In vivo photoacoustic neuronal imaging of odor-evoked calcium signals in the drosophila brain (Conference Presentation)

Author(s):  
Ruiying Zhang ◽  
Bin Rao ◽  
Haoyang Rong ◽  
Baranidharan Raman ◽  
Lihong V. Wang
2021 ◽  
Author(s):  
Alex A. Legaria ◽  
Julia A. Licholai ◽  
Alexxai V. Kravitz

AbstractFiber photometry recordings are commonly used as a proxy for neuronal activity, based on the assumption that increases in bulk calcium fluorescence reflect increases in spiking of the underlying neural population. However, this assumption has not been adequately tested. Here, using endoscopic calcium imaging in the striatum we report that the bulk fluorescence signal correlates weakly with somatic calcium signals, suggesting that this signal does not reflect spiking activity, but may instead reflect subthreshold changes in neuropil calcium. Consistent with this suggestion, the bulk fluorescence photometry signal correlated strongly with neuropil calcium signals extracted from these same endoscopic recordings. We further confirmed that photometry did not reflect striatal spiking activity with simultaneous in vivo extracellular electrophysiology and fiber photometry recordings in awake behaving mice. We conclude that the fiber photometry signal should not be considered a proxy for spiking activity in neural populations in the striatum.Significance statementFiber photometry is a technique for recording brain activity that has gained popularity in recent years due to it being an efficient and robust way to record the activity of genetically defined populations of neurons. However, it remains unclear what cellular events are reflected in the photometry signal. While it is often assumed that the photometry signal reflects changes in spiking of the underlying cell population, this has not been adequately tested. Here, we processed calcium imaging recordings to extract both somatic and non-somatic components of the imaging field, as well as a photometry signal from the whole field. Surprisingly, we found that the photometry signal correlated much more strongly with the non-somatic than the somatic signals. This suggests that the photometry signal most strongly reflects subthreshold changes in calcium, and not spiking. We confirmed this point with simultaneous fiber photometry and extracellular spiking recordings, again finding that photometry signals relate poorly to spiking in the striatum. Our results may change interpretations of studies that use fiber photometry as an index of spiking output of neural populations.


2019 ◽  
Author(s):  
Mariam Ordyan ◽  
Tom Bartol ◽  
Mary Kennedy ◽  
Padmini Rangamani ◽  
Terrence Sejnowski

AbstractCalmodulin-dependent kinase II (CaMKII) has long been known to play an important role in learning and memory as well as long term potentiation (LTP). More recently it has been suggested that it might be involved in the time averaging of synaptic signals, which can then lead to the high precision of information stored at a single synapse. However, the role of the scaffolding molecule, neurogranin (Ng), in governing the dynamics of CaMKII is not yet fully understood. In this work, we adopt a rule-based modeling approach through the Monte Carlo method to study the effect of Ca2+ signals on the dynamics of CaMKII phosphorylation in the postsynaptic density (PSD). Calcium surges are observed in synaptic spines during an EPSP and back-propagating action potential due to the opening of NMDA receptors and voltage dependent calcium channels. We study the differences between the dynamics of phosphorylation of CaMKII monomers and dodecameric holoenzymes. The scaffolding molecule Ng, when present in significant concentration, limits the availability of free calmodulin (CaM), the protein which activates CaMKII in the presence of calcium. We show that it plays an important modulatory role in CaMKII phosphorylation following a surge of high calcium concentration. We find a non-intuitive dependence of this effect on CaM concentration that results from the different affinities of CaM for CaMKII depending on the number of calcium ions bound to the former. It has been shown previously that in the absence of phosphatase CaMKII monomers integrate over Ca2+ signals of certain frequencies through autophosphorylation (Pepke et al, Plos Comp. Bio., 2010). We also study the effect of multiple calcium spikes on CaMKII holoenzyme autophosphorylation, and show that in the presence of phosphatase CaMKII behaves as a leaky integrator of calcium signals, a result that has been recently observed in vivo. Our models predict that the parameters of this leaky integrator are finely tuned through the interactions of Ng, CaM, CaMKII, and PP1. This is a possible mechanism to precisely control the sensitivity of synapses to calcium signals.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Armelle Bohineust ◽  
Zacarias Garcia ◽  
Béatrice Corre ◽  
Fabrice Lemaître ◽  
Philippe Bousso
Keyword(s):  
T Cells ◽  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Chaim Glück ◽  
Kim David Ferrari ◽  
Noemi Binini ◽  
Annika Keller ◽  
Aiman S Saab ◽  
...  

Pericytes have been implicated in various neuropathologies, yet, little is known about their function and signaling pathways in health. Here, we characterized calcium dynamics of cortical mural cells in anesthetized or awake Pdgfrb-CreERT2;Rosa26 mice and in acute brain slices. Smooth muscle cells (SMCs) and ensheathing pericytes (EPs), also named as terminal vascular SMCs, revealed similar calcium dynamics in vivo. In contrast, calcium signals in capillary pericytes (CPs) were irregular, higher in frequency and occurred in cellular microdomains. In the absence of the vessel constricting agent U46619 in acute slices, SMCs and EPs revealed only sparse calcium signals whereas CPs retained their spontaneous calcium activity. Interestingly, chemogenetic activation of neurons in vivo and acute elevations of extracellular potassium in brain slices strongly decreased calcium activity in CPs. We propose that neuronal activation and an extracellular increase in potassium suppress calcium activity in CPs, likely mediated by Kir2.2 and KATP channels.


2020 ◽  
Author(s):  
Sergio Hidalgo ◽  
Nicolás Fuenzalida‐Uribe ◽  
Daniela Molina‐Mateo ◽  
Angélica P. Escobar ◽  
Carlos Oliva ◽  
...  

2020 ◽  
Vol 4 (s1) ◽  
pp. 11-11
Author(s):  
Tyler Nguyen ◽  
Zoe Vriesman ◽  
Peter Andrews ◽  
Sehban Masood ◽  
M Stewart ◽  
...  

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.


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