Manipulation of a genetically and spatially defined sub-population of BDNF-expressing neurons potentiates learned fear and decreases hippocampal-prefrontal synchrony in mice

Henry L. Hallock, Henry M. Quillian, Yishan Mai, Kristen R. Maynard, Julia L. Hill, Keri Martinowich

Research output: Contribution to journalArticle

Abstract

Brain-derived neurotrophic factor (BDNF) signaling regulates synaptic plasticity in the hippocampus (HC) and prefrontal cortex (PFC), and has been extensively linked with fear memory expression in rodents. Notably, disrupting BDNF production from promoter IV-derived transcripts enhances fear expression in mice, and decreases fear-associated HC-PFC synchrony, suggesting that Bdnf transcription from promoter IV plays a key role in HC-PFC function during fear memory retrieval. To better understand how promoter IV-derived BDNF controls HC-PFC connectivity and fear expression, we generated a viral construct that selectively targets cells expressing promoter IV-derived Bdnf transcripts (“p4-cells”) for tamoxifen-inducible Cre-mediated recombination (AAV8-p4Bdnf-ERT2CreERT2-PEST). Using this construct, we found that ventral hippocampal (vHC) p4-cells are recruited during fear expression, and that activation of these cells causes exaggerated fear expression that co-occurs with disrupted vHC-PFC synchrony in mice. Our data highlight how this novel construct can be used to interrogate genetically defined cell types that selectively contribute to BDNF-dependent behaviors.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StatePublished - Jan 1 2019

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Brain-Derived Neurotrophic Factor
Fear
Prefrontal Cortex
Neurons
Hippocampus
Population
Neuronal Plasticity
Tamoxifen
Genetic Recombination
Rodentia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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Manipulation of a genetically and spatially defined sub-population of BDNF-expressing neurons potentiates learned fear and decreases hippocampal-prefrontal synchrony in mice. / Hallock, Henry L.; Quillian, Henry M.; Mai, Yishan; Maynard, Kristen R.; Hill, Julia L.; Martinowich, Keri.

In: Neuropsychopharmacology, 01.01.2019.

Research output: Contribution to journalArticle

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