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PubMed1983

Astrocytic development in fetal parietal cortex grafted to cerebral and cerebellar cortex of immature rats.

Pieces of cortex cerebri anlage were dissected out from 16- to 17-day-old fetuses and transplanted to the cortical and cerebellar regions of 5- to 6-day-old rat pups. Twelve animals with grafts in the cortical region and 5 animals with grafts in the cerebellar region were studied 1.5-4 months later. Cresyl violet stained sections revealed no gross difference in either cell morphology, cell density or cell distribution between grafts in the two locations. A molecular layer-like zone was present on all free surfaces of the grafts, whether facing a ventricle or the meninges. The astrocytic development was studied using immunohistochemistry with antibodies against glial fibrillary acidic protein, (GFA), and the S-100 protein. Both antibodies visualized starshaped astrocytes and perivascular membranes surrounding blood vessels. Semi-quantitative measurements as well as computerized image analysis showed that the total amount of GFA-like immunoreactivity was much higher in both types of grafts than in corresponding host cortex cerebri. No differences in amount of S-100-like immunoreactivity could be demonstrated. As S-100 is thought to be a more general astrocytic marker than GFA, this suggests that the difference in GFA-like immunoreactivity is due mainly to an increased amount of GFA within the individual astrocytes. It is concluded that grafts of fetal cortex cerebri pieces to the CNS of young hosts develop a profound astrocytic reaction characterized by an increased amount of GFA-like immunoreactivity.

Animals↗

PubMed1996

Memantine induces heat shock protein HSP70 in the posterior cingulate cortex, retrosplenial cortex and dentate gyrus of rat brain.

High-affinity N-methyl-D-aspartate (NMDA) receptor antagonists like MK-801 are known to induce the heat shock protein, HSP70, in the posterior cingulate cortex and retrosplenial cortex of rat brain. Memantine, which is a low affinity uncompetitive NMDA receptor antagonist, has been used in the treatment of Parkinson's disease in Europe. The faster kinetics of memantine in blocking and unblocking the NMDA receptor-operated ion channel as opposed to high-affinity NMDA antagonists like MK-801 has been thought to account for the safety of memantine. The present study evaluated the neurotoxic potential of memantine and amantadine using the induction of HSP70 immunoreactivity in rat brain. Memantine (25, 50, 75 mg/kg) induced HSP70 in the posterior cingulate, retrosplenial cortex and dentate gyrus of rat brain. In contrast, amantadine (50, 100, 200 mg/kg) did not induce HSP70 in the rat brain. These results suggest that memantine has an antagonistic effect at NMDA receptor in vivo, and raises the possibility that high doses of memantine may cause neuronal damage similar to those observed with other high-affinity NMDA receptor antagonists.

Animals↗

PubMed1997

Development of the striatal projection from embryonic neurons from the lateral or medial frontal cortex grafted homo- or heterotopically into the medial frontal cortex of newborn rats.

The present study was designed to further investigate the effects of intrinsic or extrinsic influences on the development of the efferent connectivity of frontal neocortical neurons. The lateral or medial parts of the frontal neocortex of embryonic (E) day 16 fetuses were grafted into homo- (medial-to-medial) or heterotopic (lateral-to-medial) position in the medial part of the left frontal cortex of newborn hosts. Three to four months after grafting, a retrograde neurotracer was injected into the dorsomedial or ventrolateral quadrant of the left caudate-putamen (CPU). The ensuing retrograde labeling in the transplants was then compared to that found in an equivalent cortical area in control animals. Medial-to-medial transplants developed a striatal projection whose mediolateral organization conforms to that of the projection arising from the medial part of the intact frontal cortex. The mediolateral distribution of the projection arising from lateral-to-medial transplants was not fundamentally different from that originating from medial-to-medial transplants, a finding which stands in marked contrast with what was found recently [7] with medial-to-lateral transplants. These results indicate that inside the frontal cortex, different subregions are not totally interchangeable, at least in terms of development of efferent connectivity.

Animals↗

PubMedDate not supplied

Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising relatively non-invasive alternative for the treatment of depression. The purpose of this study was to compare the apparent effectiveness of high frequency (20 Hertz) rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) with that of low frequency (1 Hz) rTMS applied over the right DLPFC METHODS: Twenty-eight antidepressant-free adults with major depressive (n = 25) or bipolar (n = 3) disorder (not on mood stabilizers) in a current major depression (Hamilton Rating Scale for Depression [HAM-D-21] > or = 18; Mean = 24.5, SD = 5.51) were treated (14 right, 14 left) for 4 weeks. RESULTS: Overall paired t-tests revealed a significant reduction in mean HAM-D-21, Beck Depression Inventory (BDI-II), and Clinical Global Impression of Change (CGIC) scores at the end of treatment for both groups (high frequency left DLPFC and low frequency right DLPFC). The treatment response rate found (32%) was typical of other response rates reported in the literature (6,30). One-month follow-up data was obtained from 50% of participants. At 1-month follow-up no significant differences were noted as compared to patients' performance at last treatment visit, indicating moderate robustness of rTMS treatment over time. Furthermore, magnetic stimulation did not substantially alter patient memory over the course of treatment. CONCLUSION: rTMS given at low frequency over the right frontal cortex appears to be as effective treatment of refractory depression as high frequency treatment over the left frontal cortex.

Antidepressive Agents↗

PubMed2004

Involvement of the superior temporal cortex and the occipital cortex in spatial hearing: evidence from repetitive transcranial magnetic stimulation.

The processing of auditory spatial information in cortical areas of the human brain outside of the primary auditory cortex remains poorly understood. Here we investigated the role of the superior temporal gyrus (STG) and the occipital cortex (OC) in spatial hearing using repetitive transcranial magnetic stimulation (rTMS). The right STG is known to be of crucial importance for visual spatial awareness, and has been suggested to be involved in auditory spatial perception. We found that rTMS of the right STG induced a systematic error in the perception of interaural time differences (a primary cue for sound localization in the azimuthal plane). This is in accordance with the recent view, based on both neurophysiological data obtained in monkeys and human neuroimaging studies, that information on sound location is processed within a dorsolateral "where" stream including the caudal STG. A similar, but opposite, auditory shift was obtained after rTMS of secondary visual areas of the right OC. Processing of auditory information in the OC has previously been shown to exist only in blind persons. Thus, the latter finding provides the first evidence of an involvement of the visual cortex in spatial hearing in sighted human subjects, and suggests a close interconnection of the neural representation of auditory and visual space. Because rTMS induced systematic shifts in auditory lateralization, but not a general deterioration, we propose that rTMS of STG or OC specifically affected neuronal circuits transforming auditory spatial coordinates in order to maintain alignment with vision.

Acoustic Stimulation↗

PubMed1982

Tridimensional study of the deep cortex of the rat lymph node. VI. The deep cortex units of the germ-free rat.

The deep cortex of the normal rat lymph node consists of semirounded lymphocytic structures, termed deep cortex "units," each being centered on the opening of an afferent lymphatic. The aim of the present work was to investigate the morphologic features of the units in germ-free animals, in an attempt to evaluate the influence on natural exogenous antigenic stimulation on the development of the units. For this, the lymph nodes from various anatomic locations from 8-week-old Sprague-Dawley germ-free rats were analysed tridimensionally. The observations revealed that, in comparison with the lymph nodes of normal rats, the units of the cervical and mesenteric lymph nodes of the germ-free animals were underdeveloped, while those of the brachial, inguinal, and popliteal lymph nodes were unchanged. Moreover, the germ-free state modified the units of the mesenteric lymph nodes in a manner not encountered in the remaining lymph nodes. Other morphologic features of the peripheral cortex of the lymph nodes of germ-free rats also differed from those of normal ones. The significance of these differences is discussed with respect to immune responses and the process of lymphocyte recirculation. They are of interest because they support previous proposals regarding some aspects of the functioning of the normal lymph node, accounting for the features of the structures and overall architecture of the organ.

Animals↗

PubMedDate not supplied

Prolonged postsynaptic changes in the sensorimotor cortex of the awake rabbit in response to stimulation of fibers of the white matter of the new cortex and the corpus callosum.

The postsynaptic changes in the focal potentials of the sensorimotor cortex of the awake rabbit was investigated in this study following tetanization of the corpus callosum and the white matter. Stimulation of these structures was carried out during testing. A prolonged (hour-long) increase in the amplitude of the responses was observed in some of the experiments following tetanization, as compared with the control prior tetanization. Just as long a decrease in the amplitude of the responses tested developed in a number of experiments in the posttetanic period. It was concluded that prolonged plastic changes can occur in different directions in the sensorimotor cortex of the awake rabbit.

Animals↗

PubMedDate not supplied

Specialization of motor cortex neurons in rabbits under normal conditions and after ablation of the visual cortex.

The activity of motor cortex neurons in instrumental food-acquisition behavior is compared in two control rabbits and in three rabbits after bilateral ablation of the visual cortex. Although the same types of neuron specialization were found in the experimental and control animals, their numerical ratio differed markedly in two out of the three experimental rabbits in comparison with the controls: the number of neurons activated in the act of seizing food was halved, while the number of neurons activated in connection with acts of instrumental behavior doubled. The similarity of the processes underlying behavior learning and recovery is discussed.

Animals↗

PubMedDate not supplied

Long-term changes in the efficiency of excitatory and inhibitory connections in neuronal micronetworks of the motor cortex induced by tetanization of the thalamic nuclei and the sensory cortex.

Tetanization of the ventrolateral nucleus of the thalamus, the red nucleus, and the sensory cortex produced long-term potentiation and depression of the efficiency of both excitatory and inhibitory connections in the neuronal micronetworks of the motor cortex in the cat. Rhythmic stimulation of various structures produced a variety of stable patterns of interneuronal connections in micronetworks. In monosynaptic excitation and disynaptic inhibition, the efficiency of inhibitory transmission was potentiated simultaneously with depression of the efficiency of excitatory transmission in the same post-synaptic cell. The efficiencies of synapses formed by axon collaterals of a given cell on its neighboring cells could change in different directions. These results may indicate that the sign (positive or negative) of modification may be determined by the activity of both cells, i.e., the pre- and post-synaptic cells.

Action Potentials↗

PubMed1983

Evidence for an amygdaloid projection to premotor cortex but not to motor cortex in the monkey.

Previous studies in the cat have demonstrated a direct projection from the amygdaloid complex to motor and premotor regions of the neocortex. In the present study both anterograde and retrograde tracer techniques have been used to determine whether a similar projection exists in the monkey brain. We have found that the dorsal, magnocellular division of the basal nucleus of the amygdaloid complex gives rise to a projection to the premotor cortex (Area 6), which terminates principally in layers I and II, and to a lesser extent in layer VI. No component of the amygdaloid complex has been found to project to the motor cortex (Area 4). The amygdaloid projection to Area 6 in the monkey appears to be substantially weaker than other rostrally directed projections from the basal amygdaloid nucleus to orbitofrontal and medial frontal areas, and also relatively weaker than the projection that has been described in the cat.

Afferent Pathways↗

PubMed1984

Reevaluation of motor cortex and of sensorimotor overlap in cerebral cortex of albino rats.

The organization of motor cortex and the sensorimotor overlap zone was examined by in-depth electrical stimulation using micromapping procedures in rats. The cutaneous somatic sensory, as well as the efferent motor projections to the hindlimb and forelimb sensorimotor overlap zone were studied in the same animals. Low-threshold movements were elicited from portions of 3 architectonic areas: the lateral agranular, dysgranular and granular areas. Cutaneous light touch projections occur only within the granular area. Cutaneous projections to, and motor projections from individual punctures in the granular overlap zone did not always involve homologous body parts. The total motor cortex exhibits a general musculotopic pattern of organization.

Animals↗

PubMed1988

Deviations in brain development of F2 generation on caloric undernutrition and scope of their prevention by rehabilitation: alterations in dendritic spine production and pruning of pyramidal neurons of lower laminae of motor cortex and visual cortex.

This is a report of comparison of developmental changes of spine densities on the different categories of dendrites of neocortical pyramidal neurons (V and VI layers of motor and visual areas) of Wistar rat, during 11-150 days of age, under conditions of normal nutrition and under chronic caloric but not protein deprivation. The studied animals were of F2 generation born to parents undernourished to a degree that their weights were only 40-50% of normal control. At such a level they would be active, reproduce, and not morbid. Similar level of undernutrition also continued in the F2 group studied. A group of undernourished animals was also, for rehabilitation, put on normal diet from 21 days of age. Visual and motor cortical area pieces were impregnated by Stensaas' rapid Golgi method. Spines were counted on successive 20-micron segments (I-IV) of both apical and basal dendritic main shafts as well as primary and secondary branches. The spine count per segment (density) in the normal population reached exuberant values by 26-50 days of age and later underwent a progressive decline or pruning by 30-50% or more by 150 days of age. The degrees of exuberance and pruning varied in different categories of dendrites, generally being more conspicuous in motor than visual cortex, and more in basal than apical dendrites. Under the conditions of chronic caloric restriction, the phenomenon of exuberance was retarded and pruning was not observed. On the contrary, there was a progressive increase in the spine densities on both basal and apical dendrites, in motor and visual cortex. By 150 days of age, the spine densities were not only greater than the final counts for respective segments in the normal animal, but even greater than the exuberant counts. Postweaning caloric rehabilitation had only a modest impact against this deviation. Preliminary data (intersections) of dendritic branching also indicated a similar pattern of changes (lag followed by increase), but of a lesser degree. These alterations in neuronal development are interpreted as biological adaptations evoked in shaping the homeostasis of the organism's brain and behaviour by factors of nurture.

Aging↗

PubMed1996

Synaptogenesis and dendritic growth in the cortex opposite unilateral sensorimotor cortex damage in adult rats: a quantitative electron microscopic examination.

Unilateral lesions of the forelimb area of the sensorimotor cortex in adult rats resulted in time-dependent increases in the number of synapses per neuron and the volume and membrane surface area of dendritic processes per neuron within layer V of the contralateral motor cortex in comparison to sham-operated rats. Based on previous findings of a behavioral relationship with increased dendritic arborization, these changes may be related to lesion-induced compensatory changes in the use of the non-impaired (ipsilateral to the lesion) forelimb.

Age Factors↗

PubMed1988

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats: reciprocal connections with host thalamus demonstrated with WGA-HRP.

Fetal frontal cortex was transplanted into lesion cavities formed in host motor/sensory cortex of adult rats. Eight to twenty-eight weeks later wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into host thalamus and the brain was sectioned and reacted using a sensitive TMB procedure. A large amount of fine granular WGA-HRP was detected in most transplants. This could represent anterograde transport demonstrating that injured adult host thalamic neurons sprouted axons into fetal cortical transplants. Conversely, none or very few retrogradely labeled pyramidal neurons were present in the transplants. This indicates that pyramidal neurons in transplants either did not sprout into adult host brain or sprouted such short distances that they did not pick up the WGA-HRP. These results are compatible with the hypothesis that high trophic/growth factor levels in newborn or fetal brain and low levels in adults determine the more extensive connections seen in newborn hosts compared with those in adult transplanted hosts. The data are also consistent with the proposal that adult host brains impair axonal growth. Functionally, the data suggest that although corticofugal effects of fetal cortical transplants in adult host brains are likely to be limited, transplants could exert beneficial trophic effects on adult host thalamic neurons.

Animals↗

PubMed1995

Expression of vimentin increases in the hippocampus and cerebral cortex after entorhinal cortex lesioning and in response to transforming growth factor beta 1.

Entorhinal cortex lesions (ECL) that damage the perforant path to the dentate gyrus of the hippocampal formation were used to model the regulation of vimentin (VIM) mRNA. ECL increased VIM mRNA in the ipsilateral hippocampus and in the ipsilateral cortex including the wound cavity within 1 day. By in situ hybridization, at 4 days post-ECL, VIM mRNA increased two-fold in the molecular layer of the dentate gyrus. VIM protein was co-localized by immunocytochemistry to astrocytes and microglia/macrophages. Transforming growth factor-beta 1 (TGF-beta 1), which was previously shown to increase in microglia/macrophages of the molecular layer after hippocampal deafferentation by ECL, was investigated as a regulator of VIM expression. Infusions of TGF-beta 1 into the lateral ventricle induced VIM mRNA with dose-dependence, e.g. infusion of 100 ng TGF-beta 1 increased VIM mRNA three-fold. The increase in VIM mRNA was localized by in situ hybridization to astrocytes and microglia in the molecular layer of the dentate gyrus. These findings further implicate TGF-beta 1 as a regulator of cytoskeletal proteins during synaptic reorganization.

Animals↗

PubMed2004

Cooperation of the anterior cingulate cortex and dorsolateral prefrontal cortex for attention shifting.

Attention shifting in the working memory system plays an important role in goal-oriented behavior, such as reading, reasoning, and driving, because it involves several cognitive processes. This study identified brain activity leading to individual differences in attention shifting for dual-task performance by using the group comparison approach. A large-scale pilot study was initially conducted to select suitable good and poor performers. The fMRI experiment consisted of a dual-task condition and two single-task conditions. Under the dual-task condition, participants verified the status of letters while concurrently retaining arrow orientations. The behavioral results indicated that accuracy in arrow recognition was better in the good performers than in the poor performers under the dual-task condition but not under the single-task condition. Dual-task performance showed a positive correlation with mean signal change in the right anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC). Structural equation modeling indicated that effective connectivity between the right ACC and right DLPFC was present in the good performers but not in the poor performers, although activations of the task-dependent posterior regions were modulated by the right ACC and right DLPFC. We conclude that individual differences in attention shifting heavily depend on the functional efficiency of the cingulo-prefrontal network.

Adult↗

PubMed2005

Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex.

Maintaining relevant information for later use is a critical aspect of working memory (WM). The lateral prefrontal cortex (PFC) and posterior sensory cortical areas appear to be important in supporting maintenance. However, the relative and unique contributions of these areas remain unclear. We have designed a WM paradigm with distraction to probe the contents of maintenance representations in these regions. During delayed recognition trials of faces, selective interference was evident behaviorally with face distraction leading to significantly worse performance than with scene distraction. Event-related fMRI of the human brain showed that maintenance activity in the lateral PFC, but not in visual association cortex (VAC), was selectively disrupted by face distraction. Additionally, the functional connectivity between the lateral PFC and the VAC was perturbed during these trials. We propose a hierarchical and distributed model of active maintenance in which the lateral PFC codes for abstracted mnemonic information, while sensory areas represent specific features of the memoranda. Furthermore, persistent coactivation between the PFC and sensory areas may be a mechanism by which information is actively maintained.

Adult↗

PubMed2003

Bilateral lesions of the insular cortex or of the prefrontal cortex block the association between taste and odor in the rat.

The neural basis for the association between taste and odor was investigated in the rat. First, behavioral procedures to study the mechanisms underlying the association between qualitative aspects of the odor and taste in rats were developed. Rats were presented with several pairings of the 0.3 mol/L NaCl solution and a flavor, and pairings of distilled water and another flavor. Then the rats received an IP injection of a furosemide to develop sodium deficiency. On the next day, the rats were presented with either of two types of odor-flavored water: water in which the flavor had been paired with NaCl, or water in which the flavor (grape or coffee) had been paired with distilled water. Normal rats avoided ingesting the water flavored with the odor previously paired with NaCl. Sodium-deprived rats, however, ingested the water flavored with that odor. Rats with lesions in either the insular cortex or in the prefrontal cortex neither preferred nor avoided the water flavored with the odor paired with NaCl. It was concluded that rats acquire association between taste and odor, and that the insular and the prefrontal cortices of the rats were involved in this association.

Animals↗