Bulbar respiratory neurons participating in the sniff reflex in the cat

Activity of bulbar respiratory neurons was recorded extracellularly in anesthetized cats in which sniffs were induced by mechanical stimulation of the nasopharyngeal mucosa during the expiratory pause. Sniffs were indicated by brief, rapid activation of the diaphragmatic EMG which was followed by a sharp rise of tracheal inspiratory airflow (aspiration reflex of Tomori). In large sniffs, inspiratory neurons were activated in highfrequency bursts which preceded diaphragmatic activation. Other neurons in the bulbar reticular formation did not exhibit these properties. Inspiratory neurons located ipsilateral to the stimulated nasopharynx in the region ventrolateral to fasciculus solitarius exhibited low-threshold bursting and the earliest activation. The same neurons responded weakly and late to stimulation of the contralateral nasopharynx. Inspiratory neurons located in the environs of nucleus ambiguus frequently failed to participate in weaker sniffs, but a few always participated. Most neurons in this region were activated at nearly equal times before the diaphragm whether ipsilateral or contralateral nasopharynx was stimulated. Expiratory neurons located bilaterally near nucleus ambiguus were inhibited in numbers and in degree which matched the magnitude of the sniff. Weaker sniffs were accompanied by inhibition of late expiratory units alone, while stronger sniffs involved all expiratory neurons. Repeated stimulations could silence the expiratory units for long periods.     

An anomalous vagorenal reflex pathway in the cat

Although physiological investigations support the view that the innervation to the kidney is primarily sympathetic in origin, there is anatomic evidence suggesting direct vagal projections to the kidney. We examined electrophysiologically the possibility that neural connections exist between the cervical vagus and renal nerves. Electrical stimulation of the peripheral segment of the cut cervical vagus evoked electrical activity in the central segment of cut renal nerve of chloralose-anesthetized, paralyzed cats. The evoked potentials (vagorenal responses) displayed components with peak latencies of about 50, 120, and 500 ms. Another peak at about 175 ms was also seen in some cases. In addition, a period of postexcitatory depression occurred between approximately 180 and 400 ms after delivery of the stimulus. Evoked responses were recorded in the contralateral as well as the ipsilateral renal nerves. In contrast, stimulation of the central cut end of renal nerves did not elicit responses in the cervical vagus. Vagorenal responses were not altered by cutting the subdiaphragmatic vagus indicating that the abdominal vagus was not involved in this response. Electrical activity in renal nerves elicited by vagal stimulation could be eliminated by either ganglionic blockade or by cutting or cooling the splanchnic nerves. Finally, supraspinal ischemia abolished the vagorenal response. These data suggest that a vagorenal reflex pathway exists and that the potentials recorded in renal nerves are due to activation of aberrant sensory fibers traveling from the peripheral segment of the cut cervical vagus to the central nervous system, where they excite a sympathetic efferent pathway to the kidney.     

Sympathetic nerve activity restrains reflex vasodilatation in heart failure

Background Blunted reflex muscle vasodilatory response during exercise in heart failure (HF) patients may be secondary to augmented vasoconstriction. We tested the hypothesis that the exaggerated sympathetic nerve activity restrains the reflex muscle vasodilatation during exercise in HF patients. Methods We studied the reflex vasodilatory response (plethysmography) during 3 min static handgrip exercise at 30% maximal voluntary contraction in 10 advanced HF patients (45 ± 3year, NYHA Functional Class III/IV) and 10 age-matched normal controls (NC, 40 ± 3year, P = 0.23) during intra-arterial infusion of: (1) saline control; and (2) alpha-adrenergic blocker (phentolamine). Results Baseline forearm vascular conductance (FVC) was lower in HF patients than in NC (2.07 ± 0.2 vs. 4.26 ± 0.6 units, respectively; P = 0.002). FVC responses during exercise increased significantly in NC, but not in HF patients (delta changes: 1.05 ± 0.4 vs. 0.05 ± 0.2 units, respectively). Phentolamine significantly increased resting FVC in HF patients (from 2.07 ± 0.2 to 5.74 ± 0.7 units, P = 0.00004) and restored reflex vasodilatory responses during exercise (delta changes: from 0.05 ± 0.2 to 1.82 ± 0.9 units) eliminating the difference in FVC between both groups. Conclusions The blunted reflex muscle vasodilatory response during exercise in advanced HF patients is, at least in part, due to the increase in sympathetic nerve activity.     

Bulbar reticular unit activity during food ingestion in the cat

During food ingestion in cats, the activity of single bulbar reticular neurons showed rhythmical spike bursts during the active jaw opening phase of mastication. By utilizing spike-triggered averaging techniques, certain reticular cells were strongly suggested to be inhibitory neurons projecting to jaw closer motoneurons. We propose that these bulbar reticular neurons participate in the central generation of masticatory jaw movements by rhythmically inhibiting jaw closer motoneurons during mastication.     

Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat

The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 μs pulses at 50 Hz intratrain frequencies, 300–500 ms trains, 0.5–15 V) in the region of the locus coeruleus (P 0.5–3.1/L 2–4/H to −2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 ± 11cm H₂O, 10 ± 3s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 ± 29cm H₂O, 70 ± 44s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L₇-S₃ dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.     

Physiologic and anatomic basis for contralateral R1 in blink reflex

We studied the rate of appearance and mechanism of contralateral R1 responses in normal subjects. Contralateral R1 could be produced by facilitating maneuvers such as a gentle contraction of the orbicularis oculi and conditioning stimulus of the median nerve. In addition, changing the position of the stimulating anode to the midline evoked these responses that were abolished by blocking the contralateral supraorbital nerve, confirming its peripheral origin. We conclude that crossed trigeminofacial pathways probably exist in normal subjects, but in some instances contralateral peripheral trigeminal ophthalmic sensory fibers may be stimulated, giving rise to a contralateral R1 response.     

Neurogenic forearm vasodilatation during contralateral isometric exercise is attenuated in diabetes mellitus

The responses in heart rate, blood pressure and blood flow in the resting forearm during contralateral isometric handgrip were investigated together with the respiratory sinus arrhythmia (measured during standardized breathing frequency and depth), and the heart rate response to a Valsalva manoeuvre in 20 patients with insulin-dependent diabetes and clinical signs of a peripheral neuropathy. The respiratory sinus arrhythmia and the Valsalva ratio were attenuated in the patients compared to age-matched controls, indicating reduced vagal function. Also the responses to handgrip were reduced. The blood flow increase in the resting forearm upon handgrip was correlated with both the respiratory sinus arrhythmia and the Valsalva ratio, supporting neurogenic mediation of the flow response and indicating a reduction in sympathetic as well as vagal function in diabetes autonomic neuropathy.     

Anatomical and physiological study of interneurons in an oligosynaptic cutaneous reflex pathway in the cat hindlimb.

Morphological and physiological studies were undertaken in the cat lumbosacral spinal cord in order to examine individual last-order excitatory interneurons in the disynaptic pathway between low threshold superficial peroneal (SP) afferents and flexor digitorum longus (FDL) motoneurons. Last-order interneurons projecting to the FDL motor nucleus were visualized with activity-dependent trans-synaptic transport of lectin-conjugated horseradish peroxidase (WGA-HRP). The location of lumbar interneurons that responded at short latencies (less than 3 ms) to electrical stimulation of the SP nerve was further defined using extracellular recording. The projection of individual interneurons to motoneurons in the L6 segment was defined by spike-triggered averaging of population ventral root potentials (VRPs) using the sucrose gap technique. Measurements of the central latencies from the arrival of the SP afferent volley to interneuron firing, and from interneuron spike to the onset of the VRP EPSPs, confirm the existence of a low threshold, disynaptic SP pathway that excited motoneurons. These data provide useful latency constraints for the interpretation of the synaptic length of cutaneous reflex pathways in the cat hindlimb.     

Ipsilateral motor pathway without contralateral motor pathway in a stroke patient

The ipsilateral motor pathway from the unaffected motor cortex to the affected extremity is one of the mechanisms of motor recovery following stroke. We report on a stroke patient who showed the ipsilateral motor pathway without the contralateral motor pathway on functional MRI and diffusion tensor tractography. A 53-year-old left hemiparetic patient with an infarct in the right middle cerebral artery territory was evaluated. During a period of three months after onset, motor function of the affected (left) hand had recovered slowly, to the extent that the patient was able to overcome gravity. FMRI showed that only the unaffected (left) primary sensorimotor cortex was activated by movements of the unaffected (right) hand or of the affected (left) hand. On diffusion tensor tractography, the corticospinal tract of the left hemisphere originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway. By contrast, the right corticospinal tract showed a disruption with Wallerian degeneration to the upper medulla. We conclude that the motor function of the affected (left) hand appeared to be controlled only by the ipsilateral motor pathway from the left motor cortex to the left hand. Motor function of the affected hand appeared to have been reorganized to the ipsilateral motor pathway from the unaffected motor cortex to the affected hand.     

Adaptive fusimotor reflex control in the decerebrate cat

The effect of electrical stimulation of cutaneous afferents in the superficial peroneal nerve on the locomotor discharges of single medial gastrocnemius gamma-motoneurones has been investigated in a decerebrate cat preparation. Units were classified as static (n=9) or dynamic (n=7) indirectly on the basis of their resting and locomotor discharge characteristics. Brief trains of stimulation, at 2 and 3xthreshold (T), were applied at rest and during locomotion. Responses were assessed by calculating the change in mean rate during the 100 ms after stimulus onset compared with a control period. At rest, static and dynamic gamma-motoneurones showed opposite responses. Static neurones were excited while inhibition was dominant with dynamic neurones. Effects were always present at 2T. During locomotion, inhibitory responses occurred with both types of gamma-motoneurone and excitation was not apparent. The inhibition of static neurones was maximum during (four units) or between (five units) EMG bursts and minimum in the opposite phase of EMG activity. For dynamic neurones, inhibition was not related to locomotor phase. Generally (six of seven units), the inhibition of dynamic gamma-motoneurones was reduced throughout the step cycle, including phases in which background discharge rates were comparable to resting levels. Latencies of response were measured from peristimulus time histograms. Subtraction of peripheral conduction times gave estimated central delays of locomotor inhibition for static (2.4+/-0.2 ms, n=6; mean+/-S.E.M.) and dynamic (2.2+/-0.2 ms, n=7) gamma-motoneurones that were not significantly different (P>0. 1) and are consistent with spinal oligosynaptic pathways. We conclude that low threshold skin afferents from the foot dorsum are capable of influencing both types of gamma-motoneurone during walking through short latency spinal inhibitory pathways. Further, a highly specific (reciprocal) control of the reflex responses of static and dynamic gamma-efferents occurs that is dependent upon behavioural context. The results are discussed in relation to cutaneous effects on gamma-motoneurones which are suggested to form an adaptive control system.     

Neural mechanisms controlling jaw-jerk reflex in the cat

Signal substances of axon terminals presynaptic to jaw spindle Ia afferents and their ultrastructural features were examined using a combination of intra-axonal horseradish peroxidase injection and postembedding immunogold-labeling techniques in cats. A total of 35 axon terminals presynaptic to 22 horseradish peroxidase-labeled Ia boutons were examined. Of the 35 presynaptic axon terminals, 14 (40%) were immunoreactive for both gamma-aminobutyric acid and glycine, 9 (26%) for gamma-aminobutyric acid alone and 9 (26%) for glycine alone. The bouton volume, mitochondrial volume, active zone area, and apposed surface area were larger for Ia boutons than for presynaptic axon terminals, while each of the values is similar among the three types of presynaptic axon terminals. These results suggest that gamma-aminobutyric acid and glycine play an important role for modulating the jaw-jerk reflex presynaptically and that the smaller size of presynaptic axon terminals is important to prevent action potential generation from Ia afferents.     

Anatomical evidence for two spinal 'afferent-interneuron-efferent' reflex pathways involved in micturition in the rat: a 'pelvic nerve' reflex pathway and a 'sacrolumbar intersegmental' reflex pathway

We labeled interneurons in the L1-L2 and L6-S1 spinal cord segments of the rat that are involved in bladder innervation using transneuronal retrograde transport of pseudorabies virus (PRV) in normal animals and in animals with selected nerve transections. Preganglionic neurons were identified using antisera against choline acetyltransferase (ChAT). In some experiments we labelled parasympathetic preganglionic neurons (PPNs) in the L6-S1 spinal cord by retrograde transport of Fluorogold from the major pelvic ganglion. We identified bladder afferent terminals using the transganglionic transport of the anterograde tracer cholera toxin subunit b. We present anatomical evidence for two spinal pathways involved in innervation of the bladder. First, in the intact rat, afferent information from the bladder connects, via interneurons in L6-S1, to the PPNs that provide the efferent innervation of the bladder. The afferent terminals were located mainly in close apposition to interneurons located dorsal to the retrogradely labeled PPNs. Second, using L6-S1 ganglionectomies or L6-S1 ventral root rhizotomies we limited viral transport to the sympathetic pathways innervating the bladder. This procedure also labelled interneurons (but not PPNs) with PRV in the L6-S1 spinal cord in a location very similar to those described in the intact rat. These interneurons also receive bladder afferent terminals but we propose that they project to sympathetic preganglionic neurons, most of which are in the L1-L2 spinal segments. Based on this anatomical evidence, we propose the existence of two spinal reflex pathways involved in micturition: a pathway limited to a reflex arc in the pelvic nerve (presumably excitatory to the detrusor muscle); and a pathway involving the pelvic nerve and sympathetic nerve fibers, some of which may travel in the hypogastric (presumably inhibitory to the detrusor muscle).     

Sensorimotor transformation in cat nociceptive withdrawal reflex system

The withdrawal reflex system of higher vertebrates has been extensively used as a model for spinal sensorimotor integration, nociceptive processing and plasticity. In the rat, the nociceptive withdrawal reflex system appears to have a modular organization. Each reflex module controls a single muscle or a few synergistic muscles, and its cutaneous receptive field corresponds to the skin area withdrawn upon contraction of the effector muscle(s) when the limb is in the standing position. This organization principle is at odds with the 'flexion reflex' concept postulated from cat studies. To assess the generality of the modular organization principle we have therefore re-examined the cutaneous input to the withdrawal reflex system of the cat. The cutaneous receptive fields of hindlimb and forelimb muscles were mapped using calibrated noxious pinch stimulation and electromyographic recording technique in barbiturate anaesthetized animals. The investigated muscles had specific cutaneous receptive fields that appeared to correspond to the area of the skin withdrawn upon contraction of the muscle when the limb is in the standing position. The spatial organization of receptive fields in the cat was similar to that in the rat. However, differences in gain properties of reflexes to some anatomically equivalent muscles in the two species were observed, possibly reflecting adaptations to the biomechanics characteristic of the digitigrade and plantigrade stance in cats and rats, respectively. Implications of the findings for the generality of the modular organization of the withdrawal reflex system and for its adaptive properties are discussed.     

Visual pathway for the optokinetic reflex in infant macaque monkeys

The horizontal optokinetic nystagmus (hOKN) in primates is immature at birth. To elucidate the early functional state of the visual pathway for hOKN, retinal slip neurons were recorded in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of 4 anesthetized infant macaques. These neurons were direction selective for ipsiversive stimulus movement shortly after birth [postnatal day 9 (P9)], although at a lower direction selectivity index (DSI). The DSI in the older infants (P12, P14, P60) was not different from adults. A total of 96% of NOT-DTN neurons in P9, P12, and P14 were binocular, however, significantly more often dominated by the contralateral eye than in adults. Already in the youngest animals, NOT-DTN neurons were well tuned to different stimulus velocities; however, tuning was truncated toward lower stimulus velocities when compared with adults. As early as at P12, electrical stimulation in V1 elicited orthodromic responses in the NOT-DTN. However, the incidence of activated neurons was much lower in infants (40-60% of the tested NOT-DTN neurons) than in adults (97%). Orthodromic latencies from V1 were significantly longer in P12-P14 (x = 12.2 ± 8.9 ms) than in adults (x = 3.51 ± 0.81 ms). At the same age, electrical stimulation in motion-sensitive area MT was more efficient in activating NOT-DTN neurons (80% of the tested cells) and yielded shorter latencies than in V1 (x = 7.8 ± 3.02 ms; adult x = 2.99 ± 0.85 ms). The differences in discharge rate between neurons in the NOT-DTN contra- and ipsilateral to the stimulated eye are equivalent to the gain asymmetry between monocularly elicited OKN in temporonasal and nasotemporal direction at the various ages.     

The peripheral pathway for extracranial vasodilatition in the cat

The locus coeruleus was electrically stimulated in 27 cats with high spinal cord sections. Common carotid blood flow was measured using electromagnetic flow probes, and arterial resistance calculated from mean arterial blood pressure and flow. Activation of the locus coeruleus caused an ipsilateral decrease in common carotid resistance, an effect previously demonstrated to depend on the integrity of the facial nerve. This vasodilator response is now shown to be mediated approximately equally by the pterygopalatine (sphenopalatine) and otic ganglia.