Cited by 310Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition

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Bloodgood, Brenda L., Sharma, Nikhil, Browne, Heidi Adlman, Trepman, Alissa Z., Greenberg, Michael E.·2013·Nature

Abstract

A heterogeneous population of inhibitory neurons controls the flow of information through a neural circuit. Inhibitory synapses that form on pyramidal neuron dendrites modulate the summation of excitatory synaptic potentials and prevent the generation of dendritic calcium spikes. Precisely timed somatic inhibition limits both the number of action potentials and the time window during which firing can occur. The activity-dependent transcription factor NPAS4 regulates inhibitory synapse number and function in cell culture, but how this transcription factor affects the inhibitory inputs that form on distinct domains of a neuron in vivo was unclear. Here we show that in the mouse hippocampus behaviourally driven expression of NPAS4 coordinates the redistribution of inhibitory synapses made onto a CA1 pyramidal neuron, simultaneously increasing inhibitory synapse number on the cell body while decreasing the number of inhibitory synapses on the apical dendrites. This rearrangement of inhibition is mediated in part by the NPAS4 target gene brain derived neurotrophic factor (Bdnf), which specifically regulates somatic, and not dendritic, inhibition. These findings indicate that sensory stimuli, by inducing NPAS4 and its target genes, differentially control spatial features of neuronal inhibition in a way that restricts the output of the neuron while creating a dendritic environment that is permissive for plasticity.

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Authors
Bloodgood, B. L., Sharma, N., Browne, H. A., Trepman, A. Z., & Greenberg, M. E.
Affiliations
Harvard University (US)
Corresponding author
Greenberg, Michael E.
Venue
Nature
Published
2013-11
Volume
503
Issue
7474
Pages
121-125
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2036442917
Cited by
310
References
30
Citations by year
2026: 17 · 2025: 25 · 2024: 27 · 2023: 17 · 2022: 29 · 2021: 31 · 2020: 19 · 2019: 22 · 2018: 25 · 2017: 26 · 2016: 30 · 2015: 20 · 2014: 20 · 2013: 2
FWCI
11.78
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (NS028829, P01NS047572, R01NS028829, P30NS047101, R37NS028829)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
Npas4, brain-derived neurotrophic factor, inhibitory synapses, dendritic inhibition, somatic inhibition, sensory enrichment, hippocampus, CA1 pyramidal neurons, activity-dependent transcription, dendritic plasticity
MeSH terms
Animals, Dendrites, Female, Hippocampus, Male, Neural Inhibition, Neuronal Plasticity, Neurons, Synapses, Pyramidal Cells, Mice, Knockout, Brain-Derived Neurotrophic Factor, Mice, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors

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