Functional connectivity between brain stem midline neurons with respiratory-modulated firing rates

1. Recent evidence supports the idea that neurons distributed along the midline of the brain stem contribute to the regulation of breathing. This study sought evidence for functional connections between midline neurons with respiratory-modulated firing rates. 2. Experiments were conducted on 38 anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor spike trains of two or more midline neurons simultaneously in the regions of n. raphe obscurus, n. raphe pallidus, and n. raphe magnus. Efferent phrenic nerve activity was recorded. Data were analyzed with auto- and cross-correlograms and cycle-triggered histograms. Spike trains of neurons were also tested for respiratory modulation by an analysis of variance with the use of a subjects-by-treatments experimental design. 3. Of 584 neurons studied, 99.1% were tonic, i.e., they had firing probabilities greater than zero in all phases of the respiratory cycle. Fifty-three percent of the neurons had respiratory-modulated firing rates; 223 cells were more active during the expiratory (E) interval; 88 neurons were inspiratory (I)-related. The remaining cells were classified as having no respiratory-related modulation of firing rate (NRR). 4. The spike trains of 210 of 1,078 pairs (19.5%) of brain stem midline neurons exhibited short-time scale correlations indicative of paucisynaptic interactions. Primary cross-correlogram features included 129 central peaks, 45 offset peaks, two central troughs, and 57 offset troughs. Twenty-two of the neuronal pairs analyzed had both offset peaks and troughs. Correlograms from an additional 35 pairs of neurons had multiple peaks and troughs without a significant primary feature. 5. The frequency of correlations for neuron pairs composed of cells with respiratory-modulated firing rates was as follows: E-E, 40/185 (22%); E-I, 23/111 (21%); E-NRR, 45/297 (15%); I-I, 11/25 (44%); and I-NRR, 13/104 (13%). Twenty-two percent of the NRR pairs (79/357) exhibited short-time scale correlations. 6. Thirty pairs of neurons included a cell with an antidromically identified axonal projection extending to at least the third cervical segment. The mean estimated conduction velocity based on the single-site stimulation method was 26.5 +/- 9.9 (SD) m/s. 7. The results provide evidence for inhibitory and excitatory functional connections between midline brain stem neurons. Data support the hypothesis that the respiratory-modulated discharge patterns of midline neurons are, at least in part, a consequence of the synaptic actions of other midline cells.(ABSTRACT TRUNCATED AT 400 WORDS)