Studies conducted since the second half of the 19th century have revealed spontaneous as well as pharmacologically induced phasic/rhythmic discharge in spinal respiratory motor outputs of cats, dogs, rabbits, and neonatal rats following high cervical transection (Tx). The extent to which these various studies validate the existence of a true spinal respiratory rhythm generator remains debated. In this set of studies, we seek to characterize patterns of spontaneous phasic/rhythmic, asphyxia-induced, and pharmacologically induced activity occurring in phrenic nerve (PhN) discharge after complete high cervical (C1-C2) spinal cord transection. Experiments were performed on 20 unanesthetized decerebrate Sprague-Dawley adult male rats. Patterns of spontaneous activity after spinalization included tonic, phasic, slow oscillatory, and long-lasting tonic discharges. Topical application of antagonists of GABAA and glycine receptors to C1- and C2- spinal segments induced left-right synchronized phasic decrementing activity in PhN discharge that was abolished by an additional C2Tx. Asphyxia elicited increases in tonic activity and left-right synchronized gasp-like bursts in PhN discharge, demonstrating the presence of spinal circuits that may underlie a spinal gasping-like mechanism. We conclude that intrinsic slow oscillators and a phasic burst/rhythm generator exist in the spinal cord of the adult rat. If present in humans, this mechanism may be exploited to recover respiratory function in patients sustaining severe spinal cord injury.

Fast oscillations are ubiquitous throughout the mammalian central nervous system and are especially prominent in respiratory motor outputs, including the phrenic nerves (PhNs). Some investigators have argued for an epiphenomenological basis for PhN high-frequency oscillations because phrenic motoneurons (PhMNs) firing at these same frequencies have never been recorded, although their existence has never been tested systematically. Experiments were performed on 18 paralyzed, unanesthetized, decerebrate adult rats in which whole PhN and individual PhMN activity were recorded. A novel method for evaluating unit-nerve time-frequency coherence was applied to PhMN and PhN recordings. PhMNs were classified according to their maximal firing rate as high, medium, and low frequency, corresponding to the analogous bands in PhN spectra. For the first time, we report the existence of PhMNs firing at rates corresponding to high-frequency oscillations during eupneic motor output. The majority of PhMNs fired only during inspiration, but a small subpopulation possessed tonic activity throughout all phases of respiration. Significant time-varying PhMN-PhN coherence was observed for all PhMN classes. High-frequency, early-recruited units had significantly more consistent onset times than low-frequency, early/middle-recruited and medium-frequency, middle/late-recruited PhMNs. High- and medium-frequency PhMNs had significantly more consistent offset times than low-frequency units. This suggests that startup and termination of PhMNs with higher firing rates are more precisely controlled, which may contribute to the greater PhMN-PhN coherence at the beginning and end of inspiration. Our findings provide evidence that near-synchronous discharge of PhMNs firing at high rates may underlie fast oscillations in PhN discharge.

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The PED may be used successfully to treat select aneurysms of the PICA. We present the first described cases of successful PED treatment of PICA aneurysms with direct placement of the PED in the PICA vessel itself. The proposed classification system aids in that selection.

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While supraspinal mechanisms underlying respiratory pattern formation are well characterized, the contribution of spinal circuitry to the same remains poorly understood. In this study, we tested the hypothesis that intraspinal GABAergic circuits are involved in shaping phrenic motor output. To this end, we performed bilateral phrenic nerve recordings in anesthetized adult rats and observed neurogram changes in response to knocking down expression of both isoforms (65 and 67 kDa) of glutamate decarboxylase (GAD65/67) using microinjections of anti-GAD65/67 short-interference RNA (siRNA) in the phrenic nucleus. The number of GAD65/67-positive cells was drastically reduced on the side of siRNA microinjections, especially in the lateral aspects of Rexed's laminae VII and IX in the ventral horn of cervical segment C4, but not contralateral to microinjections. We hypothesize that intraspinal GABAergic control of phrenic output is primarily phasic, but also plays an important role in tonic regulation of phrenic discharge. Also, we identified respiration-modulated GABAergic interneurons (both inspiratory and expiratory) located slightly dorsal to the phrenic nucleus. Our data provide the first direct evidence for the existence of intraspinal GABAergic circuits contributing to the formation of phrenic output. The physiological role of local intraspinal inhibition, independent of descending direct bulbospinal control, is discussed.

: Although medullary control of blood pressure (BP) has been extensively studied, the contribution of critical regions, such as pressor sites in the caudal medulla and upper cervical spinal cord and the lateral tegmental field, remains controversial and underappreciated. A series of pressor sites caudal to the caudal ventrolateral medulla (CVLM), including the caudal pressor area (CPA) and medullocervical pressor area, play an important role in control of BP. Activation and inhibition of these sites elicits pressor and depressor responses, respectively. Basal sympathetic tone is provided principally by the medullary lateral tegmental field and rostral ventrolateral medulla (RVLM). RVLM presympathetic neurons, which project to and drive preganglionic sympathetic somata in the intermediolateral cell column, are powerfully regulated by neurons in CVLM via tonic and phasic inhibition. The current state of knowledge is summarized thus: rostrocaudally organized columns of pressor sites caudal to CVLM extend to the upper cervical spinal cord; CPA pressor responses are RVLM-dependent; CPA mediates pressor responses by (first) inhibiting RVLM-projecting inhibitory CVLM units and (second) activating RVLM-projecting excitatory CVLM units; the chemoreflex is CPA-dependent; the baroreflex is CPA-independent; pressor responses to raphe obscurus stimulation are CPA-dependent; and medullocervical pressor area pressor responses are RVLM-independent, likely mediated by direct projections to the intermediolateral cell column. In this review, we seek to underscore and characterize the critical role played by the caudal medulla and upper cervical spinal cord in BP regulation and highlight important gaps in knowledge in interactions between the caudal medulla and other regions controlling BP, which may prove critical in revealing central mechanisms underlying pathophysiology of, and pharmacotherapeutic targets for, hypertension.

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