Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

Abstract Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

• Publication year

  2017

• Venue

  eNeuro

• Publication date

  2017-05-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/ENEURO.0207-17.2017PMID 28932809PMCID 5604087
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genetic evidence that Nkx2.2 acts primarily downstream of Neurog3 in pancreatic endocrine lineage development

  2017cited by this paper
• An extended retinotopic map of mouse cortex

  2017cited by this paper
• A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging

  2016cited by this paper
• A mathematical model explains saturating axon guidance responses to molecular gradients

  2016cited by this paper
• Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice

  2016cited by this paper
• Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol

  2016cited by this paper
• Making Decisions under Ambiguity: Judgment Bias Tasks for Assessing Emotional State in Animals

  2016cited by this paper
• Wide field-of-view, multi-region two-photon imaging of neuronal activity in the mammalian brain

  2016cited by this paper
• The Neurobiology of Cannabis Use Disorders: A Call for Evidence

  2016cited by this paper
• Large-scale imaging of cortical dynamics during sensory perception and behavior.

  2016influential reference
• Intact skull chronic windows for mesoscopic wide-field imaging in awake mice.

  2016cited by this paper
• Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.

  2015cited by this paper
• GABAergic inhibition shapes interictal dynamics in awake epileptic mice.

  2015cited by this paper
• Wide field-of-view, multi-region two-photon imaging of neuronal activity in vivo

  2015cited by this paper
• Thy1-GCaMP6 Transgenic Mice for Neuronal Population Imaging In Vivo

  2014cited by this paper
• Flow of cortical activity underlying a tactile decision in mice.

  2014cited by this paper
• How might novel technologies such as optogenetics lead to better treatments in epilepsy?

  2014cited by this paper
• How can we identify ictal and interictal abnormal activity?

  2014cited by this paper
• Issues in clinical epileptology : a view from the bench

  2014cited by this paper
• Ultra-sensitive fluorescent proteins for imaging neuronal activity

  2013cited by this paper
• Two lines of transgenic mice expressing cre-recombinase exhibit increased seizure susceptibility.

  2013influential reference
• Strain Background Influences Neurotoxicity and Behavioral Abnormalities in Mice Expressing the Tetracycline Transactivator

  2012cited by this paper
• Interictal spikes: harbingers or causes of epilepsy?

  2011cited by this paper
• Spikes and Epilepsy

  2009cited by this paper
• The Natural History and Treatment of Epilepsy in a Murine Model of Tuberous Sclerosis

  2007cited by this paper
• Vagaries of conditional gene targeting

  2007influential reference
• Behavioral detection of tactile stimuli during 7–12 Hz cortical oscillations in awake rats

  2003cited by this paper
• Electroconvulsive thresholds of inbred mouse strains.

  2001influential reference
• The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit

  1998cited by this paper
• The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.

  1998cited by this paper
• Frontiers in Cellular Neuroscience Cellular Neuroscience Methods Article

  year unknowncited by this paper

• icBTnC2, a new green calcium indicator based on troponin C and mBaoJin, with enhanced photostability

  2026cites this paper
• In Vivo Analysis of Medial Perforant Path-Evoked Excitation and Inhibition in Dentate Granule Cells

  2025cites this paper
• Keratinocyte–TRPV1 sensory neuron interactions in a genetically controllable mouse model of chronic neuropathic itch

  2025cites this paper
• Quantitative dynamics of neural uncertainty in sensory processing and decision-making during discriminative learning

  2025cites this paper
• Enhanced proconvulsant sensitivity, not spontaneous rapid swimming activity, is a robust correlate of scn1lab loss-of-function in stable mutant and F0 crispant hypopigmented zebrafish expressing GCaMP6s

  2025cites this paper
• Suppressing cortical glutamatergic neurons produces paradoxical interictal discharges and seizures

  2025cites this paper
• Multimodal dataset linking wide‐field calcium imaging to behavior changes in operant lever‐pull task in mice

  2025cites this paper
• Local inhibitory circuits mediate cortical reactivations and memory consolidation

  2025cites this paper
• Brain-wide topographic coordination of traveling spiral waves

  2025cites this paper
• Spontaneous mesoscale calcium dynamics reflect the development of the modular functional architecture of the mouse cerebral cortex

  2025cites this paper
• Multiplexed subspaces route neural activity across brain-wide networks

  2025cites this paper
• Zebrafish models of developmental epileptic encephalopathy accurately reflect clinical electrographic biomarkers

  2025cites this paper
• Deep-tissue two-photon brain imaging enabled by a tunable fiber-optic dispersive wave generator

  2025cites this paper
• A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.

  2025cites this paper
• A standardized and reproducible behavioral protocol to elicit visual spatial attention in mice

  2025cites this paper
• A multimodal dataset linking wide-field calcium imaging to behavior changes in mice during an operant lever-pull task

  2025cites this paper
• Mapping uterine calcium dynamics during the ovulatory cycle in live mice

  2024cites this paper
• Wide-field imaging in behaving mice as a tool to study cognitive function

  2024cites this paper
• Development of a piggyBac transgenic system in Bactrocera dorsalis and its potential for research on olfactory molecular targets

  2024cites this paper
• Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses

  2024influential citation
• A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types

  2024cites this paper
• Epilepsy insights revealed by intravital functional optical imaging

  2024cites this paper
• Psilocybin decreases neural responsiveness and increases functional connectivity while preserving pure-tone frequency selectivity in mouse auditory cortex

  2024cites this paper
• Spatiotemporal relationships between neuronal, metabolic, and hemodynamic signals in the awake and anesthetized mouse brain

  2024cites this paper
• Imaging the large‐scale and cellular response to focal traumatic brain injury in mouse neocortex

  2024cites this paper
• The influence of cortical activity on perception depends on behavioral state and sensory context

  2024cites this paper
• Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex

  2024cites this paper
• Transient enhancement of stimulus-evoked activity in neocortex during sensory learning

  2024cites this paper
• Effects of unilateral hippocampal surgical procedures needed for calcium imaging on mouse behavior and adult hippocampal neurogenesis.

  2024cites this paper
• Window into the Brain: In Vivo Multiphoton Imaging

  2024cites this paper
• Cortical Reactivations Modulated by Local Inhibitory Circuits Mediate Memory Consolidation

  2024influential citation
• Aberrant hippocampal Ca2+ microwaves following synapsin-dependent adeno-associated viral expression of Ca2+ indicators

  2024cites this paper
• Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals

  2024cites this paper
• Differences in the expression of cortex-wide neural dynamics are related to behavioral phenotype.

  2024cites this paper
• Expression of GCaMP6s in the dentate gyrus induces tonic–clonic seizures

  2024influential citation
• Prominent in vivo influence of single interneurons in the developing barrel cortex

  2023cites this paper
• Deep-brain optical recording of neural dynamics during behavior.

  2023cites this paper
• A stable, distributed code for cue value in mouse cortex during reward learning

  2023cites this paper
• Multiplexed Subspaces Route Neural Activity Across Brain-wide Networks

  2023cites this paper
• Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease

  2023cites this paper
• Emergence of cortical network motifs for short-term memory during learning

  2023cites this paper
• Aberrant hippocampal Ca2+ micro-waves following synapsin-dependent adeno-associated viral expression of Ca2+ indicators

  2023cites this paper
• Development and characterization of novel jGCaMP8f calcium sensor variants with improved kinetics and fluorescence response range

  2023cites this paper
• Prelimbic neuron calcium activity predicts perceived hedonic value across drinking solutions and ethanol dependent states in mice

  2023cites this paper
• Distinct Features of Interictal Activity Predict Seizure Localization and Burden in a Mouse Model of Childhood Epilepsy

  2023cites this paper
• Stimulus novelty uncovers coding diversity in visual cortical circuits

  2023cites this paper
• Tetracycline transactivator overexpression in keratinocytes triggers a TRPV1 primary sensory neuron-dependent neuropathic itch

  2023cites this paper
• High fidelity sensory-evoked responses in neocortex after intravenous injection of genetically encoded calcium sensors

  2023cites this paper
• An updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice

  2023cites this paper
• Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex

  2023cites this paper
• Mesoscale calcium imaging in vivo: evolution and contribution to developmental neuroscience

  2023cites this paper
• Virtual reality-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism.

  2023cites this paper
• Tuning instability of non-columnar neurons in the salt-and-pepper whisker map in somatosensory cortex

  2022cites this paper
• Identifying mild traumatic brain injury using measures of frequency-specified networks

  2022cites this paper
• VR-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism

  2022cites this paper
• Embryonic cortical layer 5 pyramidal neurons form an active, transient circuit motif perturbed by autism-associated mutations

  2022cites this paper
• Repetitive nociceptive stimulation increases spontaneous neural activation similar to nociception-induced activity in mouse insular cortex

  2022cites this paper
• Neuronal Activity Reporters as Drug Screening Platforms

  2022cites this paper
• Two-photon calcium imaging of neuronal activity

  2022cites this paper
• Neural circuit dynamics of drug-context associative learning in the mouse hippocampus

  2022cites this paper
• Functional states shape the spatiotemporal representation of local and cortex-wide neural activity in mouse sensory cortex

  2022cites this paper
• Multiregion neuronal activity: the forest and the trees

  2022cites this paper
• In utero electroporation and cranial window implantation for in vivo wide-field two-photon calcium imaging using G-CaMP9a transgenic mice

  2022cites this paper
• Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo

  2022cites this paper
• Visual experience has opposing influences on the quality of stimulus representation in adult primary visual cortex

  2022cites this paper
• cNTnC and fYTnC2, Genetically Encoded Green Calcium Indicators Based on Troponin C from Fast Animals

  2022cites this paper
• Optogenetic Methods to Investigate Brain Alterations in Preclinical Models

  2022cites this paper
• Behaviorally relevant decision coding in primary somatosensory cortex neurons

  2022cites this paper
• A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in vivo

  2022cites this paper
• Genetically encoded fluorescent sensors for imaging neuronal dynamics in vivo

  2022cites this paper
• Longitudinal two-photon calcium imaging with ultra-large cranial window for head-fixed mice

  2022cites this paper
• Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X

  2022cites this paper
• Calcium imaging for analgesic drug discovery

  2022cites this paper
• Designing AAV Vectors for Monitoring the Subtle Calcium Fluctuations of Inferior Olive Network in vivo

  2022cites this paper
• Seeing beyond the spikes: reconstructing the complete spatiotemporal membrane potential distribution from paired intra‐ and extracellular recordings

  2022cites this paper
• Existing function in primary visual cortex is not perturbed by new skill acquisition of a non-matched sensory task

  2022cites this paper
• Use of Optical Probes for Visualizing Intracellular Calcium and Recording Action Potentials in Neurons

  2022cites this paper
• Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex.

  2022cites this paper
• Mouse frontal cortex mediates additive multisensory decisions

  2021cites this paper
• An Adversarial Variational Autoencoder Approach Toward Transfer Learning for mTBI Identification

  2021cites this paper
• Two-Photon Imaging to Unravel the Pathomechanisms Associated with Epileptic Seizures: A Review

  2021cites this paper
• A Convolutional Autoencoder for Identification of mild Traumatic Brain Injury

  2021cites this paper
• An updated suite of viral vectors for in vivo calcium imaging using local and retro-orbital injections

  2021cites this paper
• Methods of measuring presynaptic function with fluorescence probes

  2021cites this paper
• The role of frontal cortex in multisensory decisions

  2021cites this paper
• All-optical interrogation of neural circuits in behaving mice

  2021cites this paper
• Synchronous activity patterns in the dentate gyrus during immobility

  2021cites this paper
• A New Transgenic Mouse Line for Imaging Mitochondrial Calcium Signals

  2021cites this paper
• Neuronal representations of reward-predicting cues and outcome history with movement in the frontal cortex.

  2021cites this paper
• New skill acquisition does not perturb existing function in sensory cortex

  2021cites this paper
• Spatial modulation of visual responses arises in cortex with active navigation

  2021cites this paper
• Developmental impact of glutamate transporter overexpression on dopaminergic neuron activity and stereotypic behavior

  2021cites this paper
• Optogenetic Interrogation of Circuits Following Neurotrauma

  2021cites this paper
• Excess interictal activity marks seizure prone cortical areas and mice in a genetic epilepsy model

  2021cites this paper
• Striatal activity topographically reflects cortical activity

  2021cites this paper
• Imaging of Endoplasmic Reticulum Ca2+ in the Intact Pituitary Gland of Transgenic Mice Expressing a Low Affinity Ca2+ Indicator

  2021influential citation
• Fast and sensitive GCaMP calcium indicators for imaging neural populations

  2021cites this paper
• Letting the little light of mind shine: Advances and future directions in neurochemical detection.

  2021cites this paper
• Emerging strategies for the genetic dissection of gene functions, cell types, and neural circuits in the mammalian brain

  2021cites this paper
• An in vivo Calcium Imaging Approach for the Identification of Cell-Type Specific Patterns in the Developing Cortex

  2021cites this paper