About

Brenda Bloodgood is a researcher focused on understanding how neuronal computations change in response to an animal's interactions with the environment. Her lab investigates how experience, through activity-dependent gene expression, regulates the connectivity of inhibitory and excitatory neurons and how these processes relate to animal behavior and disease states. Her studies are performed in the mouse hippocampus to leverage its role in spatial learning and memory and its well-characterized circuit architecture. Her experimental approaches are multidisciplinary, involving manipulation of gene expression and molecular function in specific cell types, as well as probing synaptic connectivity with techniques such as optogenetics, viral circuit tracing, two-photon uncaging of neurotransmitters, and electrophysiology.

Research topics

• Biology
• Neuroscience
• Psychology
• Genetics
• Computer Science
• Biochemistry
• Cell biology
• Pathology

Selected publications

• NPAS4 refines spatial and temporal firing in CA1 pyramidal neurons

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-22

  articleOpen accessSenior author

  ABSTRACT NPAS4 is an activity-dependent transcription factor that, in CA1 of the hippocampus, regulates inhibitory synapses made onto the active pyramidal neuron. In principle, NPAS4 thereby allows the past activity of a neuron to influence how it encodes information, although this has not yet been demonstrated. Here, we generated a sparse, CA1-specific knockout (KO) of NPAS4 in the mouse hippocampus and used optogenetic tagging to identify KO neurons in vivo . Recordings from intermingled wild-type (WT) and KO neurons in awake behaving animals revealed that NPAS4 deletion degrades spatial representations and temporal precision of spiking: KO neurons exhibited larger place fields with reduced in-field firing and increased out-of-field firing, less stable place fields, reduced coupling to local field potential theta oscillations, and diminished phase precession. These findings demonstrate that NPAS4 plays a crucial role in refining the spatial and temporal properties of CA1 pyramidal neuron spikes, which themselves are thought to be fundamental building blocks of more complex processes such as learning and memory.

  PublisherDOI

• Intersection of transient cell states with stable cell types in hippocampus

  eLife · 2025-12-22

  articleOpen accessSenior author

  The transcriptome of a brain cell encodes both its stable identity and its dynamic responses to environmental stimuli. While significant progress has been made in categorizing cell types within the brain, deciphering to what extent transcriptional identity and transcriptional state are related remains a major technical and conceptual challenge. Here, we present a single-nucleus RNA-sequencing atlas of the mouse hippocampus spanning physiological and pathological stimuli and multiple circadian phases, enabling unified analysis of activity-, circadian-, and cell-type-dependent transcriptional programs. Taxonomically assigned cell types are largely stable despite the induction of different activity states, with a notable exception in the dentate gyrus. Activity and circadian rhythm each drive robust, largely nonoverlapping transcriptional responses, with convergent regulation on genes involved in specific pathways, including endocannabinoid signaling, excitability, and chromatin remodeling. These results underscore the necessity of integrating cell-type taxonomy with transcriptional state to capture how diverse cell types respond to experience.

  PublisherOA PDFDOI

• Reviewer #2 (Public review): Intersection of transient cell states with stable cell types in hippocampus

  2025-12-22

  peer-reviewOpen accessSenior author

  The transcriptome of a brain cell encodes both its stable identity and its dynamic responses to environmental stimuli. While significant progress has been made in categorizing cell types within the brain, deciphering to what extent transcriptional identity and transcriptional state are related remains a major technical and conceptual challenge. Here, we present a single-nucleus RNA-sequencing atlas of the mouse hippocampus spanning physiological and pathological stimuli and multiple circadian phases, enabling unified analysis of activity-, circadian-, and cell-type-dependent transcriptional programs. Taxonomically assigned cell types are largely stable despite the induction of different activity states, with a notable exception in the dentate gyrus. Activity and circadian rhythm each drive robust, largely nonoverlapping transcriptional responses, with convergent regulation on genes involved in specific pathways, including endocannabinoid signaling, excitability, and chromatin remodeling. These results underscore the necessity of integrating cell-type taxonomy with transcriptional state to capture how diverse cell types respond to experience.

  PublisherDOI

• Intersection of transient cell states with stable cell types in hippocampus

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-19 · 1 citations

  preprintSenior author

  The transcriptome of a brain cell encodes both its stable identity and its dynamic responses to environmental stimuli. While significant progress has been made in categorizing cell types within the brain, deciphering to what extent transcriptional identity and transcriptional state are related remains a major technical and conceptual challenge. Here, we present a single-nucleus RNA-sequencing atlas of the mouse hippocampus spanning physiological and pathological stimuli and multiple circadian phases, enabling unified analysis of activity-, circadian-, and cell-type-dependent transcriptional programs. Taxonomically assigned cell types are largely stable despite the induction of different activity states, with a notable exception in the dentate gyrus. Activity and circadian rhythm each drive robust, largely nonoverlapping transcriptional responses, with convergent regulation on genes involved in specific pathways, including endocannabinoid signaling, excitability, and chromatin remodeling. These results underscore the necessity of integrating cell-type taxonomy with transcriptional state to capture how diverse cell types respond to experience.

  PublisherDOI

• Intersection of transient cell states with stable cell types in hippocampus

  eLife · 2025-12-22

  articleOpen accessSenior author

  The transcriptome of a brain cell encodes both its stable identity and its dynamic responses to environmental stimuli. While significant progress has been made in categorizing cell types within the brain, deciphering to what extent transcriptional identity and transcriptional state are related remains a major technical and conceptual challenge. Here, we present a single-nucleus RNA-sequencing atlas of the mouse hippocampus spanning physiological and pathological stimuli and multiple circadian phases, enabling unified analysis of activity-, circadian-, and cell-type-dependent transcriptional programs. Taxonomically assigned cell types are largely stable despite the induction of different activity states, with a notable exception in the dentate gyrus. Activity and circadian rhythm each drive robust, largely nonoverlapping transcriptional responses, with convergent regulation on genes involved in specific pathways, including endocannabinoid signaling, excitability, and chromatin remodeling. These results underscore the necessity of integrating cell-type taxonomy with transcriptional state to capture how diverse cell types respond to experience.

  PublisherOA PDFDOI

• Experience-induced NPAS4 reduces dendritic inhibition from CCK+ inhibitory neurons and enhances plasticity

  Journal of Neurophysiology · 2025-06-30 · 1 citations

  articleOpen accessSenior authorCorresponding

  How does an inducible transcription factor affect neuronal and circuit function? Here we show that housing mice in an enriched environment induces NPAS4 expression in CA1 pyramidal neurons, leading to a reduction in dendritic inhibition specifically from cholecystokinin (CCK+) inhibitory neurons. This facilitates excitatory synaptic plasticity, indicating a potential mechanistic link between environmental enrichment and enhanced cognitive flexibility.

  PublisherDOI

• Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings

  Nature Communications · 2025-01-14 · 13 citations

  articleOpen access

  Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput. However, accessing intracellular potentials with NEAs remains challenging. This study presents an AI-supported technique that leverages thousands of synchronous eAP and iAP pairs from stem-cell-derived cardiomyocytes on NEAs. Our analysis revealed strong correlations between specific eAP and iAP features, such as amplitude and spiking velocity, indicating that extracellular signals could be reliable indicators of intracellular activity. We developed a physics-informed deep learning model to reconstruct iAP waveforms from extracellular recordings recorded from NEAs and Microelectrode arrays (MEAs), demonstrating its potential for non-invasive, long-term, high-throughput drug cardiotoxicity assessments. This AI-based model paves the way for future electrophysiology research across various cell types and drug interactions.

  PublisherOA PDFDOI

• Reviewer #1 (Public review): Intersection of transient cell states with stable cell types in hippocampus

  2025-12-22

  peer-reviewOpen accessSenior author

  The transcriptome of a brain cell encodes both its stable identity and its dynamic responses to environmental stimuli. While significant progress has been made in categorizing cell types within the brain, deciphering to what extent transcriptional identity and transcriptional state are related remains a major technical and conceptual challenge. Here, we present a single-nucleus RNA-sequencing atlas of the mouse hippocampus spanning physiological and pathological stimuli and multiple circadian phases, enabling unified analysis of activity-, circadian-, and cell-type-dependent transcriptional programs. Taxonomically assigned cell types are largely stable despite the induction of different activity states, with a notable exception in the dentate gyrus. Activity and circadian rhythm each drive robust, largely nonoverlapping transcriptional responses, with convergent regulation on genes involved in specific pathways, including endocannabinoid signaling, excitability, and chromatin remodeling. These results underscore the necessity of integrating cell-type taxonomy with transcriptional state to capture how diverse cell types respond to experience.

  PublisherDOI
• RETRACTED

  Retraction Notice to: Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers

  Cell · 2024-06-12

  retractionSenior author
  PublisherOA PDFDOI

• Electrical signals in the ER are cell type and stimulus specific with extreme spatial compartmentalization in neurons

  Cell Reports · 2023 · 20 citations

  Senior authorCorresponding
  • Neuroscience
  • Biology
  • Cell biology

  channels. Thus, segments of ER can generate large depolarizations that are actively restricted from impacting nearby, contiguous membrane.

  PublisherOA PDFDOI

Recent grants

• Neurosciences Graduate Training Program

  NIH · $7.2M · 2008–2026

Frequent coauthors

• Bernardo L. Sabatini

  Howard Hughes Medical Institute

  15 shared

• Anna Devor

  Boston University

  9 shared

• Michael E. Greenberg

  9 shared

• Nikhil Sharma

  5 shared

• Matthieu Vandenberghe

  Oslo University Hospital

  5 shared

• Joseph R. Ecker

  Salk Institute for Biological Studies

  5 shared

• Srdjan Djurovic

  University of Oslo

  5 shared

• Ole A. Andreassen

  Oslo University Hospital

  5 shared

Labs

• Bloodgood LabPI

Education

• PhD, Neurobiology

  Harvard Medical School

  2006

• BS, Division of Biological Sciences

  UC San Diego

  2001