Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the...

Area of Science:

• Neuroscience
• Neuroimmunology
• Psychiatry

Background:

• Stress can trigger neuropsychiatric conditions like anxiety and schizophrenia.
• The temporal neocortex is a stress-sensitive brain region implicated in these disorders.
• Aseptic inflammation and stress can shift synaptic balance towards excitation in the temporal cortex.

Purpose of the Study:

• To investigate if the anti-inflammatory reflex can mitigate central nervous system responses to aseptic inflammation.
• To explore the role of the anti-inflammatory reflex in modulating synaptic function in the temporal cortex.

Main Methods:

• Aseptic inflammation was induced using lipopolysaccharide (LPS) injections in rats.
• The anti-inflammatory reflex was activated pharmacologically (nicotinic α7 receptor agonist PHA543613) or physiologically (vagal nerve stimulation, VNS).
• Patch-clamp recordings were used to assess synaptic function, specifically the inhibitory-to-excitatory ratio.

Main Results:

• Activation of the anti-inflammatory reflex blocked or reduced LPS-induced decreases in the inhibitory-to-excitatory synaptic ratio.
• Both pharmacological and physiological activation of the reflex normalized inhibitory current input-output curves.
• These findings demonstrate the reflex's ability to counteract inflammation-induced synaptic hyperexcitability.

Conclusions:

• The anti-inflammatory reflex effectively counteracts the effects of aseptic inflammation on synaptic inhibition in the temporal cortex.
• Available α7 nicotinic receptor agonists and clinical VNS present a promising therapeutic strategy for stress-induced hyperexcitable neuropsychiatric conditions.
• This research suggests a novel therapeutic avenue for conditions involving decreased synaptic inhibition in the temporal cortex.