mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Area of Science:

• Neuroscience
• Molecular Biology

Background:

• Ketamine's antidepressant effects involve the mammalian target of rapamycin (mTOR) signaling pathway.
• mTOR signaling is a key target for preclinical depression research, but its causal role in depression remains unclear.

Purpose of the Study:

• To investigate the causal relationship between mTOR expression in specific medial prefrontal cortex (mPFC) regions and depressive-like behaviors.
• To determine if mTOR knockdown in the infralimbic (IL) or prelimbic (PrL) cortices affects depressive and anxious behaviors.

Main Methods:

• Utilized small interfering RNA (siRNA) to acutely knock down mTOR expression in the IL and PrL cortices of mice.
• Assessed depressive-like behaviors using the forced swimming test (FST) and tail suspension test (TST).
• Measured mTOR mRNA and protein levels, brain-derived neurotrophic factor (BDNF) expression, and neurotransmitter release (serotonin and glutamate).

Main Results:

• mTOR knockdown specifically in the IL cortex, but not the PrL cortex, induced significant depressive-like behaviors.
• This behavioral change correlated with reduced mTOR expression in the IL cortex.
• Decreased BDNF expression was observed in both IL and PrL cortices, alongside altered serotonin and glutamate release in the dorsal raphe nucleus (DRN).

Conclusions:

• Demonstrates a causal link between mTOR expression in the IL cortex and the manifestation of depressive-like behaviors.
• Suggests that mTOR signaling in the IL cortex plays a specific role in depression, independent of anxiety.
• Highlights the importance of IL cortex mTOR signaling in the neurobiology of depression.