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Updated: Jul 19, 2026

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Trace Fear Conditioning in Mice
Published on: March 20, 2014
Synaptically released zinc gates long-term potentiation in fear conditioning pathways
Sodikdjon A Kodirov1, Shuichi Takizawa, Jamie Joseph
1*Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
Summary
Synaptically released zinc (Zn2+) enables fear learning by enhancing synaptic plasticity in the amygdala. Zinc transporter 3 (ZnT-3) is crucial for this process, regulating synaptic modifications in neural circuits.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Neurochemistry
Background:
- The role of releasable Zn2+ in the central nervous system is not well understood.
- Zinc transporter 3 (ZnT-3) concentrates Zn2+ in synaptic vesicles and marks zinc-containing neurons.
- ZnT-3 is found in the amygdala and auditory cortex, key areas for auditory fear learning.
Purpose of the Study:
- To investigate the functional role of Zn2+ release in synaptic plasticity within the auditory cortex and amygdala.
- To determine if ZnT-3 enrichment in specific brain regions is linked to auditory fear learning pathways.
- To elucidate the mechanism by which Zn2+ influences synaptic modifications in the cortico-amygdala pathway.
Main Methods:
- Utilized whole-cell recordings in amygdala slices.
- Investigated the role of activity-dependent Zn2+ release in spike timing-dependent long-term potentiation (STDP).
- Examined the distribution of ZnT-3 in auditory cortex and amygdala regions relevant to conditioned stimulus processing.
Main Results:
- Activity-dependent release of chelatable Zn2+ is essential for inducing STDP in the amygdala's cortical input.
- Synaptically released Zn2+ facilitates long-term potentiation at cortico-amygdala synapses.
- Zn2+ depresses feed-forward GABAergic inhibition, enhancing plasticity in principal neurons.
Conclusions:
- Synaptically released Zn2+ plays a critical role in fear learning by modulating synaptic plasticity in the cortico-amygdala pathway.
- The pathway-dependent release of Zn2+ ensures spatial specificity of synaptic modifications in learned behaviors.
- ZnT-3's enrichment in specific pathways highlights its importance in regulating neural circuits for learned behaviors.
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