Direct neuronal recordings from structures involved in cardiovascular regulation in freely moving animals are almost nonexistent. Rhythmic single neuron firing synchronized with blood pressure and/or sympathetic nerve oscillations have been demonstrated in a number of central nuclei but with a few exceptions all these studies used anesthetized animals. In the past decade, the enormous progress in technology revolutionalized the functional investigations of neuronal ensembles in unanesthetized animals. Advances in miniature headstages, complex microelectrode assemblies, and in powerful methods of multichannel data analysis made possible simultaneous recording and analysis of >100 neurons in natural behaviors. To date these advances, however, have not reached autonomic neuroscience most likely due to skepticism of the possibility of microwire recordings (1) in deep structures and (2) in caudal locations of the brainstem (in the medulla in particular). Thus, in the present study neuronal recordings have been performed in 5 unanesthetized rats using multiple microwires. Electrocardiogram (ECG) and hippocampal field potentials were recorded simultaneously in each rat, with neck muscle electromyogram in two, to allow assessment of the sleep-wake state of the animal. The electrodes were implanted under anesthesia (mixture of Ketamine and Xylasine; 40 and 5 mg/kg body weight). Simultaneous recordings of multiple single neurons were obtained using tetrode electrodes aimed at central autonomic structures in the medulla, primarily in the rostral ventrolateral medulla (RVLM) and in surrounding structures located dorsal to this nucleus. Periodic modulations of neuronal discharges were assessed by calculating the firing probability relative to the ECG R-waves using spike triggered averages. Respiratory rhythm was also derived from the ECG by identifying periodically occurring bradycardic episodes (respiratory sinus arrhythmia). Three tetrodes (12 microwires) were used which allowed simultaneous recording of 4 to 35 neurons for 10 to 50 min. We found that neurons located in close vicinity to each other exhibited different levels of coupling with cardiorespiratory oscillations. Several discharge patterns were found in simultaneous recordings of different neurons, including cardiac rhythmicity, respiratory rhythmicity, or patterns in which cardiac-related modulation was periodically enhanced at specific phases of the respiratory cycle. The variety of discharge patterns of simultaneously recorded neurons in regard of their coupling with respiratory and cardiac rhythms. The coupling between R-waves and neuronal discharge outside the RVLM was intermittent and showed slipping of the relative phase indicating relative coordination and was frequently modulated by the level of vigilance. Sleep-related slowing of neuronal discharge was often associated with shifts in the R-wave – neuron frequency ratio.