Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones to their roles in cardiorespiratory reflex integration: a whole cell recording study in situ

Key points Sympathetic preganglionic neurones (SPNs) gatekeep the activity flowing from the CNS to the periphery and their intrinsic properties are believed to play an important integrative role in determining the firing patterns. Previous cell recording studies have explored the electrophysiological characteristics of SPNs but until now it has not been possible to link this knowledge to their roles in cardiorespiratory integration. We used the working heart-brainstem preparation to make whole-cell patch clamp recordings from thoracic SPNs (n=98). The SPNs were classified into muscle vasoconstrictor-like (MVClike, 39%) and cutaneous vasoconstrictor-like (CVClike, 28%) on the basis of their dichotomous responses to cardiorespiratory reflex activation. The MVClike SPNs have higher baseline firing frequencies and distinctive intrinsic properties. Their firing is driven by a barrage of excitatory synaptic potentials with both tonic and respiratory modulated components. The CVClike SPNs show stereotyped rhythmical membrane potential oscillations that underpin their action potential discharge. We propose that these striking differences in the intrinsic properties of the classes of SPNs are likely to play an important role in patterning the sympathetic outflow. Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing from the CNS to the periphery to reach the target organs. Although previous in vivo and in vitro cell recording studies have explored their electrophysiological characteristics, it has not been possible to relate these characteristics to their roles in cardiorespiratory reflex integration. We used the working heart-brainstem preparation to make whole cell patch clamp recordings from T3-4 SPNs (n=98). These SPNs were classified by their distinct responses to activation of the peripheral chemoreflex, diving response and arterial baroreflex, allowing the discrimination of muscle vasoconstrictor-like (MVClike, 39%) from cutaneous vasoconstrictor-like (CVClike, 28%) SPNs. The MVClike SPNs have higher baseline firing frequencies (2.52 +/- 0.33Hz vs. CVClike 1.34 +/- 0.17Hz, P=0.007). The CVClike have longer after-hyperpolarisations (314 +/- 36ms vs. MVClike 191 +/- 13ms, P<0.001) and lower input resistance (346 +/- 49 M omega vs. MVClike 496 +/- 41M omega, P<0.05). MVClike firing was respiratory-modulated with peak discharge in the late inspiratory/early expiratory phase and this activity was generated by both a tonic and respiratory-modulated barrage of synaptic events that were blocked by intrathecal kynurenate. In contrast, the activity of CVClike SPNs was underpinned by rhythmical membrane potential oscillations suggestive of gap junctional coupling. Thus, we have related the intrinsic electrophysiological properties of two classes of SPNs in situ to their roles in cardiorespiratory reflex integration and have shown that they deploy different cellular mechanisms that are likely to influence how they integrate and shape the distinctive sympathetic outputs.