Pattern-specific synaptic mechanisms in a multifunctional network. I. Effects of alterations in synapse strength

Area of Science:

• Neuroscience
• Respiratory Physiology
• Computational Neuroscience

Background:

• Mammalian neuronal networks often exhibit multifunctional activity, generating diverse patterns under varying conditions.
• The mechanisms underlying neural network reconfiguration remain largely unresolved.
• The mammalian respiratory network generates both normal breathing (eupnea) and distinct sigh patterns from a single network.

Purpose of the Study:

• To investigate the specific synaptic mechanisms differentiating the generation of eupnea and sighs in the mammalian respiratory network.
• To identify the role of different glutamatergic synapses and calcium channels in respiratory pattern generation.

Main Methods:

• Utilized in vitro transverse medullary slices of mice to preserve both eupneic and sigh rhythms.
• Administered specific antagonists: omega-agatoxin TK (P/Q-type calcium channel), 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, non-N-methyl-D-aspartate glutamate receptor), MK-801 (NMDA receptor), and omega-conotoxin GVIA (N-type calcium channel).
• Analyzed the effects of these antagonists on fictive eupnea and sigh generation.

Main Results:

• Fictive sighs were more sensitive than eupnea to reductions in excitatory synapse strength induced by omega-agatoxin TK and CNQX.
• MK-801 increased sigh occurrence while inhibiting eupnea, suggesting a subset of glutamatergic synapses crucial for sighs.
• Blockade of N-type calcium channels (omega-conotoxin GVIA) increased sigh frequency and decreased post-sigh apnea, without affecting eupnea.

Conclusions:

• A specific subset of glutamatergic synapses, sensitive to agatoxin and insensitive to NMDA receptor blockade, is essential for generating sighs.
• N-type calcium channels, potentially coupled to calcium-activated potassium channels, may play a selective role in generating post-sigh apnea.