleaching during hour-long recordings and that cells can be reliably recorded for an hour or more per session. A detailed protocol for this technique, including notes on the numerous parameter changes needed to use Ca2+ in rats, is included in the Materials and Methods section, and implications of these advancements are discussed.


2019 ◽  
Author(s):  
Peter Ledochowitsch ◽  
Lawrence Huang ◽  
Ulf Knoblich ◽  
Michael Oliver ◽  
Jerome Lecoq ◽  
...  

AbstractMultiphoton calcium imaging is commonly used to monitor the spiking of large populations of neurons. Recovering action potentials from fluorescence necessitates calibration experiments, often with simultaneous imaging and cell-attached recording. Here we performed calibration for imaging conditions matching those of the Allen Brain Observatory. We developed a novel crowd-sourced, algorithmic approach to quality control. Our final data set was 50 recordings from 35 neurons in 3 mouse lines. Our calibration indicated that 3 or more spikes were required to produce consistent changes in fluorescence. Moreover, neither a simple linear model nor a more complex biophysical model accurately predicted fluorescence for small numbers of spikes (1-3). We observed increases in fluorescence corresponding to prolonged depolarizations, particularly in Emx1-IRES-Cre mouse line crosses. Our results indicate that deriving spike times from fluorescence measurements may be an intractable problem in some mouse lines.


2018 ◽  
Vol 84 (1) ◽  
pp. e51 ◽  
Author(s):  
Alexander D. Jacob ◽  
Adam I. Ramsaran ◽  
Andrew J. Mocle ◽  
Lina M. Tran ◽  
Chen Yan ◽  
...  

2022 ◽  
Vol 225 (1) ◽  
Author(s):  
Madeleine S. Junkins ◽  
Sviatoslav N. Bagriantsev ◽  
Elena O. Gracheva

ABSTRACT Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the physiological changes that occur during hibernation have been comprehensively researched, the role of the nervous system in this process remains relatively underexplored. In this Review, we adopt the perspective that the nervous system plays an active, essential role in facilitating and supporting hibernation. Accumulating evidence strongly suggests that the hypothalamus enters a quiescent state in which powerful drives to thermoregulate, eat and drink are suppressed. Similarly, cardiovascular and pulmonary reflexes originating in the brainstem are altered to permit the profoundly slow heart and breathing rates observed during torpor. The mechanisms underlying these changes to the hypothalamus and brainstem are not currently known, but several neuromodulatory systems have been implicated in the induction and maintenance of hibernation. The intersection of these findings with modern neuroscience approaches, such as optogenetics and in vivo calcium imaging, has opened several exciting avenues for hibernation research.


2019 ◽  
Vol 11 (522) ◽  
pp. eaaw6435 ◽  
Author(s):  
Boris D. Heifets ◽  
Juliana S. Salgado ◽  
Madison D. Taylor ◽  
Paul Hoerbelt ◽  
Daniel F. Cardozo Pinto ◽  
...  

The extensively abused recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA) has shown promise as an adjunct to psychotherapy for treatment-resistant psychiatric disease. It is unknown, however, whether the mechanisms underlying its prosocial therapeutic effects and abuse potential are distinct. We modeled both the prosocial and nonsocial drug reward of MDMA in mice and investigated the mechanism of these processes using brain region–specific pharmacology, transgenic manipulations, electrophysiology, and in vivo calcium imaging. We demonstrate in mice that MDMA acting at the serotonin transporter within the nucleus accumbens is necessary and sufficient for MDMA’s prosocial effect. MDMA’s acute rewarding properties, in contrast, require dopaminergic signaling. MDMA’s prosocial effect requires 5-HT1b receptor activation and is mimicked by d-fenfluramine, a selective serotonin-releasing compound. By dissociating the mechanisms of MDMA’s prosocial effects from its addictive properties, we provide evidence for a conserved neuronal pathway, which can be leveraged to develop novel therapeutics with limited abuse liability.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A2-A2
Author(s):  
C E Mahoney ◽  
W Zhao ◽  
A Coffey ◽  
C Woods ◽  
D Kroeger ◽  
...  

Abstract Introduction People with narcolepsy type 1 report that cataplexy is triggered most often by positive social experiences such as laughing with friends, yet the mechanisms through which social interaction promotes cataplexy are unknown. We hypothesize a subpopulation of central amygdala neurons that are sensitive to the prosocial neuropeptide, oxytocin (CeAOTR), respond to positive valence and trigger cataplexy. Methods We have used in vivo calcium imaging, chemogenetic and optogenetic approaches to characterize the activity pattern of these neurons and to manipulate their activity state. Results Cre-dependent anterograde tracing of the CeAOTR neurons of the central amygdala indicate a moderate to dense projection to the REM sleep-regulatory region of the ventral lateral periaqueductal gray (vlPAG). Additionally, Channel Rhodopsin Assisted Circuit Mapping (CRACM) experiments show that CeAOTR neurons inhibit vlPAG neurons that innervate the REM atonia-promoting region, the sublaterodorsal nucleus. Targeted photostimulation (15Hz (10ms) for 20sec every hour) of the CeAOTR fibers in the vlPAG doubled the amount of cataplexy. Preliminary in vivo calcium imaging indicates that the CeAOTR are active just prior to the onset of cataplexy. Chemogenetic and optogenetic activation of CeAOTR neurons increased cataplexy. Conclusion We conclude that the CeAOTR subpopulation is sufficient to promote cataplexy. Our future directions include determining the necessity of these oxytocin sensitive neurons in cataplexy under different conditions of positive valence. Support R01 NS106032 and WakeUp Narcolepsy.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Bocchio ◽  
Claire Gouny ◽  
David Angulo-Garcia ◽  
Tom Toulat ◽  
Thomas Tressard ◽  
...  

Abstract The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.


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