Activity-dependent LTP in the dentate gyrus promotes epileptic seizures

Epilepsy is a devastating brain disorder whose cellular mechanisms remain poorly understood. Excitatory mossy cells (MCs) in the dentate gyrus of the hippocampus are implicated in temporal lobe epilepsy, the most common form of focal epilepsy in adults. However, the role of MCs during initial seizures, before MC loss occurs, is unclear. Here, we show that initial seizures induced with kainic acid (KA) intraperitoneal injection in adult mice, a well-established model of experimental epilepsy, not only increased MC and granule cell (GC) activity in vivo, but also triggered a BDNF-dependent long-term potentiation at MC-GC synapses (MC-GC LTP). In vivo induction of MC-GC LTP worsened KA-induced seizures, whereas selective MC silencing and Bdnf genetic removal from GCs, which abolishes LTP, were both anti-epileptic. Thus, initial seizures strengthen MC-GC synaptic transmission, thereby promoting epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help develop therapeutic strategies for early intervention.</jats:p

Delayed formation of neural representations of space in aged mice

AbstractAging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for processing spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Usingin vivotwo-photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.</jats:p

Adult neurogenesis improves spatial information encoding in the mouse hippocampus - EE dataset

&lt;p&gt;&lt;strong&gt;In vivo two-photon imaging dataset for Frechou et al. "Adult neurogenesis improves spatial information encoding in the mouse hippocampus"&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This dataset includes data from mice that were housed in an enriched environment (EE).&nbsp;&lt;/p&gt; &lt;p&gt;For each recording we included raw imaging data consisting of:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Individual frames (.tif files) from 3 consecutive 3 min Ca2+ imaging movies (which were concatenated for analysis)&lt;/li&gt; &lt;li&gt;Microscope settings metadata (Experiment.xml)&lt;/li&gt; &lt;li&gt;Mouse location data (Episode001.h5 in SyncData folder) containing rotary encoder and RFID data&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Some analyzed data is also included:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Suite2p analysis data (&lt;strong&gt;Suite2p&lt;/strong&gt; folder)&lt;/li&gt; &lt;li&gt;&lt;strong&gt;fluorescence.npy&nbsp;&lt;/strong&gt;contains raw fluorescence data (the F output of Suite2p data extraction). Rows are individual cells and columns are frames (i.e. timepoints) acquired at 15.253 Hz.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;positions.npy&nbsp;&lt;/strong&gt;contains the position of the mouse on the treadmill belt indexed from 0 to 100.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Both NumPy(.npy) files are the output of the Preprocessing.py code, part of the analysis pipeline used for data analysis in the original publication, which can be found at &lt;a href="https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis"&gt;https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis&lt;/a&gt;&lt;/p&gt; &lt;p&gt;All imaged mice were female. Refer to the original publication for additional information.&nbsp;&lt;/p&gt;&lt;p&gt;We thank Dr. Jake Jordan, Roland Ferger, Elizabeth Wood, Dr. Maria Gulinello, Kevin Fisher, Dr. Mimi Kim and Dr. Sacha Sokoloski for technical advice, assistance and discussions. M.A.F. was supported by a Fulbright Scholarship. M.A.F. and K.D.M. were funded by The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. J.T.G. was supported by the Whitehall Foundation (Research Grant 2019-05-71) and the National Institutes of Health (NINDS R01NS125252-01A1). R.C.C. was supported by the National Institutes of Health (NEI R01EY030578, NIDA RF1DA056400). Confocal microscopy experiments were supported by a&nbsp; shared instrumentation grant (1S10OD025295-01A1). This article is dedicated to the memory of Dr. Paul S. Frenette (1965-2021) who provided invaluable encouragement and support for this project.&lt;/p&gt

Adult neurogenesis improves spatial information encoding in the mouse hippocampus - hM4Di Controls Part 2

&lt;p&gt;&lt;strong&gt;In vivo two-photon imaging dataset for Frechou et al. "Adult neurogenesis improves spatial information encoding in the mouse hippocampus"&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This dataset includes data from CNO-induced chemogenetic silencing experiments in hM4Di-(control) mice. There is another Zenodo dataset with the remaining hM4Di-(control) mice &lt;a href="https://doi.org/10.5281/zenodo.10913386"&gt;here&lt;/a&gt;. The folder for each mouse includes baseline (pre) and post-CNO (cno) recordings.&lt;/p&gt; &lt;p&gt;For each recording we included raw imaging data consisting of:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Individual frames (.tif files) from 3 consecutive 3 min Ca2+ imaging movies (which were concatenated for analysis)&lt;/li&gt; &lt;li&gt;Microscope settings metadata (Experiment.xml)&lt;/li&gt; &lt;li&gt;Mouse location data (Episode001.h5 in SyncData folder) containing rotary encoder and RFID data&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Some analyzed data is also included:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Suite2p analysis data (&lt;strong&gt;Suite2p&lt;/strong&gt; folder)&lt;/li&gt; &lt;li&gt;&lt;strong&gt;fluorescence.npy&nbsp;&lt;/strong&gt;contains raw fluorescence data (the F output of Suite2p data extraction). Rows are individual cells and columns are frames (i.e. timepoints) acquired at 15.253 Hz.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;positions.npy&nbsp;&lt;/strong&gt;contains the position of the mouse on the treadmill belt indexed from 0 to 100.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Both NumPy(.npy) files are the output of the Preprocessing.py code, part of the analysis pipeline used for data analysis in the original publication, which can be found at &lt;a href="https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis"&gt;https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis&lt;/a&gt;&lt;/p&gt; &lt;p&gt;Refer to the original publication for additional information. The sex of individual mice is as follows:&lt;/p&gt; &lt;table&gt; &lt;tbody&gt; &lt;tr&gt; &lt;td&gt;&lt;strong&gt;Group&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Mouse #&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Sex&lt;/strong&gt;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;hM4Di-&lt;/td&gt; &lt;td&gt;M4&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M5&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;/tbody&gt; &lt;/table&gt;&lt;p&gt;&lt;strong&gt;ACKNOWLEDGEMENTS&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We thank Dr. Jake Jordan, Roland Ferger, Elizabeth Wood, Dr. Maria Gulinello, Kevin Fisher, Dr. Mimi Kim and Dr. Sacha Sokoloski for technical advice, assistance and discussions. M.A.F. was supported by a Fulbright Scholarship. M.A.F. and K.D.M. were funded by The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. J.T.G. was supported by the Whitehall Foundation (Research Grant 2019-05-71) and the National Institutes of Health (NINDS R01NS125252-01A1). R.C.C. was supported by the National Institutes of Health (NEI R01EY030578, NIDA RF1DA056400). Confocal microscopy experiments were supported by a&nbsp; shared instrumentation grant (1S10OD025295-01A1). This article is dedicated to the memory of Dr. Paul S. Frenette (1965-2021) who provided invaluable encouragement and support for this project.&lt;/p&gt

Adult neurogenesis improves spatial information encoding in the mouse hippocampus - hM4Di Silencing

&lt;p&gt;&lt;strong&gt;In vivo two-photon imaging dataset for Frechou et al. "Adult neurogenesis improves spatial information encoding in the mouse hippocampus"&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This dataset includes data from CNO-induced chemogenetic silencing experiments in hM4Di+ and hM4Di-(control) mice. There is another Zenodo dataset with the remaining hM4Di-(control) mice &lt;a href="https://doi.org/10.5281/zenodo.10949624"&gt;here&lt;/a&gt;. The folder for each mouse includes baseline (pre) and post-CNO (cno) recordings.&lt;/p&gt; &lt;p&gt;For each recording we included raw imaging data consisting of:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Individual frames (.tif files) from 3 consecutive 3 min Ca2+ imaging movies (which were concatenated for analysis)&lt;/li&gt; &lt;li&gt;Microscope settings metadata (Experiment.xml)&lt;/li&gt; &lt;li&gt;Mouse location data (Episode001.h5 in SyncData folder) containing rotary encoder and RFID data&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Some analyzed data is also included:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Suite2p analysis data (&lt;strong&gt;Suite2p&lt;/strong&gt; folder)&lt;/li&gt; &lt;li&gt;&lt;strong&gt;fluorescence.npy&nbsp;&lt;/strong&gt;contains raw fluorescence data (the F output of Suite2p data extraction). Rows are individual cells and columns are frames (i.e. timepoints) acquired at 15.253 Hz.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;positions.npy&nbsp;&lt;/strong&gt;contains the position of the mouse on the treadmill belt indexed from 0 to 100.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Both NumPy(.npy) files are the output of the Preprocessing.py code, part of the analysis pipeline used for data analysis in the original publication, which can be found at &lt;a href="https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis"&gt;https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis&lt;/a&gt;&lt;/p&gt; &lt;p&gt;Refer to the original publication for additional information. The sex of individual mice is as follows:&lt;/p&gt; &lt;p&gt;&nbsp;&lt;/p&gt; &lt;table&gt; &lt;tbody&gt; &lt;tr&gt; &lt;td&gt;&lt;strong&gt;Group&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Mouse #&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Sex&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Group&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Mouse #&lt;/strong&gt;&lt;/td&gt; &lt;td&gt;&lt;strong&gt;Sex&lt;/strong&gt;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;hM4Di+&lt;/td&gt; &lt;td&gt;M1&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;td&gt;hM4Di-&lt;/td&gt; &lt;td&gt;M1&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M2&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M2&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M3&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M3&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M4&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M5&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M6&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M7&lt;/td&gt; &lt;td&gt;M&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M8&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;tr&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;M9&lt;/td&gt; &lt;td&gt;F&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;td&gt;&nbsp;&lt;/td&gt; &lt;/tr&gt; &lt;/tbody&gt; &lt;/table&gt;&lt;p&gt;&lt;strong&gt;ACKNOWLEDGEMENTS&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We thank Dr. Jake Jordan, Roland Ferger, Elizabeth Wood, Dr. Maria Gulinello, Kevin Fisher, Dr. Mimi Kim and Dr. Sacha Sokoloski for technical advice, assistance and discussions. M.A.F. was supported by a Fulbright Scholarship. M.A.F. and K.D.M. were funded by The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. J.T.G. was supported by the Whitehall Foundation (Research Grant 2019-05-71) and the National Institutes of Health (NINDS R01NS125252-01A1). R.C.C. was supported by the National Institutes of Health (NEI R01EY030578, NIDA RF1DA056400). Confocal microscopy experiments were supported by a&nbsp; shared instrumentation grant (1S10OD025295-01A1). This article is dedicated to the memory of Dr. Paul S. Frenette (1965-2021) who provided invaluable encouragement and support for this project.&lt;/p&gt

Adult neurogenesis improves spatial information encoding in the mouse hippocampus - RetroAAV-RC

&lt;p&gt;&lt;strong&gt;In vivo two-photon imaging dataset for Frechou et al. "Adult neurogenesis improves spatial information encoding in the mouse hippocampus"&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This dataset includes data from retro-AAV injected mice that were housed in a regular cage (RC).&nbsp;&lt;/p&gt; &lt;p&gt;For each recording we included raw imaging data consisting of:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Individual frames (.tif files) from 3 consecutive 3 min Ca2+ imaging movies (which were concatenated for analysis)&lt;/li&gt; &lt;li&gt;Microscope settings metadata (Experiment.xml)&lt;/li&gt; &lt;li&gt;Mouse location data (Episode001.h5 in SyncData folder) containing rotary encoder and RFID data&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Some analyzed data is also included:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Suite2p analysis data (&lt;strong&gt;Suite2p&lt;/strong&gt; folder)&lt;/li&gt; &lt;li&gt;&lt;strong&gt;fluorescence.npy&nbsp;&lt;/strong&gt;contains raw fluorescence data (the F output of Suite2p data extraction). Rows are individual cells and columns are frames (i.e. timepoints) acquired at 15.253 Hz.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;positions.npy&nbsp;&lt;/strong&gt;contains the position of the mouse on the treadmill belt indexed from 0 to 100.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Both NumPy(.npy) files are the output of the Preprocessing.py code, part of the analysis pipeline used for data analysis in the original publication, which can be found at &lt;a href="https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis"&gt;https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis&lt;/a&gt;&lt;/p&gt; &lt;p&gt;All imaged mice were male. Refer to the original publication for additional information.&nbsp;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;ACKNOWLEDGEMENTS&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We thank Dr. Jake Jordan, Roland Ferger, Elizabeth Wood, Dr. Maria Gulinello, Kevin Fisher, Dr. Mimi Kim and Dr. Sacha Sokoloski for technical advice, assistance and discussions. M.A.F. was supported by a Fulbright Scholarship. M.A.F. and K.D.M. were funded by The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. J.T.G. was supported by the Whitehall Foundation (Research Grant 2019-05-71) and the National Institutes of Health (NINDS R01NS125252-01A1). R.C.C. was supported by the National Institutes of Health (NEI R01EY030578, NIDA RF1DA056400). Confocal microscopy experiments were supported by a&nbsp; shared instrumentation grant (1S10OD025295-01A1). This article is dedicated to the memory of Dr. Paul S. Frenette (1965-2021) who provided invaluable encouragement and support for this project.&lt;/p&gt

Adult neurogenesis improves spatial information encoding in the mouse hippocampus - Irr+EE

&lt;p&gt;&lt;strong&gt;In vivo two-photon imaging dataset for Frechou et al. "Adult neurogenesis improves spatial information encoding in the mouse hippocampus"&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This dataset includes data from mice that were irradiated to ablate adult neurogenesis and housed in an enriched environment (Irr+EE).&nbsp;&lt;/p&gt; &lt;p&gt;For each recording we included raw imaging data consisting of:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Individual frames (.tif files) from 3 consecutive 3 min Ca2+ imaging movies (which were concatenated for analysis)&lt;/li&gt; &lt;li&gt;Microscope settings metadata (Experiment.xml)&lt;/li&gt; &lt;li&gt;Mouse location data (Episode001.h5 in SyncData folder) containing rotary encoder and RFID data&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Some analyzed data is also included:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Suite2p analysis data (&lt;strong&gt;Suite2p&lt;/strong&gt; folder)&lt;/li&gt; &lt;li&gt;&lt;strong&gt;fluorescence.npy&nbsp;&lt;/strong&gt;contains raw fluorescence data (the F output of Suite2p data extraction). Rows are individual cells and columns are frames (i.e. timepoints) acquired at 15.253 Hz.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;positions.npy&nbsp;&lt;/strong&gt;contains the position of the mouse on the treadmill belt indexed from 0 to 100.&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;Both NumPy(.npy) files are the output of the Preprocessing.py code, part of the analysis pipeline used for data analysis in the original publication, which can be found at &lt;a href="https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis"&gt;https://github.com/GoncalvesLab/Frechou-et-al-Neurogenesis&lt;/a&gt;&lt;/p&gt; &lt;p&gt;All imaged mice were female. Refer to the original publication for additional information.&nbsp;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;ACKNOWLEDGEMENTS&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We thank Dr. Jake Jordan, Roland Ferger, Elizabeth Wood, Dr. Maria Gulinello, Kevin Fisher, Dr. Mimi Kim and Dr. Sacha Sokoloski for technical advice, assistance and discussions. M.A.F. was supported by a Fulbright Scholarship. M.A.F. and K.D.M. were funded by The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. J.T.G. was supported by the Whitehall Foundation (Research Grant 2019-05-71) and the National Institutes of Health (NINDS R01NS125252-01A1). R.C.C. was supported by the National Institutes of Health (NEI R01EY030578, NIDA RF1DA056400). Confocal microscopy experiments were supported by a&nbsp; shared instrumentation grant (1S10OD025295-01A1). This article is dedicated to the memory of Dr. Paul S. Frenette (1965-2021) who provided invaluable encouragement and support for this project.&lt;/p&gt