The sympathoexcitatory response following selective activation of a spinal cholinergic system in anesthetized rats

This study was performed to help elucidate the role of spinal cholinergic neurons in cardiorespiratory function by selective activation of spinal or medullary cholinergic systems in anesthetized rats. A selective site of action of cholinergic drugs on the spinal cord was obtained by refining the method of intrathecal (i.t.) drug injection to localize drug distribution to specific spinal segments. I.t. injection of the cholinesterase (ChE) inhibitor, neostigmine (NEO), produced a significant reduction in spinal, but not medullary tissue levels of ChE, and evoked marked pressor and tachycardic responses without any changes in respiratory parameters. In contrast to i.t. injection, intracisternal (i.c.) injection of NEO which inhibited both spinal and medullary ChE, produced characteristic respiratory changes--increased tidal volume and decreased respiratory rate and minute volume, as well as pressor and tachycardic responses. I.t. injection of the muscarinic antagonist, methylatropine, inhibited the cardiovascular responses to i.t. NEO, but not the cardiorespiratory responses to i.c. NEO. These cardiovascular responses to i.t. NEO were blocked by spinal transection, but not by midcollicular transection. Finally, the pressor and tachycardic responses to i.t. NEO were inhibited following peripheral alpha-adrenergic and beta-adrenergic blockade, respectively. These results indicate that activation of the spinal cholinergic system selectively produces a sympathoexcitatory response through spinal muscarinic receptor activation independent of respiratory changes. This finding is consistent with the possibility that such responses are elicited by activation of a non-cholinergic bulbo-spinal sympathoexcitatory pathway at the spinal level, or at higher centers through an ascending pathway. In either case, the spinal cholinergic system appears to be anatomically and pharmacologically distinct from the medullary pathway and may subserve a different function.     

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.     

The pressor response to spinal cholinergic stimulation in spontaneously hypertensive rats

Several laboratories have demonstrated that central cholinergic stimulation in spontaneously hypertensive rats (SHR) results in an exaggerated pressor response as compared to normotensive (NT) controls. Recent studies in this laboratory have demonstrated a spinal cholinergic pressor system in the NT rat. The purpose of this study was to determine whether the pressor response to spinal cholinergic stimulation is enhanced in SHR. In freely moving rats, intrathecal injection of neostigmine or carbachol (1-5 micrograms) produced a dose-related hypertensive response in both strains of rats. While both agonists produced similar maximal increases in blood pressure in NT rats, the pressor responses to both agonists were significantly greater in SHR. The tachycardic responses to IT injection of cholinergic agonists were also significantly greater in SHR. These differences were more apparent at the lower doses where, for example, the pressor response to 1 microgram of agonist in the SHR was increased by 123% and 109% of the response in NT rats for carbachol and neostigmine, respectively. Since both direct and indirect acting agonists produced greater responses in SHR, and spinal depletion of acetylcholine did not reduce blood pressure in SHR, it is most likely that spinal cholinergic systems ascend to higher centers to elicit pressor responses. In the case of the SHR, these higher centers may be supersensitive to cholinergic stimulation.     

Reflexes of the external urethral sphincter in children

The electromyographic responses in the external urethral sphincter to electrical stimulation of the pudendal nerve and stretch of the external sphincter were analyzed in a pediatric population; the population included a group with recurrent urinary tract infections and a group with complete or almost complete upper spinal cord lesions. Electrical stimulation produced a response of reflex nature mediated in the sacral spinal cord, frequently beginning with two components that could be individually characterized and that behaved similarly to a flexor reflex. The response produced by stretch appeared to be similar to that produced by electrical stimulation.     

Responses of sympathetic postganglionic neurons to peripheral nerve stimulation in pigeon (Columba livia).

Reflex changes in heart rate and arterial blood pressure can be elicited in pigeons with high cervical transection by stimulation of brachial or lumbosacral peripheral and spinal nerves. This extends the phenomenon of spinally mediated, somatosympathetic reflexes to another vertebrate class. In a preliminary attempt to explore the spinal circuitry mediating these reflexes, the responses of single sympathetic postganglionic neurons were studied during spinal and peripheral nerve stimulation. With stimulation and recording at the same spinal segment, calculation of the central delay suggests the segmental reflex circuitry may be relatively simple, possibly trisynaptic. As the distance between stimulating and recording sites increases, postganglionic neuronal responsiveness decreases and becomes more variable. However, there is clear evidence that lumbosacral afferents can activate postganglionic neurons at brachial levels, indicating an effective propriospinal circuitry for somatosympathetic reflexes. Experiments on birds with intact spinal cords demonstrate that these spino-spinal pathways are also functional in the intact animal. While the segmental reflex is not different in the intact bird, the propriospinal pathways do behave somewhat differently, possible suggesting tonic central control.     

Penile erection in the rat: stimulation of the hypogastric nerve elicits increases in penile pressure after chronic interruption of the sacral parasympathetic outflow

Penile erection, a vascular event mediated by the autonomic nervous system, is often adversely affected by injury to the spinal cord. To further characterize the laboratory rat as an animal model of penile erection and to investigate erectile responses following neural injury, the present study has examined pressor penile responses in intact rats and in animals deprived of sacral parasympathetic outflow. Increases in penile pressure result from graded stimulation of postganglionic parasympathetic fibers. The vasodilator response is insensitive to blockade with atropine, a cholinergic antagonist. Penile tumescence also results from stimulation of the pelvic nerve, but not the hypogastric nerve. However, beginning 3 days after unilateral interruption of the pelvic nerve, stimulation of the ipsilateral hypogastric nerve results in an increase in penile pressure. This novel response, which is blocked by a ganglionic antagonist, is maximally developed at 1 week post-lesion, is stable for at least 3 months and remains confined to the side of the lesion. These results suggest that the rat, although relatively small, can be used to obtain quantitative data on penile erection. Moreover, the model may lend itself to an analysis of the mechanisms of altered control of visceral tissues following injury to the nervous system.     

Spinal cholinergic and monoaminergic receptors mediate descending inhibition from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat

Focal electrical stimulation and glutamate microinjection in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) both inhibit the nociceptive tail-flick (TF) reflex in rats. The present experiments were undertaken to determine the transmitter(s) at the level of the lumbar spinal cord mediating descending inhibition of the TF reflex produced by activation of the NGC/NGC alpha. Intrathecal administration of atropine (7.2-57.6 nmol) produced a dose-dependent increase in the electrical stimulation threshold required for inhibition of the TF reflex. Phentolamine (47.2 or 94.4 nmol) and methysergide (32 or 64 nmol) also increased the stimulation threshold significantly, but only at the greater doses. Neither naloxone (27.5 or 55 nmol) nor mecamylamine (49.1 or 98.2 nmol) affected stimulation thresholds for inhibition of the TF reflex. Stimulation at threshold intensities for inhibition did not change the blood pressure significantly at most sites of stimulation in the NGC/NGC alpha (25/39). Intrathecal administration of atropine, phentolamine or methysergide did not affect resting blood pressure or changes associated with stimulation in most cases, although inhibition of the TF reflex by stimulation in the NGC/NGC alpha was affected consistently by these pretreatments. Similarly, glutamate (100 nmol, 0.5 microliter/1.5 min) microinjection produced a short-lasting inhibition (4.63 +/- 0.70 min, n = 19) of the TF reflex. Glutamate microinjection produced both pressor and depressor effects which were not affected by intrathecal pretreatment. Inhibition of the TF reflex by glutamate was attenuated significantly by intrathecal pretreatment with atropine, scopolamine, phentolamine and methysergide, but not naloxone or mecamylamine. These findings suggest that either a descending or local spinal cholinergic system, together with descending serotonergic and noradrenergic systems, are involved in the centrifugal inhibition of spinal nociceptive transmission from the NGC/NGC alpha.     

Sensory sciatic nerve afferent inputs to the dorsal lateral medulla in the rat

Investigations show the paratrigeminal nucleus (Pa5) as an input site for sensory information from the sciatic nerve field. Functional or physical disruption of the Pa5 alters behavioral and somatosensory responses to nociceptive hindpaw stimulation or sciatic nerve electrostimulation (SNS), both contralateral to the affected structure. The nucleus, an input site for cranial and spinal nerves, known for orofacial nociceptive sensory processing, has efferent connections to structures associated with nociception and cardiorespiratory functions. This study aimed at determining the afferent sciatic pathway to dorsal lateral medulla by means of a neuronal tract-tracer (biocytin) injected in the iliac segment of the sciatic nerve. Spinal cord samples revealed bilateral labeling in the gracile and pyramidal or cuneate tracts from survival day 2 (lumbar L1/L2) to day 8 (cervical C2/C3 segments) following biocytin application. From day 10 to day 20 medulla samples showed labeling of the contralateral Pa5 to the injection site. The ipsilateral paratrigeminal nucleus showed labeling on day 10 only. The lateral reticular nucleus (LRt) showed fluorescent labeled terminal fibers on day 12 and 14, after tracer injection to contralateral sciatic nerve. Neurotracer injection into the LRt of sciatic nerve-biocytin-treated rats produced retrograde labeled neurons soma in the Pa5 in the vicinity of biocytin labeled nerve terminals. Therefore, Pa5 may be considered one of the first sites in the brain for sensory/nociceptive inputs from the sciatic nerve. Also, the findings include Pa5 and LRt in the neural pathway of the somatosympathetic pressor response to SNS and nocifensive responses to hindpaw stimulation.     

Trigeminally induced cardiovascular reflex responses in spinalized rats

The effects on cardiovascular functions of noxious stimulation to the orofacial areas innervated by trigeminal afferent nerves were analyzed in urethane-anesthetized, spinal cord-intact rats and in rats acutely spinalized at the second cervical level. In the spinal cord-intact rats, pinching of the upper lip produced increases in both heart rate (HR) and mean arterial pressure (MAP). Both responses were considered to be due to activation of sympathetic efferent nerves to the cardiovascular organs. Both responses were attenuated but did not disappear after spinalization at the C2 level. In spinalized rats, sympathetic preganglionic neurons emerging from the thoracolumbar spinal cord could not receive any neural influences from the brain. The HR response in the spinal rats was abolished after either bilateral vagotomy or intravenous injection of a peripherally acting muscarinic cholinergic receptor antagonist, methylatropine. This suggests that the increase in HR was elicited via vagal cholinergic efferent fibers, probably by decreasing tonic activity of vagus nerves to the heart. In spinal rats, neither vagotomy nor cholinergic blockade affected the increase in MAP, but i.v. injection of the vasopressin V1 receptor antagonist, OPC-21268, abolished the response of MAP. This suggests that the response of MAP was due to peripheral vasoconstriction elicited by vasopressin secreted from the posterior pituitary lobe. The present study demonstrated that, in rats acutely spinalized at the C2 level, noxious stimulation of orofacial areas innervated by the trigeminal nerve could produce reflex increases both in HR, by decreasing cholinergic vagal nerve activity to the heart, and blood pressure, by secreting vasopressin from the pituitary gland, even though sympathetic efferent innervation to the cardiovascular organs could not be directly affected by trigeminal afferent nerve excitation.     

Tonic descending inhibition of the spinal cardio-sympathetic reflex in the cat

Electrical stimulation of the left inferior cardiac nerve elicited a two-component reflex potential (spinal and supraspinal reflexes) in the ipsilateral white ramus T3 from which recordings were made in chloralose-anaesthetised cats. Reversible interruption of all spinal pathways achieved by cooling the spinal cord at C2/C3 produced an enhancement of the spinal reflex and abolished the supraspinal reflex, the latter usually being the more prominent reflex potential prior to spinal cord block. The spinal cord block-induced increase in the amplitude of the spinal reflex was, however, less than the increase observed during stimulation of the somatic intercostal nerve T4. Recordings of the afferent volley following cardiac nerve stimulation and analysis of the stimulus-reflex response relationship in neuraxis-blocked cats indicated that the spinal reflex as determined here was activated by A delta afferent fibres. However, if stimulus strength was raised above C-fibre threshold, spinal cord block revealed in addition a late spinal reflex response. In some cases, the appearance of this late potential was accompanied by a secondary decline of the earlier spinal reflex potential, possibly indicating C-fibre-mediated afferent inhibition. Neither baroreceptor activation nor denervation had any effect on spinal reflex amplitudes. Pharmacologically, clonidine given i.v. to cats with a blocked neuraxis reduced the spinal reflex amplitudes to pre-block values, an action which could be antagonised by the subsequent administration of the alpha 2-adrenoceptor antagonist rauwolscine. When given to non-pretreated cats with intact neuraxis, however, neither rauwolscine nor its analog yohimbine were capable of inducing a persistent release from tonic inhibition. The results suggest that both purely visceral and somato-visceral reflexes are subject to tonic descending inhibition, but they do not support the hypothesis that a catecholamine is the responsible transmitter mediating this inhibition.     

Reticulospinal tracts involved in the spino-bulbo-spinal reflex in cats

Twenty-three chloralosed cats were used to examine the spinal descending pathways of the spino-bulbo-spinal (SBS) reflex.Transection of the ventrolateral funiculus in the spinal cord at the thoracic level abolished the SBS reflex of caudal spinal segments ipsilateral to the transection, but did not abolish the ascending propriospinal reflex and SBS reflex of rostral segments.Unit discharges elicited in axons of the ventrolateral funiculus at L₃ by sural nerve stimulation had the appropriate latency for mediating the SBS reflex. These axons originated in the medial bulbar reticular formation, since the responses had a consistent short latency and followed repetitive stimulation of the bulbar reticular formation (up to a rate of 300 Hz). Conduction velocities of reticulospinal axons ranged widely from 20 to 120 m/sec. There were two peaks, fast (95 m/sec) and slow (35 m/sec). The fast conducting fibers showed oligo-spikes, high amplitude and wide distribution of latency. Almost 90% of the axons with slow conduction exhibited multi-spikes, low amplitude and narrow distribution.Unitary responses of the ventral rootlet at L₇ were elicited by sural nerve stimulation and correlated with the latency of the SBS reflex. The unitary response was also evoked by train pulse stimulation of the ventrolateral funiculus in the spinal cord. Conduction velocities of descending spinal tracts ranged from 20 to 60 (mean±S.D.,35 ± 8) m/sec.We may conclude that the descending spinal pathway of the SBS reflex is the slowly conducting reticulospinal tract which originates in the medial bulbar reticular formation and passes through the ventrolateral funiculus of the spinal cord.     

Properties of ventrolateral medullary neurons that respond to muscular contraction.

Previous results from this laboratory have suggested that neurons in the ventrolateral medulla (VLM) modulate the pressor response to muscular contraction. The purpose of the present study was to determine 1) if VLM neurons with a discharge pattern related to sympathetic discharge and/or the cardiac cycle are stimulated during muscular contraction, 2) if the neurons activated by muscular contraction project to the intermediolateral columns of the spinal cord and 3) the location of glutamate immunoreactive neurons in the medulla. Single-unit responses of ventrolateral medullary neurons to hindlimb muscular contraction evoked by ventral root (L7 and S1) stimulation were recorded in one group of anesthetized cats. Computer analyses were performed to determine if the resting discharge of VLM neurons correlated temporally with sympathetic nerve discharge and/or the cardiac cycle. The discharge rate of 21 of 27 neurons which had a discharge related to sympathetic nerve activity increased during muscular contraction. Neurons in some of the experiments were tested for axonal projections to the intermediolateral nucleus (T2 or T5) of the spinal cord with antidromic activation techniques. The discharge pattern of 78% of the VLM neurons which were activated antidromically was related to the cardiac cycle or sympathetic nerve discharge. Most (92%) reticulospinal VLM neurons with cardiovascular related discharge were excited by muscular contraction. In a second set of experiments, glutamate immunoreactivity was demonstrated in neurons within an area overlapping the location of VLM neurons which were excited by muscular contraction. These findings suggest that reticulospinal neurons in the ventrolateral medulla which have a discharge pattern related to cardiovascular activity contribute to the pressor reflex evoked by muscular contraction. These neurons may utilize glutamate as a neurotransmitter.     

Evidence for a serotonergically mediated sympathoexcitatory response to stimulation of medullary raphe nuclei

The cardiovascular role of serotonin (5-HT) containing neurons in the midline medullary raphe nuclei was studied in anesthetized cats. High frequency electrical stimulation of nucleus (n.) raphe (r.) pallidus, n.r. obscurus and n.r. magnus produced both pressor and depressor responses. Single shock stimulation of pressor sites produced an excitatory evoked potential of sympathetic nervous discharge (SND) recorded from the inferior cardiac nerve. Conversely, single shock stimulation of vasodepressor sites resulted in a computer-summed inhibition of SND. The mean conduction velocity in the sympathoexcitatory medullo-spinal pathway to sympathetic preganglionic neurons was calculated to be 1.24 m/s. The 5-HT antagonists methysergide and metergoline blocked the excitation of sympathetic activity evoked from medullary raphe nuclei. In contrast, these agents failed to alter the sympathoexcitatory response to electrical stimulation of lateral medulla pressor sites or the sympathoinhibitory response elicited by raphe stimulation. The 5-HT uptake inhibitor chlorimipramine increased the duration of the sympathoexcitatory response evoked from the raphe but not from the lateral medulla. Finally, mid-collicular transection did not effect the excitation of sympathetic activity elicited by stimulation of medullary raphe nuclei. These data suggest that serotonergic neurons in the midline medullary raphe nuclei provide an excitatory input to sympathetic neurons in the spinal cord.     

Serial recording of reflexes after feline spinal cord transection

Implanted nerve cuff and muscle electrodes were used to serially record reflexes after spinal cord transection in cat. Recording of reflexes, in response to both sensory nerve and to mixed motor and sensory nerve stimulation, was accomplished through 2 months after cord section. Serial recording of afferent and efferent nerve volleys was achieved as well. Serial reflex changes that follow cord transection are described. Reflex amplitude to sensory nerve stimulation increased in two phases. The first increase was noted between 1 and 4 days after cord transection; the second increase was recorded between 2 and 4 weeks. These observations suggest that at least two neuronal mechanisms with distinct temporal courses mediate the appearance of spinal hyperreflexia. The animal model described may be useful for further study of the neuronal mechanisms which underlie the hyperreflexia of spinal cord injury.     

Role of vesical afferent nerve fibres involved in the control of internal anal sphincter motility

The neural pathways involved in the interactions between urinary bladder and internal anal sphincter (IAS) were studied in anaesthetized spinal cats. Activation of vesical afferents produced in the IAS a reflex increase in the electrical activity and a reflex inhibition of the excitatory responses evoked by stimulation of one hypogastric nerve. Both reflexes are achieved partly in the lumbar spinal cord and partly within the inferior mesenteric ganglion.     

Habituation and dehabituation of the spinal polysynaptic reflex responses: modification by naloxone and opiates and their anatomical correlates

The sustained inhibitory action of spinal endorphins could be responsible for the habituation of polysynaptic responses in the spinal cord. To test this hypothesis, acute spinalized unanesthetized cats (decerebrated and curarized) were used. Sural nerve electrical stimulation (0.2 Hz) was provided and a progressive decrease in the reflex response was found. Conversely, the field potential (lamina V) progressively increased during stimulation, reaching its maximum amplitude when ventral root response showed maximum habituation. The administration of naloxone (0.8-10.0 mg/kg) produced dehabituation or prevented habituation. The immunohistological results showed leu-enkephalin-like immunoreactive dot-like structures in close proximity to neurons of laminae VII, VIII and IX in the lumbo-sacral segment of the spinal cord. Our results suggest an involvement of opioid peptides in the habituation process.     

Midbrain central gray is involved in mediation of cholinergic inputs to the rostral ventrolateral medulla of the rat

There are cholinergic inputs responsible for pressor responses in the rostral ventrolateral medulla (RVLM) and stimulation of midbrain central gray (CG) increases arterial pressure via activation of neurons in the RVLM. In this study, we examined whether the CG was involved in mediation of the cholinergic inputs to the RVLM. Male Wistar rats were anesthetized, paralyzed, and artificially ventilated. Unilateral microinjection of L-glutamate into the CG produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine into the unilateral RVLM inhibited the pressor response to L-glutamate injected ipsilaterally into the CG, whereas microinjection of the cholinesterase inhibitor physostigmine into the RVLM enhanced it. CG stimulation also enhanced the firing rate of RVLM barosensitive neurons and the enhancement of the firing rate was inhibited by scopolamine iontophoretically applied on neurons. CG injection of L-glutamate produced a release of acetylcholine in the RVLM. Unilateral microinjection of L-glutamate into the pedunculopontine tegmental nucleus (PPT) also produced a pressor response, but the pressor response to L-glutamate was not affected by scopolamine injected ipsilaterally into the RVLM. These results provide evidence that the CG but not the PPT is involved in mediation of cholinergic inputs responsible for pressor responses in the RVLM.     

Activation of hypothalamic angiotensin receptors produces pressor responses via cholinergic inputs to the rostral ventrolateral medulla in normotensive and hypertensive rats

We have previously reported that the angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHR) and that this enhancement is involved in hypertension in SHR. In addition, acetylcholine (ACh) release is increased in the rostral ventrolateral medulla (RVLM) of SHR, which has also been shown to be involved in hypertension in SHR. In this study, we examined whether the enhanced angiotensin system in the AHA of SHR is related to the increase in cholinergic inputs to the RVLM. Electrical stimulation in the AHA produced a pressor response and an increase in firing rate of RVLM barosensitive neurons. These responses were inhibited and enhanced by RVLM application of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine, respectively. AHA stimulation also produced release of ACh in the RVLM. Microinjections of angiotensin II and carbachol into the AHA produced pressor responses. The pressor response to angiotensin II was inhibited by scopolamine microinjected into the RVLM, although this produced no effect on the response to carbachol. In SHR, although not in Wistar-Kyoto rats, microinjection of losartan into the AHA inhibited pressor responses to physostigmine. However inhibition was not observed in response to the directly acting muscarinic receptor agonist carbachol, injected into the RVLM. These findings demonstrate that angiotensin receptor activation or electrical stimulation in the AHA produce a pressor response via an increase in ACh release in the RVLM. In addition, the present study suggests that the enhanced angiotensin system in the AHA of SHR increases cholinergic inputs to the RVLM, which leads to increases in blood pressure.     

Regional depletion of central nervous system catecholamines: Effects on blood pressure and drinking behavior

The purpose of the present study was to identify which catecholamine-containing neurons (norepinephrine (NE) or dopamine (DA)) and which central nervous system (CNS) region(s) innervated by them might participate in the pressor and drinking responses produced by central drug stimulation. Forebrain NE was reduced in rats by injecting 4 micrograms of 6-hydroxydopamine (6-OHDA) into the ascending noradrenergic bundles. Spinal cord NE was depleted by intracisternal injection of 50 micrograms 6-OHDA. Depletion of forebrain DA was produced by bilateral injection of 4 micrograms 6-OHDA into the substantia nigra of desipramine-pretreated rats. Pressor responses to various doses of angiotensin II (AII), carbachol or hyperosmolar NaCl injected into the lateral ventricles (LVT); and drinking responses to LVT AII and carbachol were examined. Injection of 6-OHDA into the noradrenergic bundles reduced telencephalic and hypothalamic NE by more than 80% without significantly affecting brain DA or spinal cord NE. Intracisternal 6-OHDA depleted spinal cord NE by 80% and forebrain NE by 20-25% without reducing brain DA. Injection of 6-OHDA into the substantia nigra reduced telencephalic DA by 86% and NE by 29% without significantly affecting NE in other CNS regions. Substantia nigra 6-OHDA injected animals evidenced attenuated drinking to both LVT AII and carbachol. Pressor responses to LVT AII, carbachol and hypertonic saline were largely unaffected. Almost complete depletion of brain and/or spinal cord NE failed to alter centrally mediated drinking or pressor responses. These data indicate that the integrity of brain DA neurons is required for the behavioral but not hypertensive responses produced by central drug stimulation.     

Descending control and sensory gating of ‘fictive’ swimming and turning responses elicited in an in vitro preparation of the lamprey brainstem/spinal cord

An in vitro lamprey nervous system preparation has been developed which consists of the head and exposed brainstem attached to the isolated spinal cord (resting on the notochord). Mechanical or electrical stimulation of the snout elicits motor activity in ventral roots which underlies a turning response (head withdrawal) away from the stimulus followed by escape swimming. Direct stimulation of the sensory division of the trigeminal nerve activates these patterns, and cutting this nerve abolishes ventral root activity elicited by stimulation of the snout. These patterns of ventral root activity are correlated with muscle activity and escape movements in intact animals. Sensory input activated by passive bending of the notochord/spinal cord gates the first burst in ipsilateral ventral roots during turning motor activity, and this response can thus be considered as a position dependent ‘enhancement’ reflex. Descending pathways activated by stimulation of the snout consist of axons which project for at least 20 segments, and are not significantly dependent on propagation through local circuits in the gray matter. The in vitro brainstem/spinal cord preparation survives for several days and will permit studies of the descending systems which normally initiate two types of motor acts, swimming and turning responses.