Excitatory and inhibitory synaptic inputs shape the discharge pattern of pump neurons of the nucleus tractus solitarii in the rat.
The second-order relay neurons of the slowly-adapting pulmonary stretch receptors (SARs) are called pump neurons (P cells) and are located in the nucleus tractus solitarii (NTS). We have shown recently that P cells do not act merely as simple relay neurons of SAR afferents but also receive rhythmic inputs from the central respiratory system. This study aimed to analyze two aspects of the respiratory inputs to P cells: (1) suppression of P cell firing at early inspiration (eI suppression) and (2) facilitation of P cell firing at around the period from late inspiration to early expiration (IE facilitation). This study employed extracellular recordings combined with iontophoretic applications of neuroactive drugs to single P cells, in Nembutal-anesthetized, paralyzed, and artificially ventilated rats. The results showed that several excitatory and inhibitory neurotransmitters were involved in these synaptic events. First, the glycine antagonist strychnine and the GABA(A) antagonist bicuculline were applied to identify the neurotransmitters acting in eI suppression. Strychnine greatly diminished eI suppression, but bicuculline had little effect. This suggested that eI suppression was elicited by inspiratory neurons that were glycinergic and had a decrementing firing pattern. Second, on the other hand bicuculline markedly enhanced IE facilitation as well as the baseline frequency of P cell firing. The enhancement of IE facilitation was distinctive even when the effects of increased baseline firing on this enhancement were taken into account. Third, IE facilitation was diminished by applications of the NMDA glutamate receptor antagonists D-2-amino-5-phosphonovaleric acid (APV) and dizocilpine (MK-801). These results suggested that glutamatergic synapses on P cells from some unidentified respiratory neurons form excitatory inputs for IE facilitation and GABA(A) receptor-mediated processes control the strength of IE facilitation, possibly at the presynaptic level. Finally, iontophoretic application of the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione disodium (CNQX), almost completely abolished P cell firing in response to both lung inflation and electrical stimulation of the vagus nerve. This confirmed the previous report that glutamate is the primary neurotransmitter at the synapses between SAR afferents and P cells. We concluded that complicated synaptic inputs involving glycinergic and GABAergic inhibitions, and non-NMDA and NMDA glutamate receptor-mediated excitations form the basic pattern of P cell firing.
Miyazaki
M
M
Department of Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan. ezurek@tmin.ac.jp
Tanaka
I
I
Ezure
K
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017552:Solitary Nucleus / Q000166:cytology* / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D013331:Strychnine; C080629:saclofen; D005998:Glycine; D001640:Bicuculline