Tumor necrosis factor-alpha mediates one component of competitive, experience-dependent plasticity in developing...

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Experience-dependent plasticity in the developing visual cortex is traditionally viewed as competitive.
• Monocular deprivation leads to decreased responses to the deprived eye and increased responses to the open eye.

Purpose of the Study:

• To investigate the role of Tumor Necrosis Factor-alpha (TNFα) in visual cortex plasticity.
• To elucidate the mechanisms underlying experience-dependent synaptic scaling and neuronal response changes.

Main Methods:

• Chronic optical imaging in mice genetically deficient in TNFα.
• In vitro electrophysiology to assess miniature excitatory postsynaptic currents (mEPSCs) and long-term potentiation (LTP).
• Pharmacological inhibition of endogenous TNFα in wild-type mice.

Main Results:

• TNFα-deficient mice showed normal initial loss of deprived-eye responses but lacked the subsequent increase in open-eye responses.
• Homeostatic synaptic scaling of mEPSCs in the visual cortex was abolished in TNFα mutants.
• Reduced responses were observed in the monocular zone of TNFα mutants, similar to the binocular zone.
• Pharmacological TNFα inhibition mimicked the knockout phenotype.

Conclusions:

• Experience-dependent competition in the visual cortex involves two distinct processes: deprived-eye response loss and TNFα-dependent homeostatic response increase.
• TNFα signaling is essential for the homeostatic component of visual cortex plasticity.
• These findings challenge the purely competitive model of visual cortex development.