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Muscarinic receptor agonist-mediated modulation of neuronal activity in rat cerebral cortex.

Multiple cortical neuronal responses were elicited by the iontophoretic application of muscarinic receptor agonists and antagonists in the rat cerebral sensorimotor cortex in vivo. (1) The muscarinic receptor agonist, oxotremorine-M induced a biphasic effect on spontaneous firing. This was evident as an early brief increase in the firing rate over the spontaneous discharge followed by secondary inhibition of spontaneous activity. The excitation could be blocked by the muscarinic receptor non-selective antagonist atropine and by both the M1 receptor antagonist pirenzepine and the M2 receptor antagonists gallamine or methoctramine. Oxotremorine-M inhibition of spontaneous activity was not affected by the M1 receptor antagonist pirenzepine, while evaluation of its sensitivity to gallamine and methoctramine was not possible since these two M2 receptor antagonists also depressed spontaneous activity, unlike pirenzepine. Of the other two muscarinic receptor agonists, oxotremorine had inconsistent and weak excitatory effects whilst McN-A-343 had only weak excitatory or inhibitory effects on spontaneous activity. (2) Oxotremorine-M, oxotremorine and McN-A-343 had a depressant action on neuronal discharges evoked by glutamate or acetylcholine. A depressant effect of oxotremorine-M was also demonstrated on the early excitation evoked by subsequent applications of oxotremorine-M itself. Of the three muscarinic receptor agonists tested, oxotremorine-M was the most potent in evoking a long-term depression of evoked discharges, lasting from several minutes (greater than 5 min) to as long as 40 min. Oxotremorine-M-induced depression of evoked responses was most sensitive to the M2 receptor antagonists, whereas oxotremorine-induced depression was more sensitive to the M1 receptor antagonist pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Ultrastructure of synapses in cerebral cortex layer i in rats with low and high resistance to hypoxia.

Quantitative analysis of synapses in layer I of the sensorimotor cortex in rats with low resistance to hypoxia revealed pronounced changes in the number of synaptic vesicles docked at the presynaptic membrane in active synaptic zones under conditions of acute hypobaric hypoxia. In high-resistant animals the number of docked synaptic vesicles under these conditions remained unchanged. In was hypothesized that high sensitivity to hypoxia in low-resistant rats is determined by high reactivity of the synaptic transmission system.

Animals↗

Effects of intranigral substance P and neurokinin A injections on extracellular dopamine levels measured with microdialysis in the striatum and frontoparietal cortex of rats.

Extracellular levels of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the striatum and frontoparietal (sensorimotor) cortex in halothane-anesthetized rats were analyzed simultaneously using in vivo microdialysis. Basal DA levels, measured from the microdialysis perfusate, were 6.4 +/- 0.8 nM (n = 15) in the striatum and 0.9 +/- 0.1 nM (n = 15) in the frontoparietal cortex. Subcutaneous injections of d-amphetamine (2 mg/kg) increased DA levels 10-fold in the striatum and fivefold in the cortex. Injections of substance P (0.07 nmol/0.2 microliters) into the substantia nigra pars reticulata (SNR) increased DA and DOPAC levels approximately 30% in the ipsilateral striatum and approximately 50% in the ipsilateral frontoparietal cortex. Injections of neurokinin A (0.09 nmol/0.2 microliter) into the SNR increased DA and DOPAC levels approximately 30% in the ipsilateral striatum but did not significantly affect DA levels in the ipsilateral frontoparietal cortex, although DOPAC levels were increased by approximately 50%. It is suggested that striatal and cortical DA release is regulated differently by nigral substance P and neurokinin A terminals.

Animals↗

[The neuronal reactivity and interaction of the rat cerebral cortex during the microiontophoretic action of acetylcholine in a model negative learning situation].

Unit activity of 46 pairs of neurons of sensorimotor cortex of rats was studied in a model situation of habituation to repetitive microiontophoretic applications of acetylcholine (ACh). The difference between the types of reactions to ACh of two neighbouring neurons recorded by the same microelectrode was observed on 37% of cases. The difference between the dynamics of activity of neurons with similar patterns of reactions during repetitive action of stimuli was also shown. Stability of the excitatory connections between two neighbouring neurons under the conditions when one of them demonstrated the habituation to repetitive action of ACh were indicated by analysis of cross-correlation histograms.

Acetylcholine↗

[The functional-structural characteristics of the neurons in cultured explants of the cerebral cortex of rats subjected to immobilization-cold exposure in the prenatal developmental period].

A tissue culture was obtained from the sensorimotor cortex of rat embryos after keeping pregnant animals under immobilization-cold stress. The functional state of culture was determined by RNA synthesis intensity. On analysing the tissue morphology, much attention was paid to the pattern of cytoskeleton (microtubules and microfilaments) of neuronal processes. For both periods of cultivation (7 and 14 days), the levels of RNA synthesis in culture of stressed animals were weaker than in the control one by 44 and 34%, resp. After 2 weeks of incubation the density of microtubules, i.e. the number of microtubules per process width, was reduced by 26% in profiles of dendrites. No changes in the number of microfilaments were detected. Besides, destruction of the neuron cytoplasm, redistribution of microtubules within dendrites, and reduction in the number of synaptic endings were noticed. All these alterations seem to be caused by lowering the capability of neurons to form their processes.

Animals↗

Mood changes after surgery for tumors of the cerebral cortex.

OBJECTIVE: To identify cortical lesion sites associated with particular mood states. DESIGN: A prospective study of patients with tumors affecting the cerebral cortex. The patients were examined neuropsychologically 1 to 5 days preoperatively and 2 to 10 days, several months, and several years postoperatively. Only data from the preoperative and the first postoperative examination were considered in this report. SETTING: Neurosurgical department of the University of Heidelberg (Germany). PATIENTS AND SUBJECTS: A consecutive sample of 141 patients with brain tumors (84 female and 57 male) with cortical lesions caused by microsurgical tumor resection; 29 clinical control patients (having undergone surgery for slipped disks); and 18 normal control subjects. MAIN OUTCOME MEASURE: Preoperative and postoperative mood state as measured with an adjective checklist. RESULTS: (1) Patients with lesions of the ventral frontal cortex or lesions of the temporoparietal cortex reported postoperatively significantly (P < .01) worse mood states (anxiety/depression, irritability/anger, fatigue) than did patients in the other lesion and control groups. (2) A more detailed lesion analysis revealed that lesions of heteromodal frontal or parietal association cortexes, combined with paralimbic lesions, were responsible for the negative mood states. Lesions of the sensorimotor cortexes ameliorated the negative effects of heteromodal and paralimbic lesions. (3) Lesion laterality did not influence the mood states. CONCLUSIONS: Heteromodal cortexes may be especially concerned with emotionally relevant operations. A loss of these functions deprives limbic structures of one of their main sources of input and is therefore likely also to produce changes in feelings, that is, emotional states.

Adult↗

Neocortical grafting to newborn and adult rats: developmental, anatomical and functional aspects.

This report presents the results of neural transplantation experiments that were designed either to study neural developmental phenomena or to appraise the possible restorative capacity of grafts. The first part of the report deals with the findings of transplantation studies that were performed in newborn recipient rats in an attempt to determine the importance of extrinsic or intrinsic factors in the process of areal cortical differentiation. More precisely, we examined the extent to which extrinsic signals drive the pattern of efferent connections of neurons residing in different cortical areas. In the first experiment, we examined the general distribution pattern of efferents arising from homotopic as compared to heterotopic transplants of embryonic cortical tissue placed into the frontal cortex of newborn rats. Our findings indicated that embryonic occipital neurons transplanted heterotopically into the sensorimotor cortex: (a) only rarely contacted normal targets of the motor cortex, (b) systematically projected towards normal targets of the visual cortex, and (c) distributed fibers to structures normally receiving fibers from both the motor and visual cortex, either exclusively into the visual corticorecipient zone of the structure or into both the visual and motor corticorecipient zones. In the second experiment, we attempted to assess the densities of the spinal projections arising from homotopic or heterotopic transplants implanted into the frontal or occipital cortex of newborn rats. We provided evidence that transplants of embryonic neocortical neurons of frontal origin developed and maintained a spinal cord projection whatever their rostrocaudal position within the host neocortex, whereas transplants of occipital origin did not maintain a significant spinal cord projection in adulthood. Finally, in the third experiment, we analyzed the laminar and tangential distribution of the tectal projections developed by transplants of embryonic occipital cortex placed into the primary or secondary subdivisions of the occipital cortex of newborn rats. Abnormalities in the laminar and/or tangential organization of the tectal distribution of the transplant efferents were systematically found. Using these different transplantation paradigms, we provided increasing evidence that, in their heterotopic location, the embryonic neurons retain some of the developmental characteristics corresponding to their embryonic cortical site of origin. Our findings strongly suggested, therefore, that there is an early specification of neocortical neurons to develop area-specific efferents. In conclusion, converging lines of evidence suggest that regional differences in the neuroepithelium are predetermined early in development, thus leading to cerebral cortex parcellation, as hypothesized by Rakic (1988). In the second part of the report, we describe the results of a series of experiments dealing with the consequences of grafting embryonic cortex into the damaged cortex of adult rats. These effects were examined from an anatomical, metabolic, behavioral, and electrophysiological point of views. The experiments were conducted using either the frontal or the visual cortex as models to appraise the functional integration of the grafts into the motor or visual circuits, respectively. The first study was undertaken to examine the capacity of transplants of embryonic frontal neocortical tissue placed into the frontal cortex of an adult recipient to develop efferents into the host CNS. The results indicated that transplants of fetal neocortex placed into adult CNS had the capacity to develop efferents which seemed to grow over significant distances within the host corpus callosum but, in most cases, failed to penetrate deeply into the gray matter. The density of the efferent projections was, however, far weaker than that seen in newborn hosts. In the second study, the 2-deoxyglucose (2-DG) technique was used to examine the functional integration of hom

Age Factors↗

Abnormal function of the brain system supporting motivated attention in medicated patients with schizophrenia: an fMRI study.

BACKGROUND: Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals. METHOD: We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls. RESULTS: The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex. CONCLUSION: Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.

Acoustic Stimulation↗

Electroencephalogram during sleep in the cat: age effects on slow-wave activity.

In humans there is a substantial decline in NREM electroencephalographic (EEG) slow-wave activity with advancing age. The present findings show that similar age-related EEG changes occur in the cat. Slow-wave (0.5-4.0 Hz) EEG activity during NREM sleep was compared in six young adult (2-4 years) and six aged (10-12 years) cats of either sex. Computer measures of slow-wave incidence and amplitude disclosed significant age- and gender-related differences. Although old male and female animals were of comparable age, only males showed significant EEG alterations. These consisted of an attenuation of slow-wave amplitude over posterolateral cortex and reductions in both the incidence and amplitude of slow-wave activity over sensorimotor cortex.

Aging↗

Areas of the brain concerned with ventilatory load compensation in awake man.

There is broad agreement that the awake human ventilatory response to a moderate inspiratory load consists of a prolongation of inspiratory time (T(I)) with a maintenance of tidal volume (V(T)) and end-tidal P(C)(O(2)) (P(ET,C)(O(2))), the response being severely blunted in sleep. There is no agreement on the mechanisms underlying this ventilatory response. Six naive healthy males (aged 39-44) were studied supine with their heads in a positron emission tomography (PET) scanner to allow relative regional cerebral blood flow (rCBF) to be measured with H(2)(15)O given intravenously. A linearised resistive load (24 cmH(2)O (l s(-1))(-1)) could be added to the inspiratory limb of a breathing valve inserted into a tightly fitting facemask; inspiratory flow was measured with a pneumotachograph. The load was applied, without alerting the subject, when the radioactivity first reached the head. Six scans were performed with and without the load, in each subject. Relative rCBF contrasts between the loaded and unloaded breathing states showed significant activations in inferior parietal cortex, prefrontal cortex, midbrain, basal ganglia and multiple cerebellar sites. No activations were found in the primary sensorimotor cortex. The findings suggest that there is a pattern of motor behavioural response to the uncomfortable sensation that inspiration is impeded. This results in a prolongation of T(I), the maintenance of V(T) and a reduction in the degree of discomfort, presumably because of the reduction of mean negative pressure in the airways.

Adaptation, Physiological↗

Effects of L-glutamate on cyclic AMP levels in slices from different areas of rat cerebral cortex with a chronic iron-induced focus.

The effect of L-glutamate of cyclic AMP levels in different areas of rat cerebral cortex was examined during the development of an iron-induced focus in the left sensorimotor cortex. The addition of L-glutamate resulted in increased cyclic AMP levels in slices from the quarter of cortex with the iron-induced focus. The levels lowered in slices from the quarter of cortex most remote from the focus. Thus L-glutamate showed stimulatory and inhibitory effects on the accumulation of cyclic AMP.

Animals↗

Repetitive peripheral magnetic stimulation alleviates tactile extinction.

Despite its frequency in right brain damaged patients crucial mechanisms of tactile extinction are still obscure and treatments are unavailable. Recent PET observations suggest a hypometabolism in the primary and secondary somatosensory cortex of the lesioned hemisphere in patients with tactile extinction. Functional and morphological investigations have shown that the sensorimotor cortex has a remarkable capability of reorganization when the sensory inflow is changed. Repetitive peripheral magnetic stimulation (RPMS) applied in patients suffering from central paresis alleviates sensorimotor as well as cognitive deficits by the induction of proprioceptive inflow, thereby activating plasticity in the CNS. Based on the observation of reduced metabolic activity in patients suffering from tactile extinction we applied RPMS to explore the effects of peripheral sensory stimulation on tactile extinction. Fourteen right-hemisphere lesioned patients with tactile extinction were randomly allocated to an experimental and a control group. The experimental group received one single RPMS treatment of the left forearm as well as a condition of attentional cueing known to improve visual extinction. The control group, with comparable tactile extinction scores, neither received RPMS nor verbal cueing, but was tested twice to evaluate possible learning or test repetition effects. In the experimental group RPMS led to a significant reduction of left-sided extinctions in the recognition of different tactual surfaces, but had no effect on ipsilesional errors. In contrast, attentional cueing had no significant effect on left-sided extinction errors but unexpectedly increased right-hand extinction errors slightly but significantly. The control group showed stable extinction scores of the left- and right-hand stimulus across two measurements, thus ruling out learning or test repetition effects. These results show that sensory inflow is an important modulatory factor in tactile extinction. Furthermore, multiple RPMS may prove a promising way for the rehabilitation of patients with this disorder.

Adult↗

Muscarinic agonist-mediated induction of long-term potentiation in rat cerebral cortex.

A long-lasting potentiation (usually following an initial short depression) of neuronal evoked responses was induced in neurons of rat sensorimotor cortex after a single application of the muscarinic agonists, oxotremorine, McN-A-343, or oxotremorine-M. The potentiation was characterized as being of slow onset (several minutes), progressive development, long-lasting (for as long as two hours), and was evident for both glutamate- and acetylcholine-evoked neuronal discharges. Potentiation was manifested as an increase in the frequency and duration of the evoked neuronal discharges, in a dose-dependent fashion. Blockade could be achieved if a muscarinic antagonist (atropine, pirenzepine or gallamine) was applied prior to, but not after, development of the long-lasting potentiation. These results suggest that certain muscarinic agonists may be useful in reducing the memory deficits of patients with Alzheimer's disease.

Acetylcholine↗

Large, deep layer pyramid-pyramid single axon EPSPs in slices of rat motor cortex display paired pulse and frequency-dependent depression, mediated presynaptically and self-facilitation, mediated postsynaptically.

1. In slices of rat sensorimotor cortex, dual intracellular recordings were obtained from 1,952 pairs of deep layer pyramidal neurons. Where action potentials in one neurone elicited excitatory postsynaptic potentials (EPSPs, n = 56) in the other, responses to different presynaptic firing rates and patterns and at different postsynaptic membrane potentials were recorded and on some occasions both neurons were filled with biocytin. 2. Slices were fixed, sectioned again at 60 microns, and incubated with Avidin horseradish peroxidase (HRP), which was then visualized using the 3,3'-diaminobenzidine tetrahydrochloride (DAB) method. All neurones reported here that were identified histologically were pyramidal cells with their somata in the deep layers (V and VI). 3. One in 70 of the tests performed revealed a synaptic connection, 25 of which were studied in detail. Mean EPSP amplitude was 1.67 +/- 1.66 (SD) mV, with some single sweep events as large as 9 mV. For some of the smaller EPSPs the amplitude distributions contained a clear peak around 0 mV, the coefficient of variation (CV) was large, and paired pulse facilitation was apparent. EPSPs with large average amplitudes displayed no apparent failures of transmission, EPSP amplitudes were fairly evenly distributed around the mean, CVs were small, and paired pulse depression was apparent in 2.5 mM extracellular Ca2+. When single sweeps were selected according to the size of the first EPSP, large second EPSPs were found to follow small first EPSPs and small second EPSPs to follow large first EPSPs. Paired pulse effects appeared, in the majority of tests, to be due to a change in presynaptic release probability. 4. Two EPSPs were recorded in three different extracellular Ca2+ concentrations. In 1 mM Ca2+, the first EPSP of a short interval pair was small and paired pulse facilitation was apparent. In 5 mM Ca2+, first EPSPs were between 2.5 and 4 times larger than in 1 mM Ca2+ and paired pulse depression was apparent. In all Ca2+ concentrations however, averaged third and fourth EPSPs of brief bursts were of similar amplitudes and smaller than second EPSPs. If presynaptic inhibition does contribute to paired pulse effects here, it is not overcome by a combination of raised extracellular Ca2+ and repetitive presynaptic firing. 5. These EPSPs displayed a wide range of time courses. The mean 10-90% rise time was 2.49 +/- 1.08 ms, the mean width at half amplitude was 15.39 +/- 5.42 ms (n = 22), and the mean EPSP latency was 1.59 +/- 0.68 ms (n = 18). (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Regional difference in depolarization-elicited accumulation of cyclic AMP in cobalt-induced epileptic cortex of the rat.

The appearance of epileptiform discharges in electrocorticograms was induced by a unilateral injection of CoCl2 solution into the sensorimotor cortex of rats. Accumulation of cyclic AMP elicited by ouabain or a high concentration of potassium ions was determined in slices from different cortical areas of rats 9 or 10 days after the injection. In the anterior cortex, the depolarization-elicited accumulation of cyclic AMP was significantly higher in the cortical area ipsilateral to the injection site than in the contralateral cortical area. In the posterior cortex, a similar but not significant difference in the accumulation of cyclic AMP was noted.

Animals↗

[Synaptic reactions of sensomotor cortex neurons to stimulation of emotionally significant brain structures].

The study deals with synaptic and spike responses of neurones in the rat sensorimotor cortex to stimulation of the lateral and medial hypothalamus, locus coeruleus and raphe nuclei. The activity of 57 neurones was recorded, 41 of them intracellularly and quasi-intracellularly, in response to the stimulation of sites in these structures, which were previously identified as "emotionally/ significant. No considerable differences in the effects of the stimulation of different "emotiogenic" zones were found. The stimulation parameters, differing from the "behavioural" ones by a greater strength, elicited in the majority of neurones clear post-synaptic responses, often in the form of EPSP-IPSP. Latencies of the responses varied from 3 to 80 msec. The most stable and pronounced responses were obtained to the stimulation of the lateral hypothalamus. No significant correlations of the latencies of the responses to the stimulation of different "emotiogenic" structures were found.

Animals↗

[Spike responses of sensomotor cortex neurons to isolated and combined stimulation of thalamic nuclei].

Simultaneous records of spike activity of several neighbouring neurones in the cat sensorimotor cortex have shown that isolated single stimulations of the thalamic ventroposterolateral nucleus (VPL) produce in different units of one and the same cortical microarea impulse responses visibly differing by their latencies and general pattern of discharges. These initially different reactions underwent pronounced changes under the action of combined stimulation of the VPL and the ventrolateral thalamic nucleus (VL). Ordinarily such changes were oppositely directed: enhancement of reactions of certain neurones was developing parallel with diminished activity of others of the same cortical microarea.

Animals↗

Electrophysiological analysis of motor cortical plasticity after cortical lesions in newborn rats.

Intracortical microstimulation of the motor cortex in normal adult rats evoked low threshold contralateral forelimb movements and high threshold ipsilateral movements. Ablation of the opposite sensorimotor cortex in adult animals did not alter these thresholds. However, stimulation of the unablated hemisphere in adult rats that sustained unilateral sensorimotor cortical lesions as neonates elicited low threshold ipsilateral forelimb movements that were similar to contralateral movements. These low threshold ipsilateral movements may be mediated via aberrant corticofugal pathways which are known to develop following neonatal cortical lesions.

Animals↗