Fictive Scratching Patterns in Brain Cortex-Ablated, Midcollicular Decerebrate, and Spinal Cats.

Background: The spinal cord's central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS. Methods: The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings. Results: In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle. Conclusion: Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.

Pharmacological evidence that dopamine inhibits the cardioaccelerator sympathetic outflow via D2-like receptors in pithed rats.

It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D1/2-like receptors or even α2-adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho-inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D2-like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 µg/kg∙min, D1-like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 µg/kg∙min) or quinpirole (100 µg/kg∙min): i) remained unaltered after saline or the antagonists SCH-23390 (D1-like, 300 µg/kg) and rauwolscine (α2-adrenoceptors, 300 µg/kg); and ii) was significantly antagonized by raclopride (D2-like, 300 µg/kg). These antagonists, at the above doses, failed to modify the sympathetically-induced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D2-like receptors but not D1-like receptors or α2-adrenoceptors.

Propagation of sinusoidal electrical waves along the spinal cord during a fictive motor task.

We present for the first time direct electrophysiological evidence of the phenomenon of traveling electrical waves produced by populations of interneurons within the spinal cord. We show that, during a fictive rhythmic motor task, scratching, an electrical field potential of spinal interneurons takes the shape of a sinuous wave, "sweeping" the lumbosacral spinal cord rostrocaudally with a mean speed of approximately 0.3 m/s. We observed that traveling waves and scratching have the same cycle duration and that duration of the flexor phase, but not of the extensor phase, is highly correlated with the cycle duration of the traveling waves. Furthermore, we found that the interneurons from the deep dorsal horn and the intermediate nucleus can generate the spinal traveling waves, even in the absence of motoneuronal activity. These findings show that the sinusoidal field potentials generated during fictive scratching could be a powerful tool to disclose the organization of central pattern generator networks.

Pharmacological profile of the clonidine-induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with alpha(2A/2C)-adrenoceptors.

BACKGROUND AND PURPOSE: Resistance blood vessels are innervated by sympathetic and primary sensory nerves, which modulate vascular tone through the release of noradrenaline and calcitonin gene-related peptide (CGRP), respectively. Moreover, electrical stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses which are mainly mediated by CGRP release. The present study has investigated the role of alpha(2)-adrenoceptors in the inhibition of these vasodepressor responses. EXPERIMENTAL APPROACH: 144 pithed male Wistar rats were pretreated with hexamethonium (2 mg kg(-1) min(-1)) followed by i.v. continuous infusions of either methoxamine (15 and 30 microg kg(-1) min(-1)) or clonidine (3, 10 and 30 microg kg(-1) min(-1)). Under these conditions, electrical stimulation (0.56-5.6 Hz; 50 V and 2 ms) of the spinal cord (T(9)-T(12)) resulted in frequency-dependent decreases in diastolic blood pressure. KEY RESULTS: The infusion of clonidine (10 microg kg(-1) min(-1)), as compared to those of methoxamine (15 or 30 microg kg(-1) min(-1)), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of alpha-CGRP (0.1-1 microg kg(-1)). This inhibition by clonidine was: (i) antagonized by 300 microg kg(-1) rauwolscine (alpha(2A/2B/2C)), 300 and 1000 microg kg(-1) BRL44408 (alpha(2A)), or 10 and 30 microg kg(-1) MK912 (alpha(2C)); and (ii) unaffected by 1 ml kg(-1) saline, 100 microg kg(-1) BRL44408, 3000 and 10,000 microg kg(-1) imiloxan (alpha(2B)) or 3 microg kg(-1) MK912. CONCLUSIONS AND IMPLICATIONS: The inhibition produced by 10 microg kg(-1) min(-1) clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional alpha(2A)/alpha(2C)-adrenoceptors.

Role of midbrain in the control of breathing in anuran amphibians.

The present study was designed to explore systematically the midbrain of unanesthetized, decerebrate anuran amphibians (bullfrogs), using chemical and electrical stimulation and midbrain transections to identify sites capable of exciting and inhibiting breathing. Ventilation was measured as fictive motor output from the mandibular branch of the trigeminal nerve and the laryngeal branch of the vagus nerve. The results of our transection studies suggest that, under resting conditions, the net effect of inputs from sites within the rostral half of the midbrain is to increase fictive breathing frequency, whereas inputs from sites within the caudal half of the midbrain have no net effect on fictive breathing frequency but appear to act on the medullary central rhythm generator to produce episodic breathing. The results of our stimulation experiments indicate that the principal sites in the midbrain that are capable of exciting or inhibiting the fictive frequency of lung ventilation, and potentially clustering breaths into episodes, appear to be those primarily involved in visual and auditory integration, motor functions, and attentional state.

Chemoreflex sympathoexcitation was not altered by the antagonism of glutamate receptors in the commissural nucleus tractus solitarii in the working heart-brainstem preparation of rats.

The changes in thoracic sympathetic nerve activity, heart rate and frequency of phrenic nerve discharge in response to chemoreflex activation before and after bilateral microinjections of glutamate receptor antagonists into the comissural nucleus tractus solitarii (cNTS) were evaluated in the working heart-brainstem preparation of rats. Microinjections of kynurenic acid (KYN, 250 mM), (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 100 mM), or KYN plus MCPG into the cNTS were performed in three different groups. These microinjections into the cNTS did not affect the increase in the thoracic sympathetic nerve activity elicited by chemoreflex activation (KYN, 54 +/- 3 versus 51 +/- 2%, n = 11; MCPG, 48 +/- 5 versus 54 +/- 5%, n = 7; and KYN plus MCPG, 57 +/- 6 versus 55 +/- 3%, n = 5). The increase in the frequency of the phrenic nerve discharge in response to chemoreflex activation was also not affected by KYN (0.28 +/- 0.02 versus 0.30 +/- 0.04 Hz), MCPG (0.27 +/- 0.03 versus 0.27 +/- 0.04 Hz), or KYN plus MCPG (0.30 +/- 0.04 versus 0.20 +/- 0.03 Hz). The bradycardic response to chemoreflex activation was significantly reduced after microinjection of KYN at 2 (-220 +/- 16 versus -50 +/- 6 beats min(-1)) and 10 min (-220 +/- 16 versus -65 +/- 9 beats min(-1)) and after microinjection of KYN plus MCPG into the NTS it was abolished at 2 (-192 +/- 14 versus -2 +/- 1 beats min(-1)) and 10 min (-192 +/- 14 versus -4 +/- 2 beats min(-1)). These data support the hypothesis that the neurotransmission of the sympathoexcitatory and respiratory components of the chemoreflex in the cNTS involves neurotransmitters other than L-glutamate and also the concept that the parasympathetic component of this reflex is mediated by L-glutamate.

Gamma->alpha linkage and persistent firing of Ia fibers by pudendal nerve stimulation in the decerebrate cat.

The sensory pudendal nerve (SPN) was stimulated in decerebrate female cats. Spikes of single Ia muscle spindle afferents from the medial gastrocnemius (MG) muscle were recorded in dorsal root filaments. Electroneurography (ENG) was recorded in a cut nerve filament to the MG muscle; MG electromyography (EMG) was also recorded. Single shock to SPN induced discharges of small ENG spikes (SS) with similar amplitude to that of gamma spikes elicited by ventral root stimulation. Thus SS were identified as gamma spikes. The latency of the gamma discharge was approximately 15 ms. As expected, the onset of the gamma discharge preceded a discharge of Ia spikes; the time difference between both discharges was approximately 5 ms. After the initial bursts, the Ia and the gamma activities paused during 20-30 ms but later increased again to last approximately 1 s. After the shock, the EMG activity was depressed during approximately 50 ms; later, motor-unit spikes may show transient activation. Thus the onset of the gamma activation preceded the activation of motor units (gamma-->alpha link). Trains of shocks (1 or 100 Hz) to SPN induced a sustained increase in the frequency of gamma spikes, Ia spikes, and motor units that outlasted the train by 20-120 s. The sustained firing of Ia fibers might trigger or help to trigger and maintain the response of alpha-motoneurons.

Sympathetic innervation of mammary glands mediates suckling-induced reflex inhibition of milk yield in rats.

Previous work has shown that physiologic activation of the sympathetic system may inhibit milk yield (ME) in rats. Thus, adrenal catecholamines (CAs) are released by suckling, but it is not known whether such inhibition results also from reflex activation by the same stimulus of neural sympathetics upon the mammary gland. The present experiments were designed to determine whether suckling inhibits ME induced by oxytocin (OT) in the urethane-anesthetized lactating rat, and whether such inhibition results from adrenal and/or neurally released CAs. Rats were isolated (6 h) from their pups and then anesthetized. OT (0.8 mU every 2 min) was administered intravenously to the mothers during suckling. Rats were either chronically implanted with cannulae into the lateral cerebral ventricles (intracerebroventricularly), bilaterally adrenalectomized (ADX), hypophysectomized (HX), spinal cord transected (SCT: T3-T4), or had the nipple area (NA) locally anesthetized before suckling. MEs were low in control, sham, ADX and HX rats, but not in rats given the beta-adrenergic blocker propranolol (PROP; intravenously or intracerebroventricularly injected), nor in SCT, NA or PROP-HX rats. As revealed by ductal resistance measurements as an indicator of ductal tone, suckling-induced inhibition of ME was due to ductal constriction within the mammary glands. These effects of suckling, however, could be prevented by prior activation of ductal mechanoreceptors. Together, these results indicate that suckling inhibits ME through the reflex activation of neurally mediated central beta-adrenergic mechanisms, and that these effects, in turn, can be regulated by ductal mechanoreceptor activation.

Exhaustion of the coital reflex in spinal male rats is reversed by the serotonergic agonist 8-OH-DPAT.

Previous studies from our laboratory have shown that the genital motor pattern associated to the coital reflex in spinal male rats becomes exhausted when repeatedly evoked. Exhaustion of the genital motor pattern could be related to the sexual exhaustion phenomenon observed in copulating male rats. The present study was aimed to describe the features of coital reflex exhaustion and to determine if the 5-HT1A agonist 8-OH-DPAT was able to reverse exhaustion of this ejaculatory-like response. Additionally, the effect of pre-treatment with the 5-HT1A antagonist WAY 100635 on the 8-OH-DPAT induced motor response was evaluated. Results revealed that development of coital reflex exhaustion initiated with a progressive increase in the latency of response and was characterised by a change in the properties of the motor pattern itself. Once exhausted, i.v. administration of 8-OH-DPAT provoked the immediate expression of a potent motor pattern similar to the coital reflex, but in the absence of urethral stimulation. Injection of WAY 100635 induced, per se, expression of the coital reflex after exhaustion. Notwithstanding, pre-treatment with WAY 100635 was able to block the 8-OH-DPAT-induced motor response implying that its effect was exerted upon 5-HT1A receptors. Data suggest that the sexual exhaustion phenomenon might possess a spinal component.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats. Evidence for a somatotopic organization.

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61% of the times and an increase of blood pressure and heart rate in approximately 80% of the stimulations. Stimulation of a hindlimb provoked an increase of blood flow in the same limb in about 80% of the stimulations, due to active vasodilation. Contralateral stimulation provoked a smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs. The vasodilation was not due to activation of sympathetic cholinergic vasodilator neurons inasmuch as the blood flow responses were not affected by cholinergic blockade with atropine. In spinal animals, stimulation of any limb provoked small increases of blood pressure, extremely low degrees of tachycardia and an increase of hindlimb blood flow, with active vasodilation. Neuromuscular paralysis, however, abolished the adjustments of blood flow in the hindlimbs, indicating that metabolites and/or sensory information caused by muscle contraction induced them. In intact cats anesthetized with sodium pentobarbiturate, blood pressure and heart rate increased under noxious stimulation, although less than in the decerebrate animals. Nearly 40% of the stimulations provoked hypotension rather than hypertension. Blood flow increased due to stimulation of any limb but, as in the decerebrate preparation, there was active vasodilation in the ipsilateral hindlimb and vasoconstriction in the contralateral one.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats: evidence for a somatotopic organization

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61 percent of the times and an increase of blood pressure and heart rate in approximately 80 percent of the stimulations. Stimulations of a hindlimb provoked an increase of blood flow in the same limb in about 80 percent of the stimulations, due to active vasodilation. Contralateral stimulation provoked as smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs...

[The alpha-antiadrenergic properties of spiroxatrine, a ligand of serotonergic 5-HT1A receptors]. / Propiedades antiadrenérgicas alfa de la espiroxatrina, un ligando de los receptores serotonérgicos 5-HT1A.

The 5-HT1A ligand, spiroxatrine, displays very low affinity for alpha 1-adrenergic binding sites and a relatively high affinity for alpha 2-adrenergic binding sites. Nonetheless, recent functional studies indicate that spiroxatrine is a potent antagonist of the alpha 1-adrenoceptor mediating contraction in the rat isolated aorta. On the basis of the widely studied heterogeneous interaction of drugs with alpha-adrenoceptors in several experimental models, the present study was designed to analyze the alpha-adrenoceptor antagonist properties of spiroxatrine in the pithed rat. Animals were prepared for recording of arterial blood pressure and intravenous (i.v.) administration of drugs. Norepinephrine and the alpha 1- and alpha 2- adrenoceptor agonists methoxamine and clonidine, respectively, elicited pressor responses in a dose-related fashion. Spiroxatrine (1 mg/kg, i.v.) produced a moderate--but significant--rightward displacement of the dose-response curves to all agonists. The present data lead us to suggest that, though spiroxatrine exhibits alpha 1- and alpha 2-adrenoceptor antagonist properties in the pithed rat, its potency does not seem to correlate with that found in rat aorta. The potential involvement of alpha 1-adrenoceptor subtypes is discussed.

Decerebrate rigidity with preserved cognition and gait: a possible role of anoxic-ischemic brain damage.

A case of stable decerebrate posture in the upper limbs following sudden loss of consciousness and prolonged coma is described. The patient recovered most of her cognitive functions and gait, without clinical, neurophysiological or neuroradiological evidence of brainstem lesion. MRI shows borderzone infarcts. It is suggested that anoxic-ischemic cortical damage, affecting specially corticoreticular neurons, could explain the development of decerebrate rigidity in patients without apparent brainstem lesion.

Massed amygdaloid kindling in encéphale isolé cats: its facilitation by naloxone.

The effect of repetitive administration of naloxone on the development of massed amygdaloid kindling in 'encéphale isolé' cats was studied. Electrical amygdaloid kindling was carried out with a 15 min inter-stimulus interval (ISI) in a control situation with intravenous (i.v.) naloxone administration (2, 4, and 8 mg/kg), 5 min prior to amygdaloid stimulation. It was found that it was possible to complete the amygdaloid kindling process in the encéphale isolé preparation reaching generalized electrographic tonic-clonic self-sustained seizures. The enhancement of the duration, frequency, and propagation of the after-discharge (AD) was accentuated by naloxone which also induced a progressive amplitude increment of the first potential evoked by the onset of the tetanus. The number of trials needed to achieve seizure generalization was reduced in dose-dependent manner by naloxone. The ability of naloxone to accelerate the development of amygdaloid kindling may be related to an inhibitory role of opioid peptides in this process.

Cardiovascular regulation in the acute decerebrate rat.

Male Wistar rats were decerebrated at precollicular level, by aspiration, under ether anaesthesia. The experiments employed rats instrumented for chronic electrocardiogram (ECG) recordings or mean blood pressure (MBP) and heart rate (HR) determination. Immediately after surgery, decerebrate (D) and sham operated (SO) animals presented a small and similar increase in their HR. Three and a half hours after surgery, SO group presented a normal HR, whilst D animals continued to show an increase in their HR up to 4.5 h, when it stabilized. Twenty four hours after surgery both groups presented similar MBP (D:110 +/- 6; SO:108 +/- 1 mmHg) but displayed marked differences on their HR (D:550 +/- 11; SO:335 +/- 5 beats/min). The blockade of parasympathetic tonus induced significant increases in the HR of both groups, without major changes in their MBP. Beta-adrenergic blockade reduced HR of both groups, bringing HR of D almost to control level. Simultaneously there was a reduction in MBP of D but not of SO animals. When parasympathetic blockade was superimposed to beta-adrenergic blockade, there was a significant increase in HR of SO, but not of D or in MBP of both groups. Thus we conclude that the decerebrate rat presents normal MBP with simultaneous tachycardia mainly caused by increased sympathetic outflow to the heart.

Cardiovascular regulation in the acute decerebrate rat

Male Wistar rats were decerebrated at precollicular level, by aspiration under ether anaesthesia. The experiments employed rats instrumented for chronic electrocardiogram (ECG) recordings or mean blood pressure (MBP) and heart rate (Hr) determination. Immediately after surgery, decerebrate (D) and sham operated (SO) animals presented a small and ismilar increase in their HR. Three and a half hours after surgery, SO group presented a normal HR, whilst D animals continued to show an increas ein their HR up to 4.5 h, when it stabilized. Twenty four hours after surgery both groups presented similar MBP (D:110ñ6; SO:108ñ11; SO:335ñ5 beats/min). The blockade of parasympathetic tonus induced significant increases in the HR of both groups, withou major changes in their MBP. Beta-adrenergic blockade reduced HR of both groups, bringin HR of D almost to control level. Simultaneously there was a reduction in MBP of D but not of SO animals. When parasympathetic blockade was superimposed to beta-adrenergic blockade, there was a significant increase in HR of SO, but not of D or in MBP of both groups. Thus we conclude that the decerebrate rat presents normal MBP with simultaneous tachycardia mainly caused by increased sympathetic outflow to the heart (AU)

Cardiovascular regulation in the acute decerebrate rat

Male Wistar rats were decerebrated at precollicular level, by aspiration under ether anaesthesia. The experiments employed rats instrumented for chronic electrocardiogram (ECG) recordings or mean blood pressure (MBP) and heart rate (Hr) determination. Immediately after surgery, decerebrate (D) and sham operated (SO) animals presented a small and ismilar increase in their HR. Three and a half hours after surgery, SO group presented a normal HR, whilst D animals continued to show an increas ein their HR up to 4.5 h, when it stabilized. Twenty four hours after surgery both groups presented similar MBP (D:110ñ6; SO:108ñ11; SO:335ñ5 beats/min). The blockade of parasympathetic tonus induced significant increases in the HR of both groups, withou major changes in their MBP. Beta-adrenergic blockade reduced HR of both groups, bringin HR of D almost to control level. Simultaneously there was a reduction in MBP of D but not of SO animals. When parasympathetic blockade was superimposed to beta-adrenergic blockade, there was a significant increase in HR of SO, but not of D or in MBP of both groups. Thus we conclude that the decerebrate rat presents normal MBP with simultaneous tachycardia mainly caused by increased sympathetic outflow to the heart

[Relationship of decerebrate rigidity maintenance with muscular contraction permanence after spinal cord section in dogs]. / Relações do tempo de manutenção da rigidez de descerebração com permanência de contratura muscular após transsecção da medula espinhal, em cães

The mammalian spinal cord seems to be capable of information retation in simmilar fashion to the cerebral cortex memory storation. The intercollicular transection otherwise, relieving bulbar and mesencephalic areas from cerebral and cerebelar influences produces tetanic contraction on antigravidity muscles due to somatory with stimuli originated from muscle spindle. This phenomena is very suitable to memory retention studies since myotatic reflex is monossinaptic, occurs in this case, on a simple nervous structure (the spinal cord) and can be easily identified and quantitified, through muscular responses. In the present work, decerebrate rigidity effects upon spinal cord before and after spinal section, was studied. Physiological parameters were recorded in order to maintain the experimental condition of the dogs, as close as possible to normal, Our results showed that thirty and forty-five minutes in time difference of decerebrate rigidity influence on spinal motoneurons has little effects in tetany persistance after spinal section. However, ninety minutes period of time between the two transections produces considerable increase in rigidity permanence after spinal cord section. The relationship of our results with differents types of memory and the basic mechanism involved in the response is unknown and will be the subject of future investigations.