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The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition
Brenda L Bloodgood1, Nikhil Sharma, Heidi Adlman Browne
11] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA [3].
Nature
|November 9, 2013
Summary
Behaviorally driven NPAS4 expression in mice rearranges inhibitory synapses on CA1 pyramidal neurons. This regulation increases somatic inhibition while decreasing dendritic inhibition, impacting neuronal output and plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Computational Neuroscience
Background:
- Inhibitory neurons regulate neural circuit information flow via synapses on pyramidal neurons.
- Somatic and dendritic inhibition differentially control neuronal excitability and plasticity.
- NPAS4 (NPAS4) is an activity-dependent transcription factor regulating inhibitory synapse number and function.
Purpose of the Study:
- To investigate the in vivo role of NPAS4 in coordinating inhibitory synapse distribution on distinct neuronal domains.
- To elucidate how NPAS4 affects somatic versus dendritic inhibition in hippocampal CA1 pyramidal neurons.
Main Methods:
- Utilized mouse models to study NPAS4 function in the hippocampus.
- Analyzed behaviorally driven NPAS4 expression and its impact on inhibitory synapse distribution.
- Investigated the role of NPAS4 target genes, such as brain-derived neurotrophic factor (BDNF), in mediating these effects.
Main Results:
- Behaviorally driven NPAS4 expression induced a redistribution of inhibitory synapses on CA1 pyramidal neurons.
- NPAS4 increased inhibitory synapse number on the cell body (soma) while decreasing it on apical dendrites.
- The NPAS4 target gene BDNF was identified as a mediator, specifically regulating somatic inhibition.
Conclusions:
- Sensory stimuli, via NPAS4 induction, differentially control the spatial features of neuronal inhibition.
- This spatial rearrangement restricts neuronal output by enhancing somatic inhibition.
- The findings suggest NPAS4 creates a dendritic environment permissive for plasticity by modulating inhibition.
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