Microinjection Of Kainic Acid Research Articles

Spontaneous secondarily generalized convulsions induced by a single microinjection of kainic acid in cats

Spontaneous secondarily generalized convulsions induced by a single microinjection of kainic acid in cats

Suppression of self-stimulation of the medial prefrontal cortex after local micro-injection of kainic acid in the rat

The question of whether neurons versus fibers of passage in the medial prefrontal cortex (MPC) are essential in maintaining self-stimulation of this same area of the brain was examined. Rats were prepared with electrode-guide cannulae implanted stereotaxically to rest within MPC. A micro-injection of (KA), 10 nmol/1.0 μl, into the right MPC produced a clear degeneration of neuronal cell bodies characterized by picnocytosis and glial invasion of the tissue surrounding the tip of the electrode. These histopathological changes were correlated with a permanent abolition of self-stimulation of the right MPC. In contrast, self-stimulation of the contralateral side of the MPC, micro-injected with 0.9% NaCl vehicle as a control, was unaffected. These results suggest that neurons of the MPC are part of the neural substrate underlying self-stimulation behavior in this cortical area of the rat.

Brain stem area with C1 epinephrine neurons mediates baroreflex vasodepressor responses.

In anesthetized, paralyzed rats, bilateral electrolytic lesions of rostral ventrolateral medulla (RVL) containing epinephrine neurons of the C1 group 1) abolished the reflex hypotension and bradycardia elicited by electrical stimulation of the left vagus nerve or stretch of the left carotid sinus and 2) reduced arterial pressure (AP) and heart rate (HR) to values comparable to spinal cord transection. Combined lesions of the right nucleus tractus solitarii (NTS) and left or right C1 area did not alter AP. However, lesions of right NTS combined with lesions or microinjection of kainic acid into the left, but not right, C1 area abolished vasodepressor reflexes. Vasodepressor reflexes were unchanged by midcollicular decerebration, bilateral lesions of the parabrachial complex of the pons, or (after right NTS lesions) by lesions of the raphe or other reticular areas of the left half of the medulla. We conclude that neurons of the RVL, possibly belonging to the C1 epinephrine group, mediate vasodepressor responses from arterial baro- and other cardiopulmonary receptors, the pathway may be via a direct NTS-RVL projection, neurons in the C1 area of RVL are necessary for maintaining resting levels of arterial pressure.

Caudal ventrolateral medulla. A region responsible for the mediation of vasopressin-induced pressor responses.

We localized glutamate-sensitive sites in the ventrolateral medulla of the rat with the spinal cord cut at C. When unilaterally injected into a circumscribed region of the caudal ventrolateral medulla, L-glutamate (30-300 ng) elicited a dose-dependent increase in arterial pressure. The pressor response was accounted for by an increased release of vasopressin because it was abolished by the intravenous injection of a vasopressin antagonist. Bilateral microinjections of kainic acid (50 ng) into the ventrolateral glutamate-sensitive area markedly reduced a vasopressin-induced pressor response to kainic acid (30 ng), injected bilaterally into the nucleus tractus solitarii. It is concluded that the glutamate-sensitive neurons in the caudal ventrolateral medulla are involved in mediation of the vasopressin-induced pressor response arising from the nucleus tractus solitarii.

An animal model for neuron-specific spinal cord lesions by the microinjection of N-methylaspartate, kainic acid, and quisqualic acid.

It has been shown that N-methylaspartate (NMA), kainic acid (KA), and quisqualic acid (QA) can produce preferential neuronal damage in various parts of the striatum, hippocampus, and thalamus with relative sparing of axons in transit. Thus far, the evidence that axons in transit escape destruction has been based largely on histological observations. To test the functional integrity of axons in passage, we made unilateral lesions with these agents in the cervical spinal cord of rats and compared the subsequent functional deficits with those seen after spinal cord hemisections. Observations were made in 14 rats. In each case, a laminectomy at the C6-C7 level was performed under general anesthesia. Animals receiving microinjections of KA, QA, or NMA showed motor and sensory deficits only in the ipsilateral forepaw and remained able to use the hindpaws normally. By contrast, animals undergoing spinal cord hemisection developed obvious motor deficits in the ipsilateral hindpaw in addition to the deficits in the forepaw. Histological observations of the spinal cords confirmed an extensive gray matter destruction with relative preservation of the long tracts in animals injected with KA, QA, and NMA. In addition, it was noted that spinal cord neurons appear relatively less sensitive to KA and more sensitive to QA than neurons in the thalamus, striatum, or hippocampus. The possible application of these findings for the production of dorsal root entry zone lesions will be discussed.

Electrographic effects of kainic acid microinjections in limbic structures of developing rats

Electrographic effects of kainic acid microinjections in limbic structures of developing rats

The auditory neurophonic: Basic properties

In anesthetized cats an AC signal or neurophonic can he recorded from the auditory nerve and from the scalp when the cochlea is stimulated with low frequency tones. This study examines some of the basic properties of the auditory neurophonics. The auditorynerve signal, termed the auditory nerve neurophonic (ANN), was differentially recorded with a pair of plalinum-iridium ball electrodes placed on either side of the auditory nerve as it exits the internal meatus. The signal recorded from the scalp, termed the frequency following response (FFR), was recorded with silver wire. For purposes of comparison the round window-recorded cochlear microphonic was also examined under identical stimulus conditions. Several measures of the response to acoustic stimulation were taken for each recording configuration. Among these were total response amplitude as a function of stimulus level, spectral component amplitude and phase as a function of stimulus level, fundamental component amplitude as a function of stimulus frequency, response amplitude as a function of time after stimulus onset, response amplitude as a function of forward masker intensity. By all these measures the neurophonic responses are signals that are distinct from the CM and share many of the properties of single units in the auditory nerve. In addition, micro-injections of kainic acid into the cochlear nucleus leave these responses largely unaffected, while tetrodotoxin injections into the cochlea greatly diminish both neurophonic responses, while leaving the CM largely intact. From these results, we conclude that at stimulus levels below 90 dB SPL the ANN is almost entirely neural in origin, while the FFR is certainly largely neural, that is, that both responses are quite distinct from the CM. We also conclude that they represent a spatial summation of neural activity in the auditory nerve, probably arising from the phase-locked response of single units to low frequency stimuli. In addition to demonstrating that the neurophonics are neural responses, we have begun the process of relating their properties to the distributed phase-locked activity in the auditory nerve. auditory nerve, frequency following response, eochlear microphonic

Location of the area postrema pressor pathway in the dog brain stem.

Electrical stimulation of the dog's area postrema (AP) induces a response that mimics the pressor response produced by intravertebral infusion of low-dose angiotensin II, which causes an increase in mean arterial pressure associated with transient tachycardia and increased peripheral resistance. The present study investigated in morphine-chloralose anesthetized dogs whether: 1) the characteristics of the AP pressor response are influenced by the presence of carotid sinus afferents; 2) structures rostral to the medulla influence the AP pressor response; and 3) the pressor pathway is initiated by neurons within the AP. Since bilateral cervical sinovagal denervation, which potentiated the phenylephrine pressor response, did not affect the pressor response to AP stimulation, the data provide evidence for an inhibitory influence exerted upon the central baroreflex mechanism by the AP pressor mechanism. The unaltered AP pressor response after midcollicular transection suggests that the efferent pathway is contained within the brain stem caudal to the pons. Finally, the elimination of the pressor response following kainic acid microinjection into the AP provides evidence that the AP pressor mechanism is initiated by neurons within the AP, rather than by fibers of passage from other pressor centers. These results suggest that the AP produces its facilitation of central sympathetic vasomotor outflow via a pathway contained within the medulla.

Suppression of arterial pressure, heart rate and cardiac contractility following microinjection of kainic acid into the nucleus ambiguus of the rat

In pentobarbital anesthetized rats, unilateral microinjection (500 ng) of the selective perikaryal excitotoxin, kainic acid, into the nucleus ambiguus promoted a significant suppression of arterial pressure, heart rate and cardiac contractility. The degree of such cardiovascular depression followed the order of heart contractility reduction (50.7%) greater than hypotension (28.9%) greater than bradycardia (20.8%) at the end of a 60-min postinjection period. We concluded that the nucleus ambiguus may exert its control on cardiac activities by both negative chronotropic and inotropic effects on the heart.

Phasic paradoxical sleep precipitates focal motor and limbic seizures

The facilitatory or inhibitory effect of paradoxical sleep (PxS) was investigated in two models of focal epilepsy: focal motor seizures induced by alumina cream in the frontal cortex and limbic seizures produced by intra-amygdaloid kainic acid microinjections in cats. We found that phasic episodes of PxS could trigger both types of seizures. Interictal spikes were generally blocked during PxS. We conclude that PxS exerts facilitatory or inhibitory effects depending on the particular event under analysis and the degree of epileptogenicity. The capacity of phasic PxS to precipitate focal ictal discharges may depend on pontolimbic excitatory influences.

The effect of kainic acid microinjections into nucleus raphe dorsalis on brain excitability level in cat

The effect of kainic acid microinjections into nucleus raphe dorsalis on brain excitability level in cat

Vasopressin-Induced Pressor Responses Following Microinjection of Kainic Acid into the Nucleus Tractus Solitarii of the Rat

Vasopressin-Induced Pressor Responses Following Microinjection of Kainic Acid into the Nucleus Tractus Solitarii of the Rat

Intracortical and intrahippocampal injections of kainic acid in developing rats: An electrographic study

Electrographic patterns induced by neocortical and hippocampal microinjections of kainic acid (KA) have been studied in curarized 4–30-day-old rats. In younger (4–6-day-old) animals, both hippocampal and neocortical KA application induced, with a long delay, the appearance of sequences of slow spikes, simultaneously occurring in the cortex and hippocampus. The same pattern was observed in about 60% of animals 7–9 days old. In the remaining 40% of the rats of this age, epileptic abnormalities, initially localized in the neocortical or hippocampal injection site were obtained. The latter pattern always appeared in 10–14-day-old rats. In some of these status epilepticus was also reached. In older (15–30 days) animals, the hippocampal injection caused the appearance of hippocampal seizures, always evolving into status epilepticus. In neocortically injected animals, cortical bursts of polyspikes appeared, with or without hippocampal involvement. After 40–60 min, typical hippocampal seizures occurred, later leading to status epilepticus. The simultaneous hippocampal and neocortical response observed in younger rats is attributed to a massive activation of the immature brain structures. The focal response seems to be correlated with a maturational process of glutamate and/or kainate receptors at both hippocampal and neocortical levels. This process is completed during the third week, when a typical selective activation of the limbic structures is obtained.

Evidence for a bulbospinal serotonergic pressor pathway in the rat brain

The cardiovascular role of spinal serotonin (5-HT) neurones descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal animals and in animals with selective chemical ablation of 5-HT nerves. These laterally placed 5-HT nerves fall within the B1 and B3 groups in the medulla and were identified using immunohistochemistry. 5,7-Dihydroxytryptamine (5,7-DHT) was injected into the lateral cerebral ventricle (i.c.v.) to produce a generalized destruction of central 5-HT pathways, with preliminary intraperitoneal administration of desipramine to prevent depletion of noradrenaline stores. In other experiments, 5,7-DHT was injected directly into the cervical spinal cord, after preliminary treatment with desipramine, to produce selective destruction of spinal 5-HT nerves, confirmed both biochemically and immunohistochemically. Electrical stimulation near the lateral 5-HT cells in the B1 and B3 cell groups elicited pressor responses in control (vehicle-injected) rats; the increase in mean arterial pressure was proportional to the intensity and to the frequency of stimulation. Microinjections of kainic acid or l-glutamate at the same sites also produced an increase in mean arterial pressure. Selective destruction of 5-HT nerves, whether produced by i.c.v. or intra-spinal administration of 5,7-DHT, reduced the magnitude of the pressor response to electrical stimulation by over 50%. These experiments suggest the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the intermediolateral cell column serves to elevate arterial pressure and maintain vasomotor tone.

Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum

Nigrostriatal dopaminergic neurons are thought to be critically important for somato-sensorimotor behavior. Following unilateral irreversible elimination of these neurons, an animal shows an ipsiversive postural bias and permanently fails to orient its head toward tactile stimuli placed on the contralateral side of the body. In response to apomorphine, a dopamine agonist, these rats display contraversive circling. This effect is thought to reflect denervation-induced proliferation of dopamine receptors in the ipsilateral striatum. We have developed a sensitive procedure that measures sensorimotor function independent of postural and circling biases. We record the latencies to remove small pieces of adhesive stimuli placed onto the snout or radial surface of the forelimbs. The stimuli are placed symmetrically and simultaneously, which is analogous to tactile-extinction procedures used clinically. In the first study we found that rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal pathway showed a contralateral sensorimotor bias in response to doses of apomorphine below those necessary to produce contraversive circling. In a second study, unilateral striatal microinjections of kainic acid (KA) were used to destroy the neurons on which the postsynaptic dopaminergic receptors of the nigrostriatal system are contained. Compared to 6-OHDA, KA produced unexpected results in standard orientation tests. None of the KA-treated rats showed contralateral neglect, and some even showed ipsilateral deficits. However, the standard orientation tests are confounded by postural asymmetries, which were irregular in the KA-treated group. Using again the posture-independent sensorimotor procedure, we found that all KA-treated rats, like the 6-OHDA-treated rats, uniformly displayed ipsilateral sensorimotor biases. Sensorimotor function relating to inter-striatal asymmetries may be more specifically assessed with the bilateral-adhesive tests.

Kainic acid lesioning of alkaloid-sensitive brain sites and ethanol ingestion in the rat

A control alcohol (ethanol) preference test was first goven to adult male Sprague-Dawleyrats which were provided water together with alcohol increased in concentrations from 3 to 30% over 8 days. Then each rat was anesthetized and a two-stage, bilateral lesion was made stereotaxically by microinjection of kainic acid in a dose of 0.5 μg into the hippocampus, cingulate gyrus or periaqueductal gray. Specifically selected sites were based on earlier experiments in which the application of a tetrahydrisoquinoline alkaloid was found to induce an increase in alcohol drinking. Two weeks later, the 8-day test of self-selection for alcohol was repeated. Although neurological signs of kainic acid lesions were apparent, no significant differences in alcohol drinking in terms of proportion or g/kg intake occured after either the first or second stage of the lesion. These results show that local destruction of an alkaloid-sensitive site does not appear to be responsible for induction of aberrant dinking of alcohol.

Visual pattern discrimination through interactions of neural networks: a combined electrical brain stimulation, brain lesion, and extracellular recording study inSalamandra salamandra

In freely movingSalamandra salamandra various brain sites (n = 33) were stimulated monopolarly via chronically implanted electrodes. Stimulation of the optic tectum mainly elicited prey-catching behavior (mean lower current threshold Ilt = 9 μA) and sometimes predator-avoidance behavior (Ilt = 28 μA). Stimulation of the caudal dorsal (Ilt = 27 μA) or rostral dorsal thalamus (Ilt = 26 μA) exclusively released avoidance movements, such as ipsiversive turning, running, or moving backward. Telencephalic stimulation (Ilt = 66 μA) activated backward-creeping, trunk-raising, or jaw-opening/closing. Brain lesions were produced inn = 64 fire salamanders either by anodal DC current, radiofrequency current, Kainic acid micro-injections, or micro-knife cuts. After ablation of the optic tectum, both visually guided prey-catching and predator-avoidance behaviors failed to occur. Unilateral lesions in the following prosencephalic brain areas caused a strong deficit of configurational prey-selection (‘disinhibition of prey-catching behavior’) and a failure of visual predator-avoidance behavior in response to stimuli moving in certain areas of the visual field: (i) caudal dorsal thalamus (entire contralateral visual field), (ii) rostral dorsal thalamus (frontal visual field of both eyes), and (iii) medial pallium (entire visual field of both eyes). Lesions in the lateral pallium led to a decrease in the threshold of visually guided predator-avoidance behavior. Action potentials were extracellularly recorded from single tectal T5 neurons in intact animals and following various prosencephalic lesions (i), (ii), or (iii). In all of then = 14 investigated neurons the same alteration of response properties was obtained, corresponding to the change in behavior. Recordings from a single prey-selective class T5(1) neuron pre and post DC coagulation in the ipsilateral caudal dorsal thalamus produced: an increase in the diameter of the excitatory receptive field (ERF) from ≈30 ° to ≈50 ° and a strong deficit in selectivity with regard to moving configurational visual stimuli.

Limbic status epilepticus: behaviour and sleep alterations after intra-amygdaloid kainic acid microinjections in Papio papio baboons

Limbic status epilepticus was produced with single microinjections of kainic acid in the amygdala of baboons ( Papio papio). Long-term studies of the behavioral, electrographic and sleep alterations were performed. During status epilepticus the animals did not display aggressive behaviour. Feeding behaviour was diminished. Sleep was also deeply disturbed. Wakefulness was greatly increased, light slow wave sleep was diminished and deep slow wave sleep and paradoxical sleep were abolished. Sleep alterations persisted throughout the duration of status epilepticus (48–72 h). A modulation of paroxysmal discharges was observed depending on the degree of epileptogenicity of the limbic focus. Increased wakefulness cannot be attributed to convulsions since limbic status epilepticus in baboons is not accompanied by positive motor signs. It is proposed that increased wakefulness, of a particular type as revealed by the alterations of different accompanying behaviours, during this type of status epilepticus, depends on an internal arousing mechanism.

Positron emission tomography in a case of experimental focal epilepsy in the baboon

Repetitive limbic status epilepticus was produced in one baboon by intraamygdaloid microinjection of kainic acid. Brain metabolims was analysed by positron emission tomography (PET) after intravenous administration of 18fluorodexyglucose ( 18FDG). In a control examination the distribution of 18FDG was symmetric in homologous parts of the brain. In contrast, during the epileptic state a restricted zone, the fronto-temporal region, showed increased 18FDG incorporation. This region corresponded to the side of kainic acid injection and to the limbic epileptogenic focus as demonstrated by EEG recording. The use of the non-invasive PET technique is suggested as an adjunct to classical EEG and clinical observations for the location of an epileptic focus generating a status epilepticus.

Correlation between rotational behaviors and neurochemical changes associated with damage of rat striatum: Analysis using unilateral microinjection of kainic acid

The correlation between rotational behaviors and neurochemical changes associated with the striatal damage induced by an unilateral microinjection of kainic acid were investigated. Shortly after the unilateral striatal injection of kainic acid, rats exhibited contralateral rotational behaviors, and these changes were antagonized by the simultaneous striatal injection of haloperidol. On the other hand, systemic injection of methamphetamine to animals having the lesion on nigro-striatal dopaminergic neurons exhibited ipsilateral turnings. In addition, it was found that the release of [ 14C]dopamine from striatal slices was increased by the in vitro addition of kainic acid. Following 2 days after the striatal injection of kainic acid and thereafter, the rats exhibited ipsilateral rotational behaviors and microinjection of muscimol into the ipsilateral substantia nigra of these animals altered turning movements to a contralateral type. Simultaneous nigral injection of bicuculline antagonized to the muscimol-induced contralateral turnings. These results suggest that the increase of dopamine release from dopaminergic neurons in the striatum may be involved in the occurrence of contralateral turning behaviors observed shortly after the striatal kainic acid treatment. The present results also suggest that changes in the functional states of striatonigral GABA-ergic neurons may play an important role in the occurrence of ipsilateral rotational movements at a late stage following the striatal injection of this agent.