Insights gleaned from pharmaco‐genetic dissection and modelling of cardio‐respiratory neural networks (2015)

This special issue consists of a series of papers based on presentations from a sym-posium we organised at the Experim-ental Biology meeting in 2014, San Diego, CA, USA, entitled ‘Insights gleaned from pharmaco-genetic dissection and modelling of cardio-respiratory neural networks’. This symposium followed two symposia we previously chaired in 2003 (‘Identifying genes and targets in cardiovascular autonomic pathophysiological states’) and 2008 (‘Smarter targeting of genes for cardiovascular genomics’). Our vision for these previous symposia and indeed the current one presented here was to showcase contemporary science with the very latest experimental technology. To this end we asked four speakers to demonstrate how rapidly changing technology is pushing their research into unexplored areas. Below we provide the original titles of these talks and a brief synopsis of what the papers report. First, Dr Abdala presented ‘Defining a role for glycinergic inhibition within the respiratory network using optogenetics’. Her article reviews the role of fast inhib-itory synaptic transmission for generation of a physiological respiratory pattern, while discussing some of the opportunities provided by emerging optogenetic approaches as high-resolution functional analysis tools of genotypically identified inhibitory respiratory neurones. It offers the reader helpful insight on merits and limitations of this new technology, especially in regard of the unique challenges provided by the respiratory circuitry (Abdala et al. 2015). Second, Dr Bub's presentation was entitled ‘Macro-micro imaging of cardiac-neural circuits in co-cultures from normal and diseased hearts’. A variety of life threatening cardiac arrhythmias have been attributed to formation of large scale patterns of excitation such as the formation and break up of spiral waves. These may be initiated by stimulation of myocytes by sympathetic neurons. An understa-nding of arrhythmogenesis can depend on measurement of complex activation patterns, which require methods for recording activity over long time periods. Optical mapping techniques, based on imaging fluorescence from voltage or ion sensitive dyes using fast cameras have emerged as vital tools for elucidating arrhythmogenic mechanisms at the organ and tissue levels. Gil Bub and Rebecca Burton (Bub & Burton, 2015) present their recent work on developing a simplified in vitro cell-culture model of neurally mediated arrhythmogenesis using dye-free high-speed optical mapping methods. This imaging technique allows us to measure experimentally important cardiac parameters at high speeds and simultaneously measure fine structural detail to relate structure and function. Additionally, this imaging modality also allows the investigator to utilise optogenetic tools to allow specific perturbations of different cells. Third, Dr David Moraes (Moraes et al. 2015) spoke on ‘Brainstem channelopathy of neurogenic hypertension’. A novel idea was presented showing that sympathetic overactivity in rodent models of neurogenic hypertension is dependent on alterations in the electrical excitability of medullary respiratory neurones that modulate sympatho-excitatory networks. The current dogma of increased excitability of pre-motor sympathetic neurones in neurogenic hypertension was therefore contested. Also presented were new data showing that the changes in the medullary respiratory neurone excitability were due to changes in ion channel expression – so-called ‘respiratory neurone channelopathy of hypertension’. The latter was dependent on carotid body input supporting the notion of targeting the carotid body as a potential novel therapeutic strategy for controlling hypertension. Finally, Dr Osborn presented a talk on ‘A new computational model for mechanisms of salt sensitive hypertension: a role for the sympathetic nervous system’. The causes of salt-sensitive hypertension are complex and mathematical models can elucidate potential mechanisms. The previous model of Guyton and Coleman was used to explain long-term control of arterial pressure. This classic model makes the assumption that sodium excretion is driven by renal perfusion pressure and that all forms of hypertension are due to a shift of the renal function curve to a higher operating pressure. Based on experimental data from numerous rodent models and development of a new mathematical model, which they term the ‘neurogenic model’, Osborn et al. (2015) re-examined the Guyton and Coleman model. This report discusses that salt-sensitive hypertension does not have to be due solely to renal dysfunction, as the Guyton–Coleman model predicts but could also result from sympathetic activation to the kidney.