Loss of FKBP5 Affects Neuron Synaptic Plasticity: An Electrophysiology Insight

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• FKBP5 (FKBP51) is a glucocorticoid receptor (GR) binding protein involved in GR regulation.
• FKBP5's role in disease development, particularly mental disorders, is not well understood.
• Long-term potentiation (LTP) is crucial for learning and memory but is impaired in many mental diseases.

Purpose of the Study:

• To investigate the function of FKBP5 in neuronal synaptic plasticity.
• To explore the impact of FKBP5 deficiency on LTP and associated signaling pathways.

Main Methods:

• Comparison of LTP in Fkbp5 knockout (KO) mice and wild-type (WT) mice.
• Analysis of glutamatergic and GABAergic signaling pathways in the hippocampus.
• Measurement of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs).
• Assessment of glutamate receptor and GABA expression levels.

Main Results:

• Fkbp5 KO mice exhibited reduced LTP compared to WT mice.
• Decreased excitatory synaptic activity (lower mEPSC frequency) and reduced expression of glutamate receptors (NMDAR1, NMDAR2B, AMPAR) were observed in KO mice.
• Enhanced inhibitory neurotransmission in KO mice, with increased GABA expression (driven by GAD65) and higher mIPSC frequency, indicating increased presynaptic GABA release.

Conclusions:

• FKBP5 plays a significant role in regulating neuronal synaptic plasticity.
• FKBP5 deficiency alters both excitatory and inhibitory neurotransmission.
• The Fkbp5 KO mouse model is valuable for studying FKBP5's role in neurological function and disease.