DISTRIBUTED ACTIONS AND DYNAMIC ASSOCIATIONS IN RESPIRATORY-RELATED NEURONAL ASSEMBLIES OF THE VENTROLATERAL MEDULLA AND BRAIN-STEM MIDLINE- EVIDENCE FROM SPIKE TRAIN ANALYSIS

1. Considerable evidence indicates that neurons in the brain stem midl ine and ventrolateral medulla participate in the control of breathing. This work was undertaken to detect and evaluate evidence for function al links that coordinate the parallel operations of neurons distribute d in these two domains. 2. Data were from 51 Dial-urethan-anesthetized , bilaterally vagotomized, paralyzed, artificially ventilated cats. Pl anar arrays of tungsten microeiectrodes were used to monitor simultane ously spike trains in two or three of the following regions: n. raphe obscurus-n. raphe pallidus, n. raphe magnus, rostral ventrolateral med ulla, and caudal ventrolateral medulla. Efferent phrenic nerve activit y was recorded to indicate the phases of the respiratory cycle. Electr odes in the ventral spinal cord (C3) were used in antidromic stimulati on tests for spinal projections of neurons. 3. Spike trains of 1,243 n eurons were tested for respiratory modulated firing rates with cycle-t riggered histograms and an analysis of variance with the use of a subj ects-by-treatments experimental design. Functional associations were d etected and evaluated with cross-correlograms, snowflakes, and the gra vity method. 4. Each of 2,310 pairs of neurons studied included one ne uron monitored within 0.6 mm of the brain stem midline and a second ce ll recorded in the ventrolateral medulla; 117 of these pairs (5%) incl uded a neuron with a spinal projection, identified with antidromic sti mulation methods, that extended to at least the third cervical segment . Short-time scale correlations were detected in 110 (4.7%) pairs of n eurons. Primary cross-correlogram features included 40 central peaks, 47 offset peaks, 4 central troughs, and 19 offset troughs. 5. In 14 da ta sets, multiple short-time scale correlations were found among three or more simultaneously recorded neurons distributed between both midl ine and ventrolateral domains. The results suggested that elements of up to three layers of interneurons were monitored simultaneously. Evid ence for concurrent serial and parallel regulation of impulse synchron y was detected. Gravitational representations demonstrated respiratory -phase dependent synchrony among neurons distributed in both brain ste m regions. 6. The results support a model of the brain stem respirator y network composed of coordinated distributed subassemblies and provid e evidence for several hypotheses. 1) Copies of respiratory drive info rmation from rostral ventrolateral medullary (RVLM) respiratory neuron s are transmitted to midline neurons. 2) Midline neurons act on respir atory-related neurons in the RVLM to modulate phase timing. 3) Impulse synchrony of midline neurons is influenced by concurrent divergent ac tions of both midline and ventrolateral neurons. 4) Such putative dist ributed ''synchrony-promoting'' neurons are also functionally linked; changes in their effective connectivity may contribute to temporal var iations in the synchrony of midline assemblies.