Non-technical summary The brain controls the heart through parasympathetic (vagal) and sympathetic nerves. Vagal control is integral to cardiac health and a loss of vagal tone is a poor prognostic sign in cardiovascular diseases such as heart failure and hypertension. The vagal drive to the heart is transmitted across synapses located in the cardiac ganglia on the heart. We have developed a novel methodology to make intracellular recordings from cardiac ganglion neurones on the surface of the beating heart in a preparation with intact functional drive from the brainstem. We show how these neurones process their synaptic inputs and demonstrate that the ganglion plays a key role in regulating the level of vagal tone reaching the heart. This identifies the cardiac ganglion as a viable target for interventions to restore the transmission of vagal tone in cardiovascular diseases.Abstract Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmission in vivo are poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart-brainstem preparation. The atria were stabilised in situ preserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart. Abbreviations: AHP, after-hyperpolarisation; HR, heart rate; PNA, phrenic nerve activity; PP, perfusion pressure; SAH, slow after-hyperpolarisation; V m , membrane potential; WHBP, working heart-brainstem preparation.

Torsional loads are ubiquitous during everyday dextrous manipulations. We examined how information about torque is provided to the sensorimotor control system by populations of tactile afferents. Torsional loads of different magnitudes were applied in clockwise and anticlockwise directions to a standard central site on the fingertip. Three different background levels of contact (grip) force were used. The median nerve was exposed in anaesthetized monkeys and single unit responses recorded from 66 slowly adapting type-I (SA-I) and 31 fast adapting type-I (FA-I) afferents innervating the distal segments of the fingertips. Most afferents were excited by torque but some were suppressed. Responses of the majority of both afferent types were scaled by torque magnitude applied in one or other direction, with the majority of FA-I afferent responses and about half of SA-I afferent responses scaled in both directions. Torque direction affected responses in both afferent types, but more so for the SA-I afferents. Latencies of the first spike in FA-I afferent responses depended on the parameters of the torque. We used a Parzen window classifier to assess the capacity of the SA-I and FA-I afferent populations to discriminate, concurrently and in real-time, the three stimulus parameters, namely background normal force, torque magnitude and direction. Despite the potentially confounding interactions between stimulus parameters, both the SA-I and the FA-I populations could extract torque magnitude accurately. The FA-I afferents signalled torque magnitude earlier than did the SA-I afferents, but torque direction was extracted more rapidly and more accurately by the SA-I afferent population.

When humans manipulate objects, the sensorimotor system coordinates three-dimensional forces to optimize and maintain grasp stability. To do this, the CNS requires precise information about the magnitude and direction of load force (tangential to skin surface) plus feedback about grip force (normal to skin). Previous studies have shown that there is rapid, precise coordination between grip and load forces that deteriorates with digital nerve block. Obviously, mechanoreceptive afferents innervating fingerpad skin contribute essential information. We quantify human capacity to scale tangential and normal forces using only cutaneous information. Our paradigm simulated natural manipulations (a force tangential to the skin superimposed on an indenting force normal to the skin). Precisely controlled forces were applied by a custom-built stimulator to an immobilized fingerpad. Using magnitude estimation, subjects (n ϭ 8) scaled the magnitude of tangential force (0.25-2.8 N) in two experiments (normal force, 2.5 and 4 N, respectively). Performance was unaffected by normal force magnitude and tangential force direction. Moreover, when both normal (2-4 N) and tangential forces were varied in a randomized-block factorial design, the relationship between applied and perceived tangential force remained near linear, with a minor but statistically significant nonlinearity. Our subjects could also discriminate small differences in tangential force, and this was the case for two different reference stimuli. In both cases, the Weber fraction was 0.16. Finally, scaling functions for magnitude estimates of normal force (1-5 N) were also approximately linear. These data show that the cutaneous afferents provide a wealth of precise information about both normal and tangential force.

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.

1. The idea is introduced that cardiac rate, contractility or atrioventricular (A-V) conduction spread may be controlled independently by the brain. Limited data from reflex studies are cited to support this view. 2. Evidence is presented that individual autonomic post- and preganglionic neurons have quite specific actions on the heart. Premotor and other central neurons can have preferential actions on heart rate, contractility or A-V conduction. 3. The functional implications of selective cardiac control are discussed.