Development of in vivo ventilatory and single chemosensitive neuron responses to hypercapnia in rats

We used pressure plethysmography to study breathing patterns of neonatal an d adult rats acutely exposed to elevated levels of CO2. Ventilation (V over dotE) increased progressively with increasing inspired CO2. The rise in V over dotE was associated with an increase in tidal volume, but not respirat ory rate. In all animals studied, the CO2 sensitivity (determined from the slope of the V over dotE vs. inspired % CO2 curve) was variable on a day to day basis. Chemosensitivity was high in neonates I day after birth (PI) an d fell throughout the first week to a minimum at about P8. Chemosensitivity rose again to somewhat higher values in P10 through adult rats. The develo pmental pattern of these in vivo ventilatory responses was different than i ndividual locus coeruleus (LQ neuron responses to increased CO2. The membra ne potential (V-m) of LC neurons was measured using perforated patch (ampho tericin B) techniques in brain slices. At all ages studied, LC neurons incr eased their firing rate by similar to 44% in response to hypercapnic acidos is (10% CO2, pH 7.0). Thus the in vivo ventilatory response to hypercapnia was not correlated with the V-m response of individual LC neurons to hyperc apnic acidosis in neonatal rats. These data suggest that CO2 sensitivity of ventilation in rats may exist in two forms, a high-sensitivity neonatal (o r fetal) form and a lower-sensitivity adult form, with a critical window of very low sensitivity during the period of transition between the two (simi lar to P8). (C) 2001 Elsevier Science B.V. All rights reserved.