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Role of GlyT 2 expressing neurons in the Bötzinger Complex for respiratory rhythm and pattern generation
Author(s) -
Abdala Ana Paula Lima,
Liu Beihui H.,
Rybak Ilya A.,
Smith Jeffrey C.,
Paton Julian F. R.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.614.3
Subject(s) - glycine receptor , neuroscience , respiratory system , receptor , glycine , inhibitory postsynaptic potential , respiratory center , strychnine , biology , chemistry , anatomy , biochemistry , amino acid
Computational modeling of the respiratory network and experimental data both suggest that reciprocal inhibition between post‐inspiatory (post‐I) and augmenting expiratory neurons is essential for normal breathing: e.g. global blockade of glycinergic receptors abolishes post‐I activity in motor outflow. Here, we found a way to selectively inactivate glycinergic neurons in the Bötzinger Complex (BötC). For that, we generated a novel lentiviral vector to specifically express allatostatin receptors (AstR) under the control of the glycine transporter‐2 (GlyT 2 ) gene promoter , which is a reliable marker for glycinergic neurons. Binding of exogenously applied allatostatin (AL) to the AlstR inhibits the target neurons. The lentivirus was injected bilaterally (109 pfu) into the BötC of Wistar rats. After 10 days, we simultaneously recorded phrenic (PN), hypoglossal (HN) and central vagal (cVN) nerves in these rats in situ . We applied AL (1 μM) systemically to selectively inhibit glycinergic neurons in the BötC, which markedly reduced PN amplitude changing its pattern from a ramp to a ‘square‐wave’ or ‘bell’ shape. AL also reduced the post‐I component in the cVN and increased respiratory rate. These effects were reversed by washing out AL. We conclude that GlyT 2 expressing neurons in the BötC are critical for generation of an eupneic‐like respiratory pattern with the normally expressed post‐I activity. Support NIH R01 NS057815.