Visual cortical plasticity following unilateral sensorimotor cortical lesions in the neonatal rat

Previous work has shown that unilateral sensorimotor cortex (SMC) lesions in newborn rats resulted in an apparent shift of the motor cortex map in the spared hemisphere, particularly of the hindlimb cortex. In view of such findings, the present study was initiated to determine if the visual cortex located both ipsilateral and contralateral to neonatal SMC, or contralateral to occipital cortical (OC) lesions, would show similar remodeling. Visual evoked potentials (VEPs) were used to map the visual cortex electrophysiologically. The results show an expansion of the visual cortex, in both the contralateral and ipsilateral hemisphere, into normally motor cortical areas in adult animals that had sustained unilateral neonatal unilateral SMC lesions. In contrast, similar changes were not seen within the spared visual cortex after unilateral occipital cortical lesions, suggesting that the shift in the visual map was specifically in response to the SMC lesion and was not a generalized response to neonatal cortical damage. Histological analysis showed a functional expansion in the rostral boundary of visual cortex with no corresponding cytoarchitectural alterations.     

Effects of ethanol on rat somatosensory cortical neurons

In this study, we characterized the local effects of ethanol (EtOH) on postsynaptic potentials (PSPs) and membrane properties of layer II–III (L2–3) and layer V (L5) somatosensory cortical neurons. Intracellular recordings were done using the in vitro slice preparation of rat somatosensory cortex. Our results show that EtOH exerts local effects on cortical cell membrane at physiologically relevant concentrations. A predominant effect of EtOH was to reduce excitability of L2–3 and L5 neurons by increasing the rheobase, decreasing input resistance and repetitive firing, reducing PSPs amplitude and the probability of evoking action potentials. Early (6 ms) and late (18 ms) PSP components were affected differentially by EtOH, the late components being more suppressed. Overall, EtOH-mediated suppression of PSPs was stronger in L5 neurons. Cortical neurons were divided into three subtypes: regular spiking adapting (RS-A), regular spiking non-adapting (RS-NA) and bursting (D-IB) neurons. PSPs evoked in RS-A neurons were more sensitive to EtOH suppressant effects. EtOH effects on input resistance were distributed differentially among the three groups of neurons. These results support the notion that EtOH disrupts higher processing of somatosensory information via a differential alteration of cortical neuron's membrane properties and synaptic transmission.     

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.     

Monocular pattern discrimination learning after unilateral lesions of anteromedial cortex in rat

Monocularly patched rats were trained on a series of visual tilt discriminations ordered from simple to difficult to measure the angular difference threshold of each eye. Preoperatively there was no difference between discrimination performance for either eye. Unilateral lesions of anteromedial cortex did not alter the monocular angular difference threshold. However, there was a reduction in discrimination performance for all angular difference comparisons. Animals showed a visual neglect for stimuli in the field contralateral to the lesion. The neglect was independent of the eye used for the discrimination.     

Effects of prefrontal cortical lesions on neuropeptide and dopamine receptor gene expression in the striatum-accumbens complex

In the rat, neurochemical, behavioral, and anatomical investigations suggest that medial prefrontal cortical input modulates the activity of the basal ganglia. To understand how prefrontal dysfunction might alter striatal-accumbens function, in situ hybridization histochemistry with S³⁵-labeled oligonucleotide probes was used to assess changes in striatal-accumbens gene expression following bilateral excitotoxic ibotenic acid (IA) lesions of the rat medial prefrontal cortex. Quantitative densitometry was used to measure changes in mRNA levels for preproenkephalin A (ENK), D1 dopamine receptor, protachykinin (SubP), glutamic acid decarboxylase (GAD65), and D2 dopamine receptor. No differences were found between sham and lesion groups for ENK, D1, SubP, or GAD65 mRNA levels in the striatum or nucleus accumbens (NAC). D2 receptor mRNA levels were, however, significantly higher in the dorsomedial striatum and in the core area of the NAC of the lesioned rats. Although the functional significance of increased D2 mRNA is unclear, these findings demonstrate that glutamate mPFC projections modulate gene expression in relatively regionally-localized subcortical neuronal populations.     

Movement-associated cortical potentials in unilateral cerebral lesions

Summary Movement-associated cortical potentials (MP) associated with thumb-opposition or fist-clenching were studied in 20 patients with unilateral cerebral lesions and in 8 healthy subjects. MP was abnormal in 16 patients. The most frequent abnormality was an attenuation of the N component or readiness potential, recorded on the central region contralateral to the contracting muscle, on the affected hemisphere. The occurrence and severity of MP abnormalities seem to be influenced by an intensity and extension of the lesion, rather than by how much disability is present in the affected limb. There was no significant correlation between the abnormalities of MP and of EEG. The most useful index of MP for comparing two hemispheres was shown to be the amplitude and wave form of the N component or readiness potential contralateral to the contracting muscle.

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Zusammenfassung Corticale Potentiale, assoziiert mit Daumenopposition oder Faustmachen, wurden bei 20 Patienten mit unilateralen cerebralen Läsionen und bei 8 gesunden Männern studiert. Die bewegungsassoziierten, cerebralen Potentiale (MP) waren abnorm bei 16 Patienten. Die häufigste Abnormität war eine Depression der N-Komponente oder des Bereitschaftspotentiales, registriert über der Zentralregion kontralateral zum zusammenziehenden Muskel über der beschädigten Hemisphäre. Vorkommen und Grad der MP-Abnormitäten schienen mehr von einer Intensität und Extension der Läsion als von einem Störungsgrad der gestörten Hand beeinflußt zu sein. Keine bedeutende Korrelation war vorhanden zwischen den MP-Abnormitäten und den EEG-Abnormitäten. Der wirksamste Index der MP zum Vergleich beider Hemisphären war eine Amplitude und Wellenform der N-Komponente oder des Bereitschaftspotentiales kontralateral zum zusammenziehenden Muskel.

     

Effects of unilateral lesions of auditory cortex on brain stem thresholds for electrical stimulation

Data are presented from a total of 28 electrodes which were permanently implanted in six cats in cochlear nucleus, medial geniculate body, and nonauditory loci. Behaviorally measured detection thresholds for electrical stimuli applied through the electrodes were obtained prior to and after unilateral ablation of auditory cortex. The principal results were that detection thresholds were elevated after the lesion for 7 of 11 placements in the medial geniculate body, for three of nine placements in the cochlear nucleus or cochlear nerve root, and for none of the placements in the visual system. The threshold increases for four of the medial geniculate electrodes could be accounted for in terms of retrograde degeneration in the vicinity of the electrode tip. Other threshold increases, particularly those for placements in or near the cochlear nucleus, are interpreted in terms of a functional disturbance in the auditory system that resulted from the cortical lesion.     

The effect of unilateral anteromedial cortex lesions on prey-catching and spatio-motor behaviour in the rat

The neglect which follows a unilateral lesion of anteromedial cortex in rat was examined using two tasks. In the first task animals had to press the left bar of a two-bar Skinner box for food reward. In the second task animals captured live locusts presented in either their right or left visual field. The results showed that in the Skinner box there was a transitory spatial neglect contralateral to the lesion, which disappeared after 2-3 days. In the prey-catching task animals failed to target or track locusts when they were in the field contralateral to the lesion throughout the 4-day testing period. Capture and consummatory responses were normal when the locust was presented (or moved independently) into the ipsilateral (non-neglected) field. 60 days later the asymmetrical response to locusts in the contralateral field had disappeared.     

Use-related gene expression patterns of rat motor cortex

Current evidence indicates reorganization of motor cortex in association with motor behavior. To investigate the molecular basis for these changes rats were fitted with limb-restricting vests which forced the use of one forelimb for 10 days. Using cDNA macroarrays, expression profiles of the corresponding motor cortices connected to the overused and immobilized limbs were analyzed. In the overused motor cortex up-regulations were observed exclusively, including genes coding for voltage-gated ion channels, trafficking and targeting proteins, and intracellular kinase network members (10 genes). In the contralateral immobilized cortex changes were restricted to down-regulation, mainly involving genes pertaining to DNA-binding, translation, neuronal signaling and metabolic pathways (9 genes). At least some of these changes are likely to represent the molecular substrate of use-dependent plasticity.     

Effects of vibrissae removal on methamphetamine-induced damage to rat somatosensory cortical neurons

Repeated methamphetamine (mAMPH) damages forebrain monoamine terminals and causes degeneration of nonmonoaminergic cell bodies in rat primary somatosensory cortex (S1). These degenerating cortical neurons can be labeled with the fluorochrome dye Fluoro-Jade (FJ) and are found almost exclusively in layers II/III and IV of the vibrissae representation in S1. Within S1, layer IV is organized into discrete, anatomically identifiable units termed barrels, each of which receives information from a single whisker. We previously reported that mAMPH-damaged neurons in S1 were located within the whisker barrels, suggesting that the prolonged mAMPH-induced whisking contributes to S1 neuronal injury. Here, we investigate effects of vibrissae removal on mAMPH-induced damage to S1 neurons. Rats were anesthetized and vibrissae were trimmed from either the left, right, or neither side of the snout. The next day they were given four injections of either saline (1 ml/kg, s.c.) or mAMPH (4 mg/kg, s.c.) at 2-h intervals. Three days later, cortical sections were processed for FJ histochemistry. The hemivibrissotomy produces a hemispheric asymmetry in FJ-positive neurons in barrel cortex, with fewer damaged neurons contralateral than ipsilateral to whisker removal. Taken together with the demonstration that acute injection of this dose of mAMPH induces the immediate early gene zif/268 and Fos protein in barrel cortex, these data suggest that the prolonged behavioral activity involving the vibrissae contributes to the mAMPH-induced damage to S1 neurons. Thus, some of the injurious effects of drugs may depend on afferent activity occurring as a result of the abnormal behaviors evoked by their administration.     

Scopolamine facilitates recovery of function following unilateral electrolytic sensorimotor cortex lesions in the rat

Following brain injury there is an excessive release of excitatory neurotransmitters that may lead to secondary cell death. Although much research has focused on glutamate-NMDA receptor interactions, acetylcholine-muscarinic receptor interactions may also prove to be important for an understanding of the pathophysiological events that lead to secondary degeneration after brain damage. Previous experiments have shown that the muscarinic receptor antagonist scopolamine facilitates recovery from very transient (1 h-10 days) behavioral deficits after fluid percussion injury. The present study extends these findings by investigating whether scopolamine can facilitate recovery from the more enduring behavioral deficits (14-60 days) that follow electrolytic lesions of the rat somatic sensorimotor cortex (SMC). Rats received unilateral lesions of the SMC and a regimen of scopolamine (1 mg/kg) or saline beginning 15 min after surgery. Following SMC lesions rats exhibited an impairment in placing the forelimb contralateral to the lesion as well as an ipsilateral somatosensory asymmetry on a bilateral tactile stimulation test. Rats treated with scopolamine showed a reduction in the initial magnitude of the contralateral placing deficit and an accelerated rate of recovery compared with saline-treated control rats. In contrast, scopolamine had no effect on recovery from the ipsilateral somatosensory asymmetry. These data are consistent with the idea that muscarinic receptor stimulation plays a role in the production of secondary brain damage, that blockade of this receptor leads to a facilitation of recovery on some behavioral tasks, and that electrolytic lesions may trigger some of the same posttraumatic events described in other models of neural trauma.     

Age-related variations in plasticity of rat basal forebrain cholinergic neurons after cortical lesions

The enzymatic activity of choline acetyltransferase (ChAT) in the nucleus basalis (NBM) of young rats (30 days old at the time of the operation) drops by 50% thirty days after cortical damage. This is followed by a spontaneous recovery of the enzymatic activity at 120 days after the lesion. In the present study, similar changes were observed in rats which were lesioned at maturity (4 months old). However, a different response was noted when surgery was performed on aged rats (2 years old at the time of operation). In these aged rats the drop in enzymatic activity in the NBM at 30 days post-lesion was as marked as in the young and mature animals, and no recovery was observed, even at 120 days. These results are discussed in the context of age-related neurodegenerative disease with cholinergic involvement.     

Changes in cortical and subcortical levels of monoamines and their metabolites following unilateral ventrolateral cortical lesions in the rat

Suction lesions were made in the anterior, posterior or both halves of the right ventrolateral cortex in rats. Six days later, levels of the monoamine neurotransmitters, norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in cortical and subcortical regions of lesioned rats and compared to values in sham-operated animals. NE and 5-HT were decreased in sections of ipsilateral (right) cortex including, and posterior to lesions, while 5-HIAA was increased throughout the ipsilateral cortex. Decreases in monoamines and increases in metabolites and metabolite:monoamine ratios (especially 5-HIAA:5-HT) were found in ipsilateral subcortical structures, including striatum, nucleus accumbens, hippocampus, hypothalamus, midbrain and brainstem, depending on the type of lesion. Subacutely, focal ventrolateral cortical lesions may profoundly alter the levels and utilization rates of monoamine neurotransmitters in widespread regions of the ipsilateral hemisphere.     

Ontogeny of cholecystokinin gene expression in the rat thalamus--a hybridization histochemical study

We examined the ontogeny of cholecystokinin (CCK) gene expression in the rat thalamus using hybridization histochemistry. Maturation of CCK gene expression occurred over the course of a month, beginning in the medial geniculate nucleus on the 17th day of gestation. CCK mRNA was found in the caudal nuclei first, later in the rostral; the ventral were followed by the dorsal; and the lateral by the medial. In some nuclei, such as the medial geniculate, CCK mRNA was present prior to the full differentiation of the neurons; whereas in others, such as the mediodorsal, the neurons differentiated to almost adult morphology before CCK mRNA was detected.     

Effects of frontal cortex lesions on action sequence learning in the rat

To understand the role of frontal cortex in motor sequence learning we compared the effects of motor (M1), premotor (M2) and midline frontal (MFr) cortical lesions on rats making nose-pokes guided by luminance cues. Organizational demands were manipulated by varying the number (1 vs. 5) and predictability (random vs. repeated) of nose-pokes in a response. Learning was studied by comparing sessions with random or repeated cues. All cortical lesions increased reaction time (RT) during response initiation. These effects were larger for nose-pokes initiating sequential responses but spared RT for nose-pokes completing them. Repetition learning had significant effects on the speed and accuracy of single nose-poke responses that were unaffected by any of the cortical lesions. Repetition learning had more complex effects on sequential responding. RTs increased for nose-pokes initiating sequences over several sessions of continuous repetition and then decreased or leveled off. RTs decreased incrementally across all repetition sessions for subsequent nose-pokes in repeated sequences, following a time-course consistent with habit learning. Lesions involving M2 and MFr cortex exacerbated the increase in RT during initiation without affecting the incremental decrease in RT for nose-pokes completing repeated sequences. These results were confirmed by analyses of interference effects when training shifted from repeated (learned) to random (novel) sequences or to a new repeated sequence. These results implicate dorsomedial frontal cortex in organizational aspects of sensory-guided responding and motor sequence learning reflected in RT during response initiation.     

伽玛刀对大鼠皮层神经元钠电流的影响

目的 观察伽玛刀对体外培养大鼠皮层神经元电压依赖性钠电流的影响.方法 将原代培养的神经元随机分为实验组和对照组,通过立体定向技术和18 mm准直器对实验组原代培养大鼠皮层神经元实施伽玛刀照射,中心剂量30 Gy.伽玛刀照射后1、3、7、10 d通过膜片钳技术在全细胞模式下记录实验组和对照组皮层神经元的电压依赖性钠电流,每组每时间点记录6～8个神经元.结果 实验组皮层神经元在伽玛刀照射后1、3、7、10 d时的电压依赖性钠电流峰值密度(pA/pF)分别为(89.94±4.65)、(84.13±4.56)、(80.27±5.18)和(80.80±5.41),与对照组神经元电压依赖性钠电流峰值密度[照射后1、3、7、10 d分别为(100.93±4.63)、(97.89±4.77)、(100.76±5.90)和(102.84±4.08)]相比,均显著减小(P＜0.05),且减小程度随观察时间延长而增加,呈一定时间依赖性.另外,实验组神经元电压依赖性钠电流的I-V曲线明显上移,下降支明显右移.结论 伽玛刀照射通过抑制电压依赖性钠离子通道的功能引起大鼠皮层神经元兴奋性下降,可能是伽玛刀照射抑制癫痫发作的分子机制之一.     

Frontal lobe dysfunction in unilateral lenticulostriate infarcts. Prominent role of cortical lesions.

Most studies on frontal lobe dysfunction (FLD) in patients with striatal lesions did not consider possible associated cortical lesions not seen on computed tomographic scans. To determine the possible role of such cortical lesions, we assessed FLD in 10 patients with unilateral lenticulostriate infarct on computed tomographic scans. Magnetic resonance imaging revealed an associated cortical infarct not seen on computed tomographic scans in four patients. Using a battery of neuropsychological tests sensitive to FLD, we found that (1) the crossed tapping test was the only FLD test significantly disturbed in patients with pure unilateral lenticulostriate infarcts, (2) FLD was only present in patients with associated cortical infarct, and (3) caudate lesions only account for the number of echopraxic errors in the crossed tapping test. We conclude that unilateral isolated lenticulostriate infarcts might not lead to FLD, even though they may disturb the development of strategies involved in motor procedural learning.