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Updated: Jun 27, 2026
Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
Activation of epidermal growth factor receptor ErbB1 attenuates inhibitory synaptic development in mouse dentate
Yuichi Abe1, Hiroyuki Nawa, Hisaaki Namba
1Department of Mol Neurobiol, Brain Res Inst, Niigata Univ, Niigata, Japan.
Abstract:
Ligands for the epidermal growth factor receptor ErbB1, such as epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha), negatively regulate synaptic maturation of GABAergic neurons in the developing neocortex. Here, we evaluated the effects of these ligands in vivo on developing inhibitory neurons in the dentate gyrus. Hippocampal slices were prepared from postnatal mice repeatedly challenged with EGF or from transgenic mice overexpressing TGFalpha. We monitored paired pulse depression of field population spikes evoked by perforant path stimulation to estimate the strength of local inhibition. Administration of EGF increased the paired pulse ratio, suggesting a reduction of inhibitory strength. A similar reduction was observed in TGFalpha transgenic mice. Monitoring miniature and evoked synaptic currents, we estimated EGF effects on synaptic input and output of GABAergic neurons. EGF treatment diminished the amplitude of excitatory postsynaptic currents (EPSCs) in the GABAergic neurons without affecting their miniature EPSCs. EGF also affected output strength of the GABAergic neurons: The frequency of miniature inhibitory postsynaptic currents (IPSCs) and the evoked IPSC/evoked EPSC ratio were decreased in granule cells. In parallel, EGF down-regulated the protein level of vesicular GABA transporter. Thus, ErbB1 ligands influence GABAergic inhibitory synaptic transmission in the developing dentate gyrus.
Insights
Epidermal growth factor receptor (EGFR) ligands like EGF and TGFalpha impair synaptic development in the brain. These ligands reduce the strength of inhibitory GABAergic neuron signaling in the developing dentate gyrus.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Epidermal growth factor receptor (EGFR) ligands, including epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha), are known to negatively regulate synaptic maturation.
- GABAergic neurons are crucial for inhibitory neurotransmission in the central nervous system, particularly during development.
Purpose of the Study:
- To investigate the in vivo effects of EGFR ligands (EGF and TGFalpha) on the synaptic function of developing inhibitory neurons in the dentate gyrus.
- To elucidate the impact of these ligands on both the input and output strength of GABAergic neurons.
Main Methods:
- Preparation of hippocampal slices from postnatal mice treated with EGF or overexpressing TGFalpha.
- Assessment of inhibitory strength using paired pulse depression of field population spikes.
- Monitoring of miniature and evoked synaptic currents (EPSCs and IPSCs) to evaluate synaptic transmission.
- Quantification of vesicular GABA transporter protein levels.
Main Results:
- EGF administration and TGFalpha overexpression led to an increased paired pulse ratio, indicating reduced local inhibition.
- EGF diminished the amplitude of excitatory postsynaptic currents (EPSCs) in GABAergic neurons.
- EGF decreased the frequency of miniature inhibitory postsynaptic currents (IPSCs) and the evoked IPSC/evoked EPSC ratio in granule cells.
- EGF treatment resulted in down-regulation of the vesicular GABA transporter protein.
Conclusions:
- Ligands targeting the epidermal growth factor receptor (ErbB1) significantly influence GABAergic inhibitory synaptic transmission.
- These findings highlight a critical role for EGFR signaling in the developmental regulation of inhibitory circuits in the hippocampus.
