Anisomycin activates p38 MAP kinase to induce LTD in mouse primary visual cortex.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Biology

Background:

• Anisomycin is a known protein synthesis inhibitor and activator of p38/JNK MAPK pathways.
• It has been utilized to inhibit long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus.

Purpose of the Study:

• To investigate the effects of anisomycin on synaptic transmission in the mouse primary visual cortex.
• To determine the specific molecular pathways involved in anisomycin-induced synaptic depression.
• To explore the relationship between anisomycin-induced LTD and electrically induced LTD.

Main Methods:

• Acute brain slices from mouse primary visual cortex were used.
• Field excitatory postsynaptic potentials (fEPSPs) were recorded to measure synaptic transmission.
• Anisomycin, emetine, and cycloheximide were applied to assess their effects.
• Specific inhibitors (SB203580 for p38, SP600125 for JNK) were used.
• A peptide blocking AMPA receptor endocytosis was applied.

Main Results:

• Anisomycin caused a time-dependent decrease in fEPSP magnitude in the visual cortex.
• This anisomycin-induced depression occluded NMDA receptor-dependent LTD induced by low-frequency stimulation (LFS).
• p38 MAPK inhibition (SB203580) rescued the anisomycin effect, while JNK inhibition (SP600125) did not.
• Blocking AMPA receptor endocytosis reduced the anisomycin-induced fEPSP decline.

Conclusions:

• Anisomycin induces long-term depression (LTD) in the mouse visual cortex via p38 MAPK activation.
• This p38 MAPK pathway activation leads to AMPA receptor endocytosis, causing synaptic depression.
• The findings suggest shared molecular mechanisms between anisomycin-induced LTD and electrically induced LTD.