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Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice
Published on: March 1, 2014
Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia
Zhiqian Yu1, Mai Sakai2, Hotaka Fukushima3
1Department of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Abstract:
Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning.
Insights
Microglia gene expression changes during fear memory formation. Synapse-related genes increase, while immune genes decrease, suggesting a link between microglia, neurons, and immune responses in fear conditioning.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia, the brain's immune cells, are implicated in fear memory formation.
- The precise mechanisms linking microglia activity to neuronal function during fear conditioning are not fully understood.
Purpose of the Study:
- To investigate the transcriptional changes in microglia during contextual fear conditioning and extinction.
- To explore the role of microglia-neuron communication in fear memory.
Main Methods:
- Transcriptional profiling of microglia from a mouse model of contextual fear conditioning.
- Analysis of gene expression changes during fear memory consolidation and extinction.
- Comparison of microglial and monocyte transcription profiles.
Main Results:
- Fear memory consolidation significantly increased synapse-related genes and decreased immune-related genes in microglia.
- Synapse-related gene expression returned to baseline after fear memory extinction, but immune gene expression did not.
- Hippocampal microglia showed increased expression of neurotransmitter regulators (GABRB3, synapsin 1/2) during fear consolidation, which decreased after extinction.
Conclusions:
- Microglia-neuron communication is a key mediator of contextual fear conditioning.
- Fear conditioning induces distinct microglial transcriptional changes, including alterations in synaptic and immune gene expression.
- The observed changes suggest a dysregulated immune response following contextual fear conditioning.
