期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 28, 页码 7407-7414出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3065-15.2016
关键词
awake behaving animals; chronic activity measurements; red-shifted Ca2+ indicator imaging; two-photon imaging
资金
- European Molecular Biology Organization (EMBO) Young Investigator Program
- Novartis Foundation
- Swiss National Science Foundation (SNSF) Consolidator Program
- SNSF [31003A-156943, 310030-127091]
- SNSF Sinergia Project [CRSII3_147660/1]
- EMBO long-term fellowship
- Swiss National Science Foundation (SNF) [CRSII3_147660, 31003A_156943, 310030_127091] Funding Source: Swiss National Science Foundation (SNF)
The hippocampal dentate gyrus is critically involved in learning and memory. However, methods for imaging the activity of its principal neurons, the dentate gyrus granule cells, are missing. Here we demonstrate chronic two-photon imaging of granule cell population activity in awake mice using a cortical window implant that leaves the hippocampal formation intact and does not lead to obvious alteration of animal behavior. Using virus delivery, we targeted expression of genetically encoded calcium indicators specifically to dentate gyrus granule cells. Calcium imaging of granule cell activity 600-800 mu m below the hippocampal surface was facilitated by using 1040 nm excitation of the red indicator R-CaMP1.07, but was also achieved using the green indicator GCaMP6s. We found that the rate of calcium transients was increased during wakefulness relative to an extremely low rate during anesthesia; however, activity still remained sparse with, on average, approximately one event per 2-5 min per cell across the granule cell population. Comparing periods of running on a ladder wheel and periods of resting, we furthermore identified state-dependent differences in the active granule cell population, with some cells displaying highest activity level during running and others during resting. Typically, cells did not maintain a clear state preference in their activity pattern across days. Our approach opens new avenues to elucidate granule cell function, plasticity mechanisms, and network computation in the adult dentate gyrus.
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