Pattern-specific synaptic mechanisms in a multifunctional network. I. Effects of alterations in synapse strength.
Many neuronal networks are multifunctional, producing different patterns of activity in different circumstances, but the mechanisms responsible for this reconfiguration are in many cases unresolved. The mammalian respiratory network is an example of such a system. Normal respiratory activity (eupnea) is periodically interrupted by distinct large-amplitude inspirations known as sighs. Both rhythms originate from a single multifunctional neural network, and both are preserved in the in vitro transverse medullary slice of mice. Here we show that the generation of fictive sighs were more sensitive than eupnea to reductions of excitatory synapse strength caused by either the P/Q-type (alpha1A-containing) calcium channel antagonist omega-agatoxin TK or the non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX). In contrast, the NMDA receptor antagonist MK-801, while also inhibiting eupnea, increased the occurrence of sighs. This suggests that among the glutamatergic synapses subserving eupneic rhythmogenesis, there is a specific subset-highly sensitive to agatoxin and insensitive to NMDA receptor blockade-that is essential for sighs. Blockade of N-type calcium channels with omega-conotoxin GVIA also had pattern-specific effects: eupneic activity was not affected, but sigh frequency was increased and postsigh apnea decreased. We hypothesize that N-type (alpha1B) calcium channels selectively coupled to calcium-activated potassium channels contribute to the generation of the postsigh apnea.
Committee on Neurobiology, The University of Chicago, 1027 E. 57th S., Chicago, IL 60637-1508, USA.
Steven P
SP
Lieske
Jan-Marino
JM
Ramirez
D000200:Action Potentials / Q000502:physiology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D008526:Medulla Oblongata / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D015656:Respiratory Mechanics / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels