1. There is increasing evidence that the kernel of the rhythm-generating circuitry for breathing is located within a discrete subregion of a column of respiratory neurons within the ventrolateral medulla referred to as the ventral respiratory group (VRG). It is less clear how this rhythm is transformed into the precise patterns appearing on the varied motor outflows.
2. Two different approaches were used to test whether subregions of the VRG have distinct roles in rhythm or pattern generation. In one, clusters of VRG neurons were activated or inactivated by pressure injection of small volumes of neuroactive agents to activate or inactivate groups of respiratory neurons and the resulting effects on respiratory rhythm and pattern were determined. The underlying assumption was that if rhythm and pattern are generated by neurons in different VRG subregions, then we should be able to identify regions where activation of neurons predominantly alters rhythm with little effect on pattern and other regions where pattern is altered with little effect on rhythm.
3. Based on the pattern of phrenic nerve responses to injection of an excitatory amino acid (DL-homocysteate), the VRG was divided into four subdivisions arranged along the rostrocaudal axis. Injections into the three rostral regions elicited changes in both respiratory rhythm and pattern. From rostral to caudal the regions included: (i) a rostral bradypnoea region, roughly associated with the Bötzinger complex; (ii) a dysrhythmia/tachypnoea area, roughly associated with the pre-Bötzinger complex (PBC); (iii) a second caudal bradypnoea area; and, most caudally, (iv) a region from which no detectable change in respiratory motor output was elicited.
4. In a second approach, the effect of unilateral lesions of one subregion, the PBC, on the Breuer–Hering reflex changes in rhythm were determined. Activation of this reflex by lung inflation shortens inspiration and lengthens expiration (TE).
5. Unilateral lesions in the PBC attenuated the reflex lengthening of TE, but did not change baseline respiratory rhythm.
6. These findings are consistent with the concept that the VRG is not functionally homogeneous, but consists of rostrocaudally arranged subregions. Neurons within the so-called PBC appear to have a dominant role in rhythm generation. Nevertheless, neurons within other subregions contribute to both rhythm and pattern generation. Thus, at least at an anatomical level resolvable by pressure injection, there appears to be a significant overlap in the circuitry generating respiratory rhythm and pattern.