Functional Connectivity in the Pontomedullary Respiratory Network

Abstract

Current models propose that a neuronal network in the ventrolateral medulla generates the basic respiratory rhythm and that this ventrolateral respiratory column (VRC) is profoundly influenced by the neurons of the pontine respiratory group (PRG). However, functional connectivity among PRG and VRC neurons is poorly understood. This study addressed four model-based hypotheses: 1) the respiratory modulation of PRG neuron populations reflects paucisynaptic actions of multiple VRC populations; 2) functional connections among PRG neurons shape and coordinate their respiratory-modulated activities; 3) the PRG acts on multiple VRC populations, contributing to phase-switching; and 4) neurons with no respiratory modulation located in close proximity to the VRC and PRG have widely distributed actions on respiratory-modulated cells. Two arrays of microelectrodes with individual depth adjustment were used to record sets of spike trains from a total of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Data were evaluated for respiratory modulation with respect to efferent phrenic motoneuron activity and short-timescale correlations indicative of paucisynaptic functional connectivity using cross-correlation analysis and the "gravity" method. Correlogram features were found for 109 (3%) of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG-PRG pairs, and 319 (7%) of the 4,340 VRC-VRC neuron pairs evaluated. Correlation linkage maps generated for the data support our four motivating hypotheses and suggest network mechanisms for proposed modulatory functions of the PRG.

Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network

“…A recent study of functional connectivity within this pontomedullary network supported model-based hypotheses on circuit mechanisms for pontine influences on respiratory phase switching and drive (Rybak et al 2008;Segers et al 2008). Multi-array electrode technology and spike train analysis have also identified correlational linkages that support a model of respiratory network architecture with raphé circuits serving as a parallel system of 'intermediate relays' between the VRC and PRG (Nuding et al 2009), as proposed by Bianchi et al (1995).…”

“…Chemoreception and brainstem circuits S. C. with permission of the University of Wisconsin Press, as described in Segers et al (2008).…”

Chronic intermittent hypoxia alters glutamatergic control of sympathetic and respiratory activities in the commissural NTS of rats

“…Therefore, we suggest that L-glutamate at the level of cNTS plays a critical role in the control of post-I activity and inspiratory off-switch in in situ preparations. The neuronal sources underlying the ionotropic glutamatergic control of respiratory activity at the level of the cNTS require further studies to be fully elucidated, but it may involve the respiratory neurons of dorsal respiratory column (17) and connections with Bötzinger complex (BötC) (19,55) and dorsolateral pons (33,51,53).…”

Optical analysis of circuitry for respiratory rhythm in isolated brainstem of foetal mice

“…Although much of our understanding of the functional circuitry of the mammalian brain has come from electrophysiological recordings with single electrodes (Long & Duffin 1986;Ezure 1990;Feldman et al 2003) and more recently with multi-electrode arrays (Lindsey et al 2000;Segers et al 2008), there is some question about the usefulness of recording respiratory rhythms from the hypoglossal nerve (St John et al 2004). Optical recording techniques have the obvious advantage that the activity of many neurons can be recorded at once, preserving the spatial distribution of the different cells (Potts & Paton 2006).…”