Injection Of Ibotenic Acid Research Articles

Effects of Partial Hippocampal Lesions by IbotenicAcid on Repeated Acquisition of Spatial Discrimination in Pigeons

Pigeons were trained on a spatial discrimination task using a repeated acquisition procedure. In this procedure, the pigeons were trained to discriminate between the positions of three keys. One of them was designated the correct key. When the subjects reached the criterion, the discrimination task was changed, with one of two previously incorrect keys now being made the correct key. This procedure was repeated at least 15 times. Then, lesions to the whole hippocampus, the medial hippocampus or to the lateral hippocampus were made by injections of ibotenic acid (Experiment 1). Only the subjects with damage to the whole hippocampus showed deficits in learning after the lesions. The deficits were similar to those caused by aspiration lesions /37/. Knife cuts separating the medial and lateral hippocampi were made in Experiment 2. The subjects did not show deficits in the spatial discrimination task after the sections. Although studies of the connectivity in the avian hippocampus suggested functional differences between the medial and lateral hippocampi, the present results show that pigeons can learn spatial discrimination with the medial and lateral parts of hippocampus separated.

Patterns of hippocampal cell loss based on subregional lesions of the hippocampus

It is widely accepted that the hippocampus plays an essential role in memory. Furthermore, studies have suggested that subregions within the hippocampus contribute differentially to specific behavioral components of memory. These studies typically rely on lesions produced by localized injections of neurotoxins (e.g., ibotenic acid or colchicine) into targeted subregions of the hippocampus. In the present study, the specificity of ibotenic acid lesions into areas CA1 and CA3 and colchicine lesions into the dorsal dentate gyrus (DG) was tested. Specifically, the effects of lesions within the dorsal hippocampus, the ventral hippocampus, and areas outside the hippocampus (e.g., lateral septum and entorhinal cortex) were evaluated using Fluoro-Jade, a histofluorescent stain for degenerating neurons. The results show that cell loss is relatively uniform after ibotenic acid injections into areas CA1 and CA3 and variable after colchicine injections into DG. CA1 and CA3 lesions appeared mostly localized to those relative subregions, and DG lesions appeared highly localized to the DG. Using these lesion procedures, little cell loss was apparent in the ventral hippocampus, and no cell loss was apparent in the entorhinal cortex. It is suggested that the lesion procedures described in this study produce relatively selective lesions of neurons within specific subregions of the hippocampus and should be useful for studies examining possible differential contributions of hippocampal subregions to memory processes.

Vestibular inputs to propriospinal interneurons in the feline C1-C2 spinal cord projecting to the C5-C6 ventral horn

The resting length of respiratory muscles must be altered during changes in posture in order to maintain stable ventilation. Prior studies showed that although the vestibular system contributes to these adjustments in respiratory muscle activity, the medullary respiratory groups receive little vestibular input. Additionally, previous transneuronal tracing studies demonstrated that propriospinal interneurons in the C(1)-C(2) spinal cord send projections to the ipsilateral diaphragm motor pool. The present study tested the hypothesis that C(1)-C(2) interneurons mediate vestibular influences on diaphragm activity. Recordings were made from 145 C(1)-C(2) neurons that could be antidromically activated from the ipsilateral C(5)-C(6 )ventral horn, 60 of which had spontaneous activity, during stimulation of vestibular receptors using electric current pulses or whole-body rotations in vertical planes. The firing of 19 of 31 spontaneously active neurons was modulated by vertical vestibular stimulation; the response vector orientations of many of these cells were closer to the pitch plane than the roll plane, and their response gains remained relatively constant across stimulus frequencies. Virtually all spontaneously active neurons responded robustly to electrical vestibular stimulation, and their response latencies were typically shorter than those for diaphragm motoneurons. Nonetheless, respiratory muscle responses to vestibular stimulation were still present after inactivation of the C(1)-C(2) cord using large injections of either muscimol or ibotenic acid. These data suggest that C(1)-C(2) propriospinal interneurons contribute to regulating posturally related responses of the diaphragm, although additional pathways are also involved in generating this activity.

Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

We determined if the dorsal raphe nucleus (DRN) exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11) or 1 microg/0.2 microl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10) through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment) and a low dose of dietary captopril (1 mg/g chow). From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 +/- 2.3 to 22.3 +/- 4.6 ml 0.3 M NaCl intake) whereas PB-DRN did not exceed 2 ml (P < 0.001). Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 +/- 3.8 vs 21.6 +/- 3.9 ml 300 min after fluid offer, P < 0.001). Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 +/- 4.3 and 32.5 +/- 3.4 ml on day 1 and day 2, respectively, vs 20.2 +/- 2.8 ml on day 0, P < 0.001). These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus

This experiment tested the involvement of the ventromedial hypothalamus (VMH) in the sympathetic and hyperthermic reactions induced by an intracerebroventricular (i.c.v.) injection of orexin A (1.5 nmol). In the first part of the experiment, the firing rate and cytochrome oxidase activity of the VMH neurons, and the colonic temperature were monitored in 12 urethane-anaesthetized rats before an i.c.v. injection of orexin and over a period of 2 h after the injection. Orexin induced an increase in the firing rate, colonic temperature and cytochrome oxidase activity. A group of 12 rats was used as a control: saline, but not orexin, was injected. No modifications in the firing rate, cytochrome oxidase reactivity and colonic temperature were noted. In the second part of the experiment, 12 rats were anaesthetized and lesioned bilaterally in the VMH with an injection of ibotenic acid. Sham lesions were carried out in 12 control rats. After 48 h, all animals were anaesthetized with ethyl-urethane. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored before and over a period of 2 h after an i.c.v. injection of orexin or saline in the lesioned and sham-lesioned rats. Orexin increased the sympathetic firing rate, IBAT and colonic temperatures and heart rate in the sham-lesioned rats. These increases were reduced by lesion of VMH. Saline did not induce any modification. These findings indicate that the VMH is involved in the control of the orexin-induced hyperthermia.

Differential effects of infralimbic cortical lesions on temperature and locomotor activity responses to feeding in rats

The time of food availability induces important behavioral and metabolic adaptations. Animals subjected to feeding restricted to a few daytime hours show increased locomotor activity and body temperature in anticipation of mealtime. In addition, animals under ad libitum feeding show a marked postprandial raise in body temperature and in thermogenesis. The areas of the brain commanding these responses to food are partially known. We investigated in the rat the role of the infralimbic area, located in the medial prefrontal cortex, and considered a visceral–autonomic motor area, in the responses to ad libitum or restricted feeding schedule. We performed infralimbic cortex excitotoxic lesions using injections of ibotenic acid, and measured body temperature and locomotor activity by telemetry in rats under ad libitum and restricted feeding conditions. We found that bilateral infralimbic area lesions prevented both the anticipatory and the postprandial increases in core temperature, decreased mean temperature by nearly 0.3°C during both light/dark phases, and increased daily temperature variability. In contrast, the lesion caused a rapid induction of the anticipatory locomotor activity. These results show that behavioral and metabolic responses to the time of food availability are commanded separately and that the infralimbic area is a key structure to adjust the body temperature to an upcoming meal.

モリス型水迷路課題の学習に及ぼすラット海馬ＣＡ１損傷の効果

It is known that the multiple injections of ibotenic acid to the hippocampal CA1 (Cornu Ammonis 1) field of a rat cause cell loss and spatial learning impairment in the place task of Morris water maze. However, no study seems to have been conducted concerning the cue task of the maze. This study examined (1) whether cell loss in the CA1 field produced learning deficits in both the place and cue tasks; (2) whether training could remedy the deficit in spatial learning; and (3) whether the order of place training and cue training could change the performance outcome. Thirty-seven rats of Wistar strain were divided into Place-Cue (PC) group that received place training first and then cue training, and Cue-Place (CP) group that received training in the reverse order. Half rats in each group were damaged in the CA1 field by ibotenic acid injections. Results indicated that damage to CA1 pyramidal cells led to performance deficits only in the place task throughout training, regardless of the sequence of training. The results also indicated that training in the prior task affected learning in the succeeding task, only at the beginning of training, and the effect is transient.

Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe

Our aim was to determine the effects of carotid body denervation (CBD) on the ventilatory responses to focal acidosis and ibotenic acid (IA) injections into the medullary raphe area of awake, adult goats. Multiple microtubules were chronically implanted into the midline raphe area nuclei either before or after CBD. For up to 15 days after bilateral CBD, arterial PCO2 (PaCO2) (13.3 +/- 1.9 Torr) was increased (P < 0.001), and CO2 sensitivity (-53.0 +/- 6.4%) was decreased (P <0.001). Thereafter, resting PaCO2 and CO2 sensitivity returned (P <0.01) toward control, but PaCO2 remained elevated (4.8 +/- 1.9 Torr) and CO2 sensitivity reduced (-24.7 +/- 6.0%) > or =40 days after CBD. Focal acidosis (FA) at multiple medullary raphe area sites 23-44 days post-CBD with 50 or 80% CO(2) increased inspiratory flow (Vi), tidal volume (Vt), metabolic rate (VO2), and heart rate (HR) (P <0.05). The effects of FA with 50% CO2 after CBD did not differ from intact goats. However, CBD attenuated (P <0.05) the increase in Vi, Vt, and HR with 80% CO2, but it had no effect on the increase in VO2. Rostral but not caudal raphe area IA injections increased Vi, BP, and HR (P < 0.05), and these responses were accentuated (P <0.001) after CBD. CO2 sensitivity was attenuated (-20%; P <0.05) <7 days after IA injection, but thereafter it returned to prelesion values in CBD goats. We conclude the following: 1) the attenuated response to FA after CBD provides further evidence that the carotid bodies provide a tonic facilitory input into respiratory control centers, 2) the plasticity after CBD is not due to increased raphe chemoreceptor sensitivity, and 3) the "error-sensing" function of the carotid body blunts the effect of strong stimulation of the raphe.

Ontogenic study of the influence of tissue plasminogen activator (t-PA) in neonatal excitotoxic brain insult and the subsequent microglia/macrophage activation

Intracerebral injections of ibotenic acid in neonatal mice produced white and gray matter lesions that mimic some aspects of the acquired cerebral injuries observed in human newborns (i.e. periventricular leukomalacias in preterm newborns and post-ischemic cortical necrosis in at term infants). We have evaluated the effects of tissue plasminogen activator inactivation (t-PA −/−) on the effects of ibotenic acid (0.01–20 μg), and on F4/80 labeling of microglia/macrophages at different stages. Three ontogenic periods have been identified. In mice injected the day of birth, postnatal (P) day 0, ibotenic acid induced neuronal migration disorders together with low local microglial activation in wild-type and t-PA −/− mice. In P2 and P5 mice, ibotenic acid induced diffuse microglial activation in the whole cortex and subcortical areas; e.g. caudate nucleus and septum. In wild-type mice, cystic lesions of the white matter were consistently observed, surrounded by macrophages. In t-PA −/− mice, noncystic lesions filled of macrophages were more frequent than cysts. Macrophages were virtually absent in the gray matter. White and gray matter lesions were reduced in t-PA −/− mice. The plasmin inhibitor aprotinin reduced white and gray matter lesions only in wild-type mice injected with high ibotenic acid doses (2.5–5 μg). During this period, a transient F4/80 immunoreactive cell population was detected in the cingulum. At P10, the salient lesion characteristic was a large gray matter lesion containing macrophage accumulation. Microglial activation was confined to the injection site in the white matter. t-PA −/− mice showed reduced lesion size under high doses (>5 μg) of ibotenic acid. Similarly, aprotinin diminished the lesion in wild-type animals exposed to 10 μg ibotenic acid. These data demonstrate that t-PA and microglia do not actively participate in the migration disorders induced in P0 mice. Conversely, t-PA was implicated in cyst formation in older (P2-P10) mice, and in their subsequent growth. t-PA was also involved in GM lesions, probably through an inflammatory process involving macrophages.

Glial overexpression of heme oxygenase-1: a histochemical marker for early stages of striatal damage

The level of heme oxygenase-1 (HO-1) in the normal striatum is below the limit of immunodetection. However, HO-1 is overexpressed in both neural and non-neural cells in response to a wide range of lesions. We induced different types of lesions affecting the striatal cells or the main striatal afferent systems in rats to investigate if overexpression of HO-1 could be a useful histochemical marker of striatal damage. Thirty-six hours after intrastriatal or intraventricular injection of excitotoxins that affect striatal neurons (ibotenic acid) or of neurotoxins that affect striatal dopaminergic (6-hydroxydopamine) or serotonergic (5,7-dihydroxytriptamine) afferent terminals, or after surgical lesioning of cortico-striatal projections, there was intense induction of striatal HO-1 immunoreactivity (HO-1-ir). Double immunolabeling revealed that the HO-1-ir was located in glial cells. After intrastriatal injection of ibotenic acid, a central zone of neuronal degeneration contained numerous round and pseudopodic HO-1-ir cells, and was surrounded by a ring of HO-1-ir cells, most of which were immunoreactive for astroglial markers. Intraventricular injection of neurotoxins induced astroglial HO-1-ir cells which were more evenly distributed throughout the lesioned or denervated areas. HO-1-ir microglial cells were also observed in areas subjected to mechanical damage. The HO-1-ir was markedly lower or absent 1 week after lesion, and even more so 3 weeks after, although some HO-1-ir cells were still observed after intrastriatal injection of ibotenic acid or surgical corticostriatal deafferentation. The results indicate that determination of glial HO-1-ir is a useful histochemical marker for early stages of striatal damage.

Effect of acamprosate on neonatal excitotoxic cortical lesions in in utero alcohol-exposed hamsters

Alcohol exposition during pregnancy has irreversible effects on the fetus brain. In hamsters, intrapallial injection of the glutamate receptor agonist ibotenic acid (100 ng) on the day of birth (P0) induced neuronal migration disorders. In utero alcohol (7%) exposure from day 5 of gestation to P5, enhanced lesions size measured in pups’ brain at P5. The administration for the same period of the taurine derivative acamprosate together with alcohol or in water to pregnant females reduced the rate of occurrence of nodular heterotopia, sub-pial ectopia and microgyria in non-alcohol-exposed pups. In addition acamprosate diminished lesion size in alcohol-exposed and non-exposed pups. A significant dose-related effect of acamprosate was observed. In addition, acamprosate rescued 27% of the pups injected with 10 μg ibotenic acid, a lethal dose in alcohol-exposed animals.

Hypothalamic paraventricular nucleus neurons regulate medullary catecholamine cell responses to restraint stress.

Both physical and psychological stressors recruit catecholamine cells (CA) located in the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS). In the case of physical stressors, this effect is initiated by signals that first access the central nervous system at or below the level of the medulla. For psychological stressors, however, CA cell recruitment depends on higher structures within the neuraxis. Indeed, we have recently provided evidence of a pivotal role for the medial amygdala (MeA) in this regard, although such a role must involve a relay, as MeA neurons do not project directly to the medulla. However, some of the MeA neurons that respond to psychological stress have been found to project to the hypothalamic paraventricular nucleus (PVN), a structure that provides significant input to the medulla. To determine whether the PVN might regulate medullary CA cell responses to psychological stress, animals were prepared with unilateral injections of the neurotoxin ibotenic acid into the PVN (Experiment 1), or with unilateral injections of the retrograde tracer wheat germ agglutinin-gold (WGA-Au) into the CA cell columns of the VLM or NTS (Experiment 2). Seven days later, animals were subjected to a psychological stressor (restraint; 15 minutes), and their brains were subsequently processed for Fos plus appropriate cytoplasmic markers (Experiment 1), or Fos plus WGA-Au (Experiment 2). PVN lesions significantly suppressed the stress-related induction of Fos in both VLM and NTS CA cells, whereas tracer deposits in the VLM or NTS retrogradely labeled substantial numbers of PVN cells that were also Fos-positive after stress. Considered in concert with previous results, these data suggest that the activation of medullary CA cells in response to psychological stress may involve a critical input from the PVN.

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats.

In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex (pre-BötzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BötzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-BötzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/- 10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately 60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (approximately 90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-BötzC area were lesioned in these goats. We conclude that, in the awake state, the pre-BötzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-BötzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.

Stressor-selective role of the ventral subiculum in regulation of neuroendocrine stress responses.

The ventral subiculum (vSUB) confers inhibitory effects of the hippocampus on hypothalamo-pituitary-adrenocortical (HPA) axis responses to novelty and restraint. The current study was designed to evaluate the role of the vSUB in regulating HPA axis responses to stressors of diverse modalities. Male Sprague Dawley rats received bilateral ibotenic acid or saline injections into the region of the vSUB. Corticosterone secretion was assessed after exposure to hypoxia and elevated plus maze, with the two stress exposures occurring 5 d apart. Peak corticosterone responses to hypoxia were reduced in vSUB-lesion animals, indicating an attenuation of HPA axis responsiveness. A subsequent study revealed that hyporesponsivity to hypoxia was evident in chamber-naive as well as chamber-adapted animals, verifying that this effect was independent of previous experience in the testing environment. In contrast, the effects of vSUB lesions on corticosterone responses to the elevated plus maze exposure were substantially more circumspect, being limited to a slight increase in secretion at the 2-h poststress time point. The limited vSUB lesion-induced increase in the plasma corticosterone response to elevated plus maze exposure occurred despite an increased open-arm time in the maze, suggesting that lesions reduced anxiety-like behavior. In combination with previous studies, these data suggest that the vSUB has excitatory as well as inhibitory input into HPA axis responsivity, depending on the nature of the stressful stimulus, and suggest that behavioral and neuroendocrine responses to stressful or anxiogenic stimuli may be dissociable.

Dietary restriction differentially protects from neurodegeneration in animal models of excitotoxicity

Reduced caloric intake obtained through long-term dietary restriction has been found beneficial in some animal models of neurodegeneration. We report here that rats maintained under dietary restriction from the second to the eighth month of age are fully protected towards degeneration of GABAergic neurons in the hippocampus and the olfactory-entorhinal cortex caused by systemic administration of the convulsant toxin, kainic acid. However, in a different model of excitotoxic neurodegeneration, injection of ibotenic acid in the forebrain magnocellular basal nucleus, the decrease of a cholinergic marker in the target areas of the cortex was only partially protected by dietary restriction. Thus, in different experimental models neurodegeneration can be differentially rescued by dietary restriction. Analysis of alterations in the expression of relevant genes in different experimental conditions, could help in better understanding these differences.

Ectopic parvalbumin expression in mouse forebrain neurons increases excitotoxic injury provoked by ibotenic acid injection into the striatum

A neuroprotective role for Ca 2+-binding proteins in neurodegenerative conditions ranging from ischemia to Alzheimer's disease has been suggested in several studies. A key phenomenon in neurodegeneration is the Ca 2+-mediated excitotoxicity brought about by the neurotransmitter glutamate. To evaluate the relative ability to resist excitotoxicity of neurons containing the slow-onset Ca 2+-binding protein parvalbumin (PV), we injected the glutamate agonist ibotenic acid (IBO) into the striatum of adult mice ectopically expressing PV in neurons. Striatal ibotenic acid injection results in local nerve cell loss and reactive astrogliosis. Light microscopic evaluation, carried out after a delay of 2 and 4 weeks, reveals an enlarged and accelerated neurodegenerative process in mice ectopically expressing neuronal PV. Thus, PV is not neuroprotective, it rather enhances nerve cell death. This result implicates that the increase in cytosolic Ca 2+-buffering capacity in the transgenic mice impairs other systems involved in Ca 2+ sequestration. In addition, ultrastructural morphometric analysis shows that in neurons the mitochondrial volume is reduced in mice ectopically expressing neuronal PV. This is paralleled by a reduction in the amount of the mitochondrial marker enzyme cytochrome c oxidase subunit I (COXI). We conclude that alterations in the Ca 2+ homeostasis present in mice ectopically expressing neuronal PV are more deleterious under excitotoxic stress and largely outweigh the potential benefits of an increased Ca 2+-buffering capacity resulting from PV.

Neuroplasticity in the cat's visual system: test of the role of the expanded retino-geniculo-parietal pathway in behavioral sparing following early lesions of visual cortex.

Sparing of the ability to redirect head and eyes to new stimuli and expansion of the retino-geniculo-parietal pathway are both robust aspects of the repercussions of early lesions of occipital visual areas in cats. The purpose of the present work was to test the proposition that the pathway expansions and spared behaviors are causally linked. The proposition was tested by deactivating either the dorsal lateral geniculate nucleus (dLGN) and thereby uncoupling the primary and secondary limbs of the retino-geniculo-parietal pathway, or silencing the terminus of the pathway, and then testing the ability of cats to detect and orient head and eyes to visual targets. Six cats sustained experimental unilateral lesions of occipital areas 17 and 18 and variable amounts of area 19 on postnatal days 1-2 or 26-30 to induce rewiring and expansion of visual pathways from retina through the dLGN onto a critical region of visuoparietal (VP) cortex. Unilateral lesions ensured that we could use the orienting performance of the intact hemisphere as a fiduciary marker of performance against which performance of the experimental hemisphere could be gauged. When the cats were adult, a secondary test lesion was made on the damaged side by injecting, under electrophysiological guidance, ibotenic acid into either dLGN of four cats or into VP cortex of two cats. Prior to injection of ibotenic acid, all cats oriented head and eyes with high proficiency throughout the contralesional field, and performance was indistinguishable from orienting to stimuli presented in the ipsilesional field; sparing of the orienting behavior was complete. Ibotenic acid lesions of both dLGN and VP cortex induced a profound neglect of stimuli introduced into the contralesional hemifield. Orienting into the ipsilesional field remained high throughout. Subsequently, there was restoration of orienting behavior over the next 4-6 (dLGN deactivation) and 9-12 (VP deactivation) days. The test results demonstrate the essential contribution made by the retino-geniculo-parietal pathway to the ability to detect and redirect head and eyes to look at visual stimuli following early lesions of occipital visual cortices. The subsequent post-test lesion restoration of high orienting proficiency shows that in the absence of dLGN, or the critical region of VP cortex, other regions of cerebral cortex, or other structures such as the superior colliculus, can emerge and make important contributions to orienting behavior. These results reveal a maintained residual, beneficial adaptive plasticity of mature neural circuits even in brains compromised by early lesions of occipital visual areas.

The fate of hippocampal argyrophilic dark neurons after two kinds of brain insults; ibotenic acid injection and stressful swimming

The fate of hippocampal argyrophilic dark neurons after two kinds of brain insults; ibotenic acid injection and stressful swimming

Post-pubertal adrenergic changes in rats with neonatal lesions of the ventral hippocampus

Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal alterations in a number of cognitive, social and motor behaviors that bear some analogy to schizophrenia. Increased sensitivity to stress and psychostimulants and prefrontal functional changes in the lesioned animals suggest an involvement of the mesocorticolimbic dopamine (DA) system. DA and norepinephrine (NE) interact in a number of ways in the medial prefrontal cortex (mPFC) to influence each other’s functions. In order to assess the role of adrenergic system in the behavioral responses of neonatal VH (nVH) lesioned animals, we first examined cortical and subcortical bindings of alpha-1 and alpha-2 adrenergic receptors using [ 3H]-prazosin and [ 3H]-rauwolscine respectively, and the norepinephrine transporter (NET) using [ 3H]-nisoxetine. Sprague-Dawley rat pups, at post-natal day (PD) 7, received bilateral injections of ibotenic acid in the VH and were sacrificed pre (PD35)- and post (PD56)-pubertally. A significant increase in [ 3H]-prazosin binding was observed in the frontal and cingulate cortices of lesioned rats at PD56 without any significant change in the caudate putamen or nucleus accumbens. No significant difference was seen in [ 3H]-rauwolscine binding. A significant upregulation of NET binding was observed in subregions of the PFC and nucleus accumbens of PD56 lesioned rats. The functional relevance of changes in adrenergic markers on amphetamine-induced locomotor activity was examined by pre-treatment of PD56 rats with prazosin, an alpha-1 receptor antagonist. Prazosin at doses of 1.0 or 2.0 mg/kg ip significantly reduced amphetamine-induced locomotion in sham but not in PD56 lesioned animals. Taken together, these results suggest that alterations in prefrontal alpha-1 receptors likely contribute to altered behavioral responses observed in post-pubertal VH lesioned rats.

Lesions of the diagonal band of broca enhance drinking in the rat.

This study examined the role of the diagonal band of Broca (DBB) in drinking behaviour and vasopressin release. Adult male rats were anaesthetized (pentobarbital 50 mg/kg) and received DBB injections of either ibotenic acid (0.5 microl of 5 micro g/ microl) or vehicle (0.5 microl of phosphate-buffered saline). Although baseline drinking and urine output were not affected, drinking to 30% polyethylene glycol (MW 8000; 1 ml/100 g s.c.) and angiotensin II (0, 1.5 and 3.0 mg/kg s.c.) were significantly increased in ibotenic acid in phosphate-buffered saline (DBBX) rats. Drinking to hypertonic saline (0.9, 4 and 6%; 1 ml/100 g), and water deprivation were not significantly affected. DBBX rats had significantly lower basal heart rates than controls but the cardiovascular responses to infusions of angiotensin II (100 ng/kg/min i.v. for 45 min) were not affected. DBBX rats had significantly higher basal vasopressin, but angiotensin-stimulated vasopressin release was not significantly different. Although the DBB is not involved in basal water intake, it is involved in dipsogenic responses to hypovolemic stimuli and possibly basal autonomic function and basal vasopressin release.