P77PMC大鼠听源性惊厥神经回路──核团损毁研究

采用立体定位直流电损毁法,分别损毁双侧下丘、脑桥吻侧网状核、内侧膝状体、黑质,观察核团损毁对大鼠听源性惊厥行为的影响,以寻找与P77PMC大鼠听源性惊厥有关的神经核团。结果表明：双侧下丘损毁后能完全阻断强直阵挛性惊厥,脑桥吻侧网状核损毁能明显减少惊厥发生（P＜0．05）,而双侧内侧膝状体及黑质损毁对惊厥无明显影响（P＜0．05）。提示下丘是P77PMC大鼠听源性惊厥的关键核团,而脑桥吻侧网状核可能参与了惊厥回路,内侧膝状体可能并未参与惊厥回路,黑质在此惊厥中的作用尚不明确。     

Disconnection of the amygdala central nucleus and substantia innominata/nucleus basalis disrupts increments in conditioned stimulus processing in rats

Rats with a neurotoxic lesion of the amygdala central nucleus (CN) in one hemisphere and a 192 immunoglobulin G (192IgG)-saporin lesion of cholinergic neurons in the contralateral substantia innominata/nucleus basalis (SI/nBM) failed to show the enhanced attentional processing of a conditioned stimulus (CS) observed in sham-operated rats when that CS's predictive value was altered. Performance of these asymmetrically lesioned rats was poorer than that of rats with a unilateral lesion of either structure or with a symmetrical lesion of both structures in the same hemisphere. These results implicate connections between the CN and SI/nBM in the incremental attentional processing of CSs, extending previous research that has shown similar effects of bilateral lesions of either the CN or the SI/nBM.     

Neophobia, conditioned taste aversion and EEG arousal after globus pallidus lesion

Rats with unilateral or bilateral electrolytic lesions in the globus pallidus (GP) became aphagic and adipsic. Aphagia and adipsia lasted 2-3 days in rats with unilateral lesion, but were more persistent in animals with bilateral lesions. EEG arousal induced by nociceptive stimuli applied to the side of the body contralateral to the unilateral pallidal lesion was of shorter duration than that induced by ipsilateral stimulation; no difference was found between rats injured in left or right (GP). Total exploratory activity of rats with symmetrical or asymmetrical lesions, exposed to a novel environment for ten min, was not different from that of the control group, but the exploratory activity measured in a 60 sec block showed trends in the two injured groups being different than those in the controls. Rats with unilateral right or bilateral lesions showed a lower level of neophobia for saccharin than controls. Acquisition of conditioned taste aversion was similar in lesioned rats and controls, but extinction of the conditioned taste aversion was slower in the intact than in the injured animals.     

Evidence for a longitudinal pathway in rat hypothalamus that controls FFA mobilization

In initial exploratory experiments, bilateral, symmetrical, relatively large electrolytic lesions were produced, injuring anterior, middle, and posterior hypothalamus but respecting the midlateral region. Only lesions in the preoptic-anterior hypothalamic region and in the posterior hypothalamus were effective in blocking free fatty acid (FFA) mobilization induced by intravenous 2-deoxyglucose. Lesions in the ventromedial hypothalamus were ineffective. In subsequent experiments, suppression of plasma FFA response to the drug was observed in rats with small, globular (0.5-1.0 mm diam), bilateral lesions either in the preoptic (PO) or in the lateral hypothalamic (LH) areas. Groups of animals were then prepared in which a unilateral lesion in the PO area was combined with a contralateral lesion in the LH area. Plasma FFA response to 2-deoxyglucose in these rats was also blocked but not in rats having only unilateral lesions. The hyperglycemic response to 2-deoxyglucose was not affected in any of the experimental groups. These data suggest that a longitudinal pathway connecting PO, LH, and posterior hypothalamic areas is involved in FFA mobilization from adipose tissue in rats.     

The contralateral cortex contributes to the effects of hemidecortication on neuropeptide Y immunoreactivity in the rat striatum

We have previously shown that unilateral lesion by thermocoagulation of sensori-motor cortex which provides excitatory afferents to the striatum increases the number of neuropeptide Y (NPY)-immunoreactive neurons in the rat striatum. The present study examined whether this paradoxical effect is due to adaptive neuronal mechanisms involving the crossed projections from the contralateral spared cortex. To test this hypothesis, we compared the effects of unilateral and bilateral cortical lesions on the number of NPY-immunoreactive neurons in the striatum. Results showed that animals with bilateral lesion have no significant change in NPY immunoreactivity versus control suggesting that the contralateral intact cortex is responsible for the increase of NPY-immunoreactive neurons detected after unilateral lesion.     

Interruption of projections from the medial geniculate body to an archi-neostriatal field disrupts the classical conditioning of emotional responses to acoustic stimuli

We have previously found that the coupling of changes in autonomic activity and emotional behavior to acoustic stimuli through classical fear conditioning survives bilateral ablation of auditory cortex but is disrupted by bilateral lesions of the medial geniculate nucleus or inferior colliculus in rats. Auditory fear conditioning thus appears to be mediated by the relay of acoustic input from the medial geniculate nucleus to subcortical rather than cortical targets. Since the medial geniculate nucleus projects, in addition to auditory cortex, to a striatal field, involving portions of the posterior neostriatum and underlying archistriatum (amygdala), we have sought to determine whether interruption of connections linking the medial geniculate nucleus to this subcortical field also disrupts conditioning. The conditioned emotional response model studied included the measurement of increases in mean arterial pressure and heart rate and the suppression of exploratory activity and drinking by the acoustic conditioned stimulus following delayed classical conditioning, where the footshock unconditioned stimulus appeared at the end of the conditioned stimulus. The peak increase in arterial pressure and the duration of activity and drinking suppression were greater in unoperated animals subjected to delayed conditioning than in pseudoconditioned controls, where the footshock was randomly rather than systematically related to the acoustic stimulus. Increases in heart rate, however, did not differ in conditioned and pseudoconditioned groups. While the arterial pressure and behavioral responses therefore reflect associative conditioning, the heart rate response does not. Rats were prepared with bilateral lesions of the medial geniculate nucleus, bilateral lesions of the striatal field or asymmetrical unilateral lesions destroying the medial geniculate nucleus on one side and the striatal field on the contralateral side. The latter preparation leaves one medial geniculate nucleus and one striatal field intact but disconnected and thus produces a selective auditory deafferentation of the intact striatal field. Control groups included animals with unilateral lesion of the medial geniculate nucleus, with unilateral lesion of the medial geniculate nucleus combined with lesion of the ipsilateral striatal field, unilateral lesion of the medial geniculate combined with lesion of the contralateral anterior neostriatum (a striatal area outside of the medial geniculate nucleus projection field).(ABSTRACT TRUNCATED AT 400 WORDS)     

Maternal behavior in rats: evidence for the involvement of preoptic projections to the ventral tegmental area

This study provides evidence that a neural system extending from the preoptic region to the ventral tegmental area (VTA) of the midbrain is important for the normal expression of maternal behavior in lactating rats. In the first experiment, bilateral electrolytic lesions of the VTA severely disrupted the maternal behavior of postpartum rats. In the second experiment, lactating rats that received a unilateral knife cut severing the lateral connections of the medial preoptic area (MPOA) paired with a contralateral lesion of the VTA showed more severe maternal behavior deficits than females that received one of the following treatments: (a) a unilateral knife cut severing the lateral connections of the MPOA paired with an ipsilateral VTA lesion; (b) a unilateral knife cut severing the lateral connections of the MPOA paired with a contralateral lesion of the medial hypothalamus posterior to the MPOA; (c) a unilateral knife cut severing the lateral connections of the lateral preoptic area paired with a contralateral VTA lesion. The oral components of maternal behavior (retrieving and nest building) were particularly affected as a result of bilateral damage to the system extending from the preoptic area to the VTA.     

Inhibition of the substantia nigra suppresses absences and clonic seizures in audiogenic rats, but not tonic seizures: evidence for seizure specificity of the nigral control

GABAergic inhibition of the substantia nigra pars reticulata has been shown to suppress seizures in most models of epilepsy involving forebrain networks, such as absences or clonic seizures. No such antiepileptic effects were observed, however, in genetically audiogenic rats exhibiting tonic seizures generated in the brainstem. This suggests a constitutive dysfunction of the nigral GABAergic neurotransmission in this strain of rat or a selective action of the nigral control on specific networks. In the present study, we first confirmed that bilateral injection of muscimol (700 pmol/side) in the substantia nigra had no effect in Wistar rats with audiogenic seizures (Wistar AS). [3H]Muscimol autoradiography suggested a 40% reduced density of GABA(A) receptors in the substantia nigra of Wistar AS, whereas no change was observed in the cortex and the superior colliculus (superficial and intermediate layers), as compared to control animals. In Wistar AS where 40 repetitions of audiogenic stimulations progressively induced generalised convulsive seizures with both tonic and clonic components, bilateral injection of muscimol (350 pmol/side) in the substantia nigra suppressed the clonic component but had no effect on tonic seizures. In hybrid rats issued from cross-breeding between Wistar AS and rats with spontaneous absence seizures, bilateral injection of muscimol (18 pmol/side) in the substantia nigra abolished cortical spike-and-wave discharges, but had no effect on tonic audiogenic seizures at doses up to 700 pmol/side. These results show that despite a decreased number of GABA(A) receptors in the substantia nigra, inhibition of this structure in Wistar AS still leads to inhibition of seizures involving forebrain structures. These results confirm that GABAergic inhibition of the substantia nigra has antiepileptic effects through the control of forebrain circuits. They suggest that this control mechanism has no inhibitory effect on circuits underlying audiogenic tonic seizures.     

Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus

Rats (n = 11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n = 8) or unoperated (n = 5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions.     

Neurological correlates of unilateral and bilateral "strokes" of the middle cerebral artery in the rat.

Rats with unilateral lesions of the middle cerebral artery (MCA) were tested for the ability to detect (touch) and remove a square of adhesive tape from each forepaw, and for performance on a number of neurological tests (e.g., placing and hopping reflexes, activity). Rats with MCA damage showed deficits in both touching and removing the tape from the paw contralateral to the damage, but not ipsilateral to the damage, while performing within normal limits on the other tests. After scores of the MCA rats dropped into the control group range on the adhesive tape test, they sustained damage to the opposite MCA. This did not reinstate the original deficit, suggesting that the recovery seen after the unilateral lesion was not mediated by the opposite cortex. The second lesion, however, caused a deficit in removing the adhesive tape from the limb opposite the new stroke. Some of the rats that originally had sham operations received bilateral MCA lesions at this time. These animals showed much more severe deficits on the adhesive tape test than the rats with sequential strokes. Rats with bilateral MCA damage (simultaneous or sequential) also slipped on a long narrow plank more often than control animals. Nimodipine did not enhance recovery on any of the behavioral measures.     

Effects of discrete destruction of functionally identified chemosensitive hypothalamic neurons on ingestive behavior.

Food and water consumption and body weight were measured for 9 male albino rats prior to and following large unilateral electrolytic lesions of the lateral hypothalamus (LH) or adjacent structures. Eight of these animals with unilateral electrolytic lesions and 3 normal animals were then subjected to acute electrophysiological experiments in which chemosensitive neurons in the contralateral LH area were identified and tissue in the vicinity of these neurons was selectively destroyed. The one other animal with a unilateral electrolytic lesion was subjected to the acute electrophysiological experiment but selective tissue destruction was not made. In addition, a series of functional behavioral tests including the salt arousal of drinking, water deprivation induced drinking, food deprivation induced eating, water consumption in the absence of food, and food consumption in the absence of water were carried out for each animal prior to and following each lesion. Results indicate that the selective unilateral destruction of functionally identified chemosensitive LH neurons produces insignificant changes in the behaviors tested. Results are discussed in terms of the complexity of the LH neuropil and intact interconnections between the LH and mesencephalic reticular formation.     

The effect of embryonal amygdala grafts on the impairment of spatial working memory elicited in rats by kainate-induced amygdaloid damage

The effect of epileptogenic lesion of amygdala on spatial working memory was examined in rats after unilateral (U, n = 9) or bilateral (B, n = 8) injection of 1 or 0.5 mu of 0.2% kainate into the amygdaloid complex. Another group of unilaterally lesioned rats (T, n = 9) received 8 days after kainate injection grafts of embryonal (E 20) amygdala into the damaged region. Twelve days after lesion the three experimental groups and an unoperated control group (C, n = 11) were trained during three weeks in the aversively motivated 8-arm radial water maze (RWM). Training decreased incidence of errors/8 choices from the initial 2.3 to 1.2 in the lesioned rats and to 0.4 in the controls. Transplantation did not enhance RWM acquisition but restored the symmetrical pattern of choices and normalized the emotionality of lesioned animals. Retraining the RWM task 3 months later revealed significant savings in the control group but not in the transplanted group. Histology showed in addition to large lesion at the injection site also distant lesions in the ipsilateral hippocampus, thalamus and neocortex and in the unilaterally injected rats also in the contralateral amygdala. Healthy, well integrated transplants found in 6 out of 9 transplanted rats reduced the incidence of remote lesions (particularly in the contralateral hemisphere). Performance of individual animals reflected the state of the transplant. It is concluded that the impairment of spatial working memory is due not only to destruction of amygdala but also to diffuse damage of the limbic system. The slowly developing seizure-induced distant lesions can be partly prevented by embryonal grafts.     

Active avoidance in rats with unilateral hypothalamic and optic nerve lesions

During the height of the contralateral sensorimotor deficit that follows unilateral lateral hypothalamic lesions, rats demonstrate severe performance deficits when tested on a two-way active avoidance task which utilizes a visual conditioned stimulus. This deficit is observed whether or not the ipsilateral or contralateral optic nerve is sectioned in conjunction with the unilateral hypothalamic lesion. With the return of sensorimotor function contralateral to the lesion, animals that had been unable to avoid shock during their debilitated phase demonstrated significant savings when tested on the original task.     

Augmentation of ventral tegmental area stimulation-induced feeding by both stimulation and lesion of the contralateral ventral tegmental area in the rat

Unilateral lesions of the ventral tegmental area (VTA) facilitate behavioral responses (feeding and exploration) induced by electrical stimulation of the VTA in the contralateral hemisphere. It was hypothesized that this facilitation may result from a lesion-induced compensatory increase in dopamine transmission in the intact hemisphere. In the present study we tested on the functional level the hypothesis that the activity of bilateral mesocorticolimbic systems is inversely related. For this purpose we compared the effect of unilateral subthreshold activation with the effect of subsequent unilateral lesion of VTA on feeding response evoked by electrical stimulation of the contralateral VTA. In male Wistar rats implanted with bilateral VTA electrodes stimulation-induced feeding was tested in a latency to feed-stimulation frequency curve-shift paradigm. One electrode was used for induction of feeding reaction and the other electrode was used for concurrent stimulation (with the subthreshold current) and subsequent electrolytic lesioning of the contralateral VTA. It was found that both contralateral stimulation and subsequent lesion performed through the same electrode facilitated a feeding response that manifested as a decrease in the reaction's threshold and a leftward shift of the latency-frequency curve. The paradoxical similarity of the effects of the stimulation and lesion is discussed in terms of functional organization of the mesocorticolimbic system and adaptive changes in dopaminergic transmission.     

Functional compensation in the lateral suprasylvian visual area following bilateral visual cortex damage in kittens

Summary Previous studies have shown that functional compensation is present in the cat's posteromedial lateral suprasylvian (PMLS) area of cortex after damage to areas 17, 18, and 19 (visual cortex) early in life but not after damage in adults. These studies all have investigated animals with a unilateral visual cortex lesion, whereas all behavioral studies of compensation for early visual cortex damage have investigated animals with a bilateral lesion. In the present experiment, we investigated whether functional compensation also is present in PMLS cortex after a bilateral visual cortex lesion early in life. We recorded from single neurons in the PMLS cortex of adult cats that had received a bilateral lesion of areas 17, 18, and 19 on the day of birth or at 8 weeks of age. We found that PMLS cells in both groups of cats had functional compensation (normal direction selectivity and ocular dominance) similar to that seen after a unilateral lesion at the same ages. These results are consistent with the hypothesis that PMLS cortex is involved in the behavioral compensation seen after early visual cortex damage. In addition, the results indicate that inputs from contralateral visual cortex are not necessary for the development of functional compensation seen in PMLS cortex.     

Limb preference after lesions of the cerebral hemisphere in adult and neonatal rats

This experiment was designed to compare the effects of unilateral cortical ablation on limb preference in adult versus newborn rats. Postoperatively, all adult animals preferred the limb on the side ipsilateral to the lesion inspite of pre- and postoperative testing bias toward the contralateral limb. However, neonatal cortical lesions followed by similar testing at maturity resulted in a contralateral or ambilateral limb preference in half of the animals tested. These differences are discussed in terms of central nervous system plasticity.     

Recovery of sensorimotor function after frontal cortex damage in rats: evidence that the serial lesion effect is due to serial recovery

Multiple-staged brain lesions produce fewer and smaller behavioral effects than does damage produced in a single surgery. This is called the serial lesion effect. Two hypotheses were tested, the reduced deficit hypothesis and the serial recovery hypothesis, which attempt to explain the serial lesion effect. The effects of lesions of the medial frontal cortex on sensorimotor behavior were investigated in rats that received bilateral damage in a single surgery (n = 7), in two unilateral stages separated by 3 weeks (n = 16), or unilateral damage followed 3 weeks later by a sham surgery (n = 5). Unilateral damage produced deficits on the contralateral side in responsivity to visual, tactile, and olfactory stimuli and impairments in roll-over and paw withdrawal motor responses. All behavioral impairments except visual placement recovered over the next 3 weeks. A second unilateral lesion on the contralateral side produced the same symptoms but on the opposite side of the body. There was no reinstatement of the previously recovered deficits. Bilateral damage incurred in a single stage produced these same deficits on both sides. Because the effects of the second unilateral lesion in the two-stage group produced comparable contralateral effects to those produced in the single-stage group, but no reinstatement of ipsilateral deficits occurred, the reduced deficit hypothesis was rejected. It was concluded that at least for medial frontal cortex damage, the serial lesion effect occurred as a result of serial recovery of the deficits.     

Effects of LH kainic acid infusions on ingestion and autonomic activity

The effects of lateral hypothalamic (LH) infusions of kainic acid (KA) were determined on ingestive behavior, body weight, and motor and autonomic activity. In Experiment 1 male hooded rats received bilateral LH infusions of isotonic saline in volumes of 0.5 or 1.0 μl, 3.0 μg KA in volumes of 0.5 or 1.0 μl, or 6.0 μg of KA in a volume of 1.0 μl. All animals receiving 6.0 μg/1.0 μl of KA died. The 3.0 μg/0.5 μl dose resulted in transient decreases in food and water consumption and body weight. Animals receiving this dose no longer drank in response to 2 cc/kg 15% NaCl injections, exhibited attenuated drinking in response to 24 hr water and food deprivation, exhibited a transient decrease in eating following food deprivation and decreased eating following 750 mg/kg injections of 2-deoxy-D-glucose. Minimal effects on these measures were observed following the 3.0 μg/1.0 μl dose. In Experiment 2 rats received unilateral infusions of KA and the effects on motor and autonomic activity and ingestive behavior and body weight were compared to unilateral saline infused animals and animals with radiofrequency lesions. Only transient decreases in food consumption lasting 1–2 days were observed for both unilateral KA LH infused and lesioned animals. In KA infused rats contralateral exophthalamus, rapid shallow breathing, bilateral mydriasis, no contralateral pupillary constriction response, excessive salivation, body tremors, seizures, convulsions, teeth chattering, contralateral tail suspension induced spinning and turning, and elevated body temperature were observed for up to 6 hr following the infusion. Results are discussed in terms of lateral ventral diencephalic neurons involved in the more permanent deficits associated with bilateral LH damage.     

Behavioral recovery from unilateral photothrombotic infarcts of the forelimb sensorimotor cortex in rats: role of the contralateral cortex

During sensorimotor recovery following stroke ipsi- and contralesional alterations in brain function have been characterized in patients as well as animal models of focal ischemia, but the contribution of these bilateral processes to the functional improvement is only poorly understood. Here we examined the role of the homotopic contralateral cortex for sensorimotor recovery after focal ischemic infarcts at different time periods after the insult. One group of animals received a unilateral single photothrombotic infarct in the forelimb sensorimotor cortex, while four additional groups received a second lesion in the contralateral homotopic cortex either immediately or 2 days, 7 days, or 10 days after the first infarct. The time course of functional recovery of the impaired forelimbs was assessed using different sensorimotor scores: forelimb-activity during exploratory behavior and frequency of forelimb-sliding in the glass cylinder as well as forelimb misplacement during grid walking. Focal infarcts in the forelimb sensorimotor cortex area significantly impaired the function of the contralateral forelimb in these different behavioral tests. The subsequent damage of the contralateral homotopic forelimb sensorimotor cortex only affected the forelimb opposite to the new lesion but did not reinstate the original deficit. The time course of sensorimotor recovery after bilateral sequential cortical infarcts did not significantly differ from animals with unilateral single lesions. These data indicate that following small ischemic cortical infarcts in the forelimb sensorimotor cortex the contralateral cortex homotopic to the lesion plays only a minor role for functional recovery.     

The basolateral amygdala-ventral striatal system and conditioned place preference: further evidence of limbic-striatal interactions underlying reward-related processes.

The effects on the expression of a conditioned place preference of bilateral, excitotoxic amino acid-induced lesions of the basolateral region of the amygdala, or the ventral striatum, or asymmetric, unilateral lesions of both structures were studied. The place preference was conditioned by exposing hungry rats to sucrose in a distinctive environment. Following acquisition, bilateral quisqualate-induced lesions of the basolateral amygdala, as well as bilateral quinolinate-induced lesions of the ventral striatum, abolished the conditioned place preference. Bilateral ventromedial, but not dorsolateral, quinolinate-induced caudate-putamen lesions attenuated the place preference. Combining a unilateral lesion of the basolateral amygdala with a contralateral lesion of the ventral striatum also disrupted the conditioned place preference. These data provide further support for the hypothesis that the basolateral amygdala and ventral striatum are important parts of a neural system subserving stimulus-reward associations.