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Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f
GCaMP6f is among the most widely used genetically encoded calcium indicators for monitoring neuronal activity. Applications are at both the cellular and population levels. Here, we explore two important and under-explored issues. First, we have tested if GCaMP6f is sensitive enough for the detection...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593119/ https://www.ncbi.nlm.nih.gov/pubmed/31275115 http://dx.doi.org/10.3389/fncel.2019.00274 |
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author | Li, Pinggan Geng, Xinling Jiang, Huiyi Caccavano, Adam Vicini, Stefano Wu, Jian-young |
author_facet | Li, Pinggan Geng, Xinling Jiang, Huiyi Caccavano, Adam Vicini, Stefano Wu, Jian-young |
author_sort | Li, Pinggan |
collection | PubMed |
description | GCaMP6f is among the most widely used genetically encoded calcium indicators for monitoring neuronal activity. Applications are at both the cellular and population levels. Here, we explore two important and under-explored issues. First, we have tested if GCaMP6f is sensitive enough for the detection of population activity with sparse firing, similar to the sensitivity of the local field potential (LFP). Second, we have tested if GCaMP6f is fast enough for the detection of fast network oscillations critical for the encoding and consolidation of memory. We have focused this study on the activity of the hippocampal network including sharp waves (SWs), carbachol-induced theta oscillations, and interictal-like spikes. We compare simultaneous LFP and optical GCaMP6f fluorescent recordings in Thy1-GCaMP6f mouse hippocampal slices. We observe that SWs produce a clear population GCaMP6f signal above noise with an average magnitude of 0.3% ΔF/F. This population signal is highly correlated with the LFP, albeit with a delay of 40.3 ms (SD 10.8 ms). The population GCaMP6f signal follows the LFP evoked by 20 Hz stimulation with high fidelity, while electrically evoked oscillations up to 40 Hz were detectable with reduced amplitude. GCaMP6f and LFP signals showed a large amplitude discrepancy. The amplitude of GCaMP6f fluorescence increased by a factor of 28.9 (SD 13.5) between spontaneous SWs and carbachol-induced theta bursts, while the LFP amplitude increased by a factor of 2.4 (SD 1.0). Our results suggest that GCaMP6f is a useful tool for applications commonly considered beyond the scope of genetically encoded calcium indicators. In particular, population GCaMP6f signals are sensitive enough for detecting synchronous network events with sparse firing and sub-threshold activity, as well as asynchronous events with only a nominal LFP. In addition, population GCaMP6f signals are fast enough for monitoring theta and beta oscillations (<25 Hz). Faster calcium indicators (e.g., GCaMP7) will further improve the frequency response for the detection of gamma band oscillations. The advantage of population optical over LFP recordings are that they are non-contact and free from stimulation artifacts. These features may be particularly useful for high-throughput recordings and applications sensitive to stimulus artifact, such as monitoring responses during continuous stimulation. |
format | Online Article Text |
id | pubmed-6593119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65931192019-07-03 Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f Li, Pinggan Geng, Xinling Jiang, Huiyi Caccavano, Adam Vicini, Stefano Wu, Jian-young Front Cell Neurosci Neuroscience GCaMP6f is among the most widely used genetically encoded calcium indicators for monitoring neuronal activity. Applications are at both the cellular and population levels. Here, we explore two important and under-explored issues. First, we have tested if GCaMP6f is sensitive enough for the detection of population activity with sparse firing, similar to the sensitivity of the local field potential (LFP). Second, we have tested if GCaMP6f is fast enough for the detection of fast network oscillations critical for the encoding and consolidation of memory. We have focused this study on the activity of the hippocampal network including sharp waves (SWs), carbachol-induced theta oscillations, and interictal-like spikes. We compare simultaneous LFP and optical GCaMP6f fluorescent recordings in Thy1-GCaMP6f mouse hippocampal slices. We observe that SWs produce a clear population GCaMP6f signal above noise with an average magnitude of 0.3% ΔF/F. This population signal is highly correlated with the LFP, albeit with a delay of 40.3 ms (SD 10.8 ms). The population GCaMP6f signal follows the LFP evoked by 20 Hz stimulation with high fidelity, while electrically evoked oscillations up to 40 Hz were detectable with reduced amplitude. GCaMP6f and LFP signals showed a large amplitude discrepancy. The amplitude of GCaMP6f fluorescence increased by a factor of 28.9 (SD 13.5) between spontaneous SWs and carbachol-induced theta bursts, while the LFP amplitude increased by a factor of 2.4 (SD 1.0). Our results suggest that GCaMP6f is a useful tool for applications commonly considered beyond the scope of genetically encoded calcium indicators. In particular, population GCaMP6f signals are sensitive enough for detecting synchronous network events with sparse firing and sub-threshold activity, as well as asynchronous events with only a nominal LFP. In addition, population GCaMP6f signals are fast enough for monitoring theta and beta oscillations (<25 Hz). Faster calcium indicators (e.g., GCaMP7) will further improve the frequency response for the detection of gamma band oscillations. The advantage of population optical over LFP recordings are that they are non-contact and free from stimulation artifacts. These features may be particularly useful for high-throughput recordings and applications sensitive to stimulus artifact, such as monitoring responses during continuous stimulation. Frontiers Media S.A. 2019-06-19 /pmc/articles/PMC6593119/ /pubmed/31275115 http://dx.doi.org/10.3389/fncel.2019.00274 Text en Copyright © 2019 Li, Geng, Jiang, Caccavano, Vicini and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Li, Pinggan Geng, Xinling Jiang, Huiyi Caccavano, Adam Vicini, Stefano Wu, Jian-young Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title | Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title_full | Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title_fullStr | Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title_full_unstemmed | Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title_short | Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f |
title_sort | measuring sharp waves and oscillatory population activity with the genetically encoded calcium indicator gcamp6f |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593119/ https://www.ncbi.nlm.nih.gov/pubmed/31275115 http://dx.doi.org/10.3389/fncel.2019.00274 |
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