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

We used pressure plethysmography to study breathing patterns of neonatal and adult rats acutely exposed to elevated levels of CO₂. Ventilation ($\text{V}\text{̇}$e) increased progressively with increasing inspired CO₂. The rise in $\text{V}\text{̇}$e was associated with an increase in tidal volume, but not respiratory rate. In all animals studied, the CO₂ sensitivity (determined from the slope of the $\text{V}\text{̇}$e vs. inspired % CO₂ curve) was variable on a day to day basis. Chemosensitivity was high in neonates 1 day after birth (P1) and fell throughout the first week to a minimum at about P8. Chemosensitivity rose again to somewhat higher values in P10 through adult rats. The developmental pattern of these in vivo ventilatory responses was different than individual locus coeruleus (LC) neuron responses to increased CO₂. The membrane potential (V_m) of LC neurons was measured using perforated patch (amphotericin B) techniques in brain slices. At all ages studied, LC neurons increased their firing rate by ∼44% in response to hypercapnic acidosis (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 hypercapnic acidosis in neonatal rats. These data suggest that CO₂ sensitivity of ventilation in rats may exist in two forms, a high-sensitivity neonatal (or fetal) form and a lower-sensitivity adult form, with a critical window of very low sensitivity during the period of transition between the two (∼P8).