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Monkeys can associate visual stimuli with reward delayed by 1 s even after perirhinal cortex ablation, uncinate fascicle section or amygdalectomy.

In the present experiment monkeys learned concurrent associations of two-dimensional objects (presented on a computer screen) with delayed reward. Hypothetical mechanisms of associative memory, such as long-term potentiation (LTP), required coincidental activation of two population of neurons: one representing the object and the other signalling the reward. In monkeys neurons in area TE of temporal cortex show object-specific activity during object presentation but only fraction of those neurons remain active after stimulus offset. In a delayed reward condition the majority of object-specific neurons in TE cease firing before reward is given and can be detected. In the present study the rate of learning with 1000 ms delay of reward was no slower than learning with immediate reward. This indicates that information about the object is somehow retained across the delay, possibly somewhere outside TE. In the present study we tested that assumption. Area TE projects to the perirhinal cortex and, via uncinate fascicle, to the prefrontal cortex. In our hands, ablations of perirhinal cortex or disconnection of prefrontal cortex from TE (by transection of uncinate fascicle) did not impair learning with delayed reward. Ablation of amygdala, a structure involved in reward-learning, slowed down learning equally with and without delay. We conclude that retaining information about the visually perceived objects across a delay does not exclusively depend upon integrity of perirhinal cortex, or uncinate fascicle, or amygdala. Parallel involvement of those structures remains a possibility and establishment of the role of residual activity of TE neurons requires further neurophysiological investigation.

Amygdala↗

Columnar transformations in auditory cortex? A comparison to visual and somatosensory cortices.

Auditory cortical columns have been studied for decades, but intracolumnar processing in auditory cortex is still poorly understood, relative to what is known about such processing in visual cortex and somatosensory cortex. While there are certainly striking similarities in cortical structure across the modalities, investigations of auditory cortex anatomy and synaptic physiology have also found important differences from the columnar organization of other sensory cortices. In vitro and in vivo studies of thalamocortical transformations in the auditory system have begun to reveal the functional significance of these differences, and have defined the earliest stages of auditory cortical processing. However, the question of what transformations are performed within auditory cortical columns remains unresolved. Attempts to find laminar differences in auditory cortex, which could provide the key to understanding columnar transformations, have so far produced contradictory and inconclusive results. Direct analogies to primary visual and somatic sensory cortices would suggest that response properties such as bandwidth, inhibitory sideband structure, preferred modulation rate and modulation phase sensitivity might vary across layers in auditory cortex. While such analogies could prove useful as guidelines for future research, the best hope for understanding auditory columnar transformations may lie instead with a more modality-specific, functional approach.

Auditory Cortex↗

Androgen binding and metabolism in the cerebral cortex of the developing rhesus monkey.

The influence of gonadal steroids on the maturation of the cerebral cortex and their possible influence on cortical function are not well understood. The present study examines androgen binding and metabolism in regions of the cerebral cortex and several subcortical structures at different time points during the development of the rhesus monkey. Androgen binding and metabolism were assessed in selected cortical and subcortical regions from neonatal, juvenile, and adult rhesus monkeys. Specific high affinity androgen-binding sites (apparent equilibrium dissociation constants for [3H]R1881, 0.04-0.3 nM) were observed in many areas of the rhesus monkey brain. These areas included (but were not limited to) the hypothalamus, amygdala, dorsolateral prefrontal cortex, orbital prefrontal cortex, visual and somatosensory cortex, and corpus callosum. Although the highest level of androgen binding was observed in the hypothalamus (8-20 fmol/mg protein), cortical samples also had measurable levels of binding (1-5 fmol/mg protein). No apparent regional or developmental differences in the number or affinity of androgen-binding sites were detected in animals ranging from 1 week to 8 yr in age. Androgen metabolism via aromatization and 5 alpha-reduction was observed in all regions of the neocortex examined, although at lower levels than in the hypothalamus and amygdala. Overall production of estrogens and 5 alpha-reduced androgens declined approximately 10-fold from prenatal to early postnatal life in both cortical and subcortical structures. The presence of androgen binding and metabolism in the monkey cerebral cortex indicates that steroid hormones may have considerable impact on cortical function in primates at postnatal as well as prenatal ages.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Location of neurons giving rise to certain descending fiber systems in the sensomotor and orbitofrontal cortex].

By means of the horseradish peroxidase (HP) retrograde axonal transport method localization of HP-labelled neurons in the forebrain cortex making projections on some somatic (motor and sensory) spinal and truncal centers, as well as on the retucular formation, substantia nigra and hypothalamus has been studied. Certain peculiarities in localization of the neurons giving origin to various fibre systems in the forebrain cortex have been revealed. Differences are especially noticeable in the area of sulcus chiasmaticus. Only when HP is infected into the spinal cord there is nearly no labelled neurons in the orbital-frontal cortex, while if the enzyme is injected into other structures studied HP-positive cells are revealed in this cortical area. Numerous labelled neurons are noted in the orbital-frontal cortex when HP is injected into the reticular formation and nuclei of the midbrain--the red nucleus and substantia nigra. In the lateal sulcus area HP-positive neurons are revealed when the enzyme is injected into the spinal cord and substantia nigra. Neurons giving origin to the fibre systems running to the spinal cord and to a number of subcortical formations are situated in the layer V. Cortico-hypothalamic neurons, that localized not only in the layer V, but also in the layers III--IV of the frontal cortex and in the layer VI of the orbital cortex--in the presylvian fissure are, make the exception to the rule.

Animals↗

Motor control function of the prefrontal cortex.

The prefrontal granular cortex, with the premotor and motor areas, forms the frontal lobe. The three areas are allied by their proximity to one another and by their role in motor control. Of these three major subdivisions, the role of prefrontal cortex has been the most obscure. However, recent anatomical studies have elucidated the circuit basis for motor regulatory functions of the principal sulcus (Brodmann's area 9; Walker's area 46). In addition to well known and well worked out prominent connections with subcortical structures, e.g. the basal ganglia and deep layers of the superior colliculus, this area of prefrontal cortex is reciprocally connected to portions of the supplementary motor and premotor fields that are but one synapse removed from primary motor cortex. The principal sulcal cortex is additionally interconnected with the primary somatosensory area and the somatosensory association areas, in the frontoparietal operculum, with area PF of von Bonin and Bailey in the posterior parietal cortex, and with parts of the 'motor' thalamus. Recent behavioural and electrophysiological studies in monkeys (Macaca mulatta) demonstrate that the principal sulcus can influence delayed-responding, whether the response is a hand or an eye movement. The anatomical and functional evidence supports the thesis that prefrontal cortex has access to and can direct the output of several motor centres.

Animals↗

Thalamic connections with limbic cortex. I. Thalamocortical projections.

The thalamocortical projections to limbic cortex in the cat have been studied with retrograde and anterograde axonal transport techniques. Five limbic cortical areas were identified on the basis of cytoarchitecture. The five areas are the anterior limbic area, the cingular area, the dorsal and ventral retrosplenial areas, and the presubiculum. Each of these cortical areas received small injections of horseradish peroxidase, and the afferent thalamic nuclei were identified by retrograde labelling of cells. The cortical projection of each of the anterior thalamic nuclei and the lateral dorsal nucleus was determined autoradiographically. Each of the anterior thalamic nuclei and the lateral dorsal nucleus projects to limbic cortex by two pathways. One group of fibers leaves the rostral thalamus by the fornix, pierces the corpus callosum, joins the cingulate fasciculus to reach limbic cortex. The other group travels through the lateral thalamic peduncle and internal capsule. The anterior ventral nucleus projects primarily to the dorsal retrosplenial area, particularly to layer I, the deep portion of layer II, and superficial portion of layer III. Sparse projections also exist to the ventral retrosplenial area, the cingular area, and the presubiculum. Very sparse projections to the anterior limbic area are seen. The anterior dorsal nucleus projects primarily to the ventral retrosplenial area, particularly layers I, the deep portion of layer II, and superficial layer III. sparse projections exist to the dorsal retrosplenial area and presubiculum, but apparently no projections exist to the cingular or anterior limbic area. The anterior medial nucleus projects primarily to layers I and superficial III of the ventral retrosplenial area. sparse projections exist to each of the other limbic cortical areas. The lateral dorsal nucleus projects extensively onto limbic cortex. Prominent projections occur to layer I, the external granular layer and lamina dessicans of the presubiculum, layers I and III-IV of the dorsal retrosplenial area, and layers I, III, and IV of the cingular area. Sparse projections occur to the ventral retrosplenial area and the anterior limbic areas. Thalamocortical projections also originate in the midline and intralaminar nuclei including the central medial, reuniens, rhomboid, paracentral, central lateral, and central dorsal nuclei. These data indicate that the anterior thalamic nuclei project upon limbic cortex in a complex manner. Further, the projections to limbic cortex from the anterior nuclei overlap with projections from the lateral dorsal nucleus. This overlap of thalamic projections onto limbic cortex suggests a convergence of information from nonprimary sensory systems with information from the classical limbic system.

Animals↗

Transplantation of embryonic occipital cortex to the brain of newborn rats: a Golgi study of mature and developing transplants.

Segments of the occipital cortex were taken from rat embryos (E16-E19) and transplanted to the cerebral cortex or the tectal region of a newborn rat host. With the aid of Golgi impregnation techniques, neuron morphology was studied in cortical transplants which had survived for 1 week or more in the host brain. In mature transplants (greater than 4 weeks) three main groups of neurons, termed groups I-III, were identified. Group I neurons resembled pyramidal neurons of the intact cerebral cortex. No preferential orientation of either soma or dendrites of group I neurons was observed in the transplants, and some group I neurons had curved apical dendrites. Group II neurons had predominantly stellate form and their dendrites were densely covered with spines. Paucity or absence of dendritic spines characterized group III neurons which exhibited various dendritic topologies. Different neuron types were also recognized in immature transplants growing for 1 and 2 weeks in the host brain. The sequence of dendritic maturation of transplanted cortical neurons is similar to that seen in intact cortex, although the stage reached related more to the actual age of the transplant than to that of the host. Thus, group I neurons in the 1-week-old transplants taken from E16 embryos had not attained the same complexity of branching as pyramidal neurons in the surrounding host cortex, but rather resembled slightly younger cells more like those found in the cerebral cortex of the newborn rat. These results show, therefore, that at least the basic cell classes identified in intact visual cortex can also be recognized in the cortical transplants. This will provide a foundation for studies defining which cells project to the host brain and which are involved in particular intrinsic connections.

Animals↗

Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons.

The distribution of the afferents to the rat's prefrontal cortex originating in the thalamic mediodorsal nucleus and the amygdala was investigated with two fluorescent tracers. Special emphasis was laid on detecting the loci of neurons which project via axonal collaterals into both lateral and medial portions of the prefrontal cortex. It was found that a high number of neurons of the anterior portion of the basolateral amygdaloid nucleus terminate via collaterals in both the medial and lateral subfields of the prefrontal cortex. On the other hand, only a small number of mediodorsal thalamic cells were found to project to both sides of the prefrontal hemisphere via bifurcating axonal collaterals. These cells were situated exclusively in the lateral part of the medial segment of the mediodorsal nucleus. The majority of both thalamic and amygdaloid neurons with bifurcating axons originate from subregions whose cells innervate primarily the medial prefrontal cortex. In brain-stem, neurons of the nucleus raphé dorsalis also project via collaterals to the medial and lateral prefrontal regions. Furthermore, neurons of the dorsal and ventral premamillary nuclei, the lateral mamillary nucleus, the ventral tegmental area of Tsai, and the ventral tegmental nucleus of Gudden were found to project to the medial prefrontal cortex. Our results indicate a differential collateral organization of thalamic and amygdaloid afferents to prefrontal cortical fields. The anterior basolateral amygdala (which innervates via collaterals both the medial and lateral prefrontal subfields) may add a common input to either subfield, such as information on the significance of incoming stimuli to the animal's behavior, while the mediodorsal nucleus (whose segments are principally connected to only one prefrontal subfield) may add segment-specific information, for example, of a spatial-cognitive nature for the lateral segment and of an emotional nature for the central and medial segments. The existence of a basolateral limbic circuit, composed of the amygdala, the thalamic mediodorsal nucleus, and the prefrontal cortex, is confirmed and knowledge on its interconnectivity is extended. From an anatomical point of view these data provide arguments for both unitary and diverging functions of the prefrontal cortex.

Amygdala↗

Development of connections between the mediodorsal nucleus of the thalamus and the prefrontal cortex in the rat.

The postnatal ingrowth of thalamocortical fibers from the mediodorsal nucleus to the prefrontal cortex was investigated in relation to the development of cortical lamination. Like the dopaminergic fibers in the prefrontal cortex and the thalamic fibers in the visual cortex, the mediodorsal fibers have entered the prefrontal cortex at birth. Most of the fibers are found in the developing layer VI, but, in contrast to the above-mentioned systems, a considerable number of mediodorsal fibers have already penetrated into the upper, most immature part of the cortical plate on postnatal day 1. From day 1 to day 7 an increasing number of mediodorsal fibers reach the upper cortical plate, which by then is developing layer III, the terminal layer of these fibers. The reciprocal connection from the layer VI cells of the prefrontal cortex to the mediodorsal nucleus develops between day 4 and day 9. Finally, the projection from the contralateral prefrontal cortex to the mediodorsal nucleus is established around day 10. The early presence of the mediodorsal fibers in the upper, differentiating cortical plate might indicate an important role for the mediodorsal fibers in the laminar development of the prefrontal cortex.

Animals↗

Processing the spatial configuration of complex actions involves right posterior parietal cortex: An fMRI study with clinical implications.

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage.

Activities of Daily Living↗

Premotor cortex activation during observation and naming of familiar tools.

Positron emission tomography was used to investigate whether observation of real objects (tools of common use) activates premotor areas in the absence of any overt motor demand. Silent naming of the presented tools and silent naming of their use were also studied. Right-handed normal subjects were employed. Tool observation strongly activated the left dorsal premotor cortex. In contrast, silent tool naming activated Broca's area without additional activity in the dorsal premotor cortex. Silent tool-use naming, in addition to activating Broca's area, increased the activity in the left dorsal premotor cortex and recruited the left ventral premotor cortex and the left supplementary motor area. These data indicate that, even in the absence of any subsequent movement, the left premotor cortex processes objects that, like tools, have a motor valence. This dorsal premotor activation, which further augments when the subject names the tool use, should reflect the neural activity related to motor schemata for object use. The presence of an activation of both dorsal premotor cortex and ventral premotor cortex during tool-use naming suggests a role for these two areas in understanding object semantics.

Adult↗

Gravitropism of the primary root of maize: a complex pattern of differential cellular growth in the cortex independent of the microtubular cytoskeleton.

The spatio-temporal sequence of cellular growth within the post-mitotic inner and outer cortical tissue of the apex of the primary root of maize (Zea mays L.) was investigated during its orthogravitropic response. In the early phase (0-30 min) of the graviresponse there was a strong inhibition of cell lengthening in the outer cortex at the lower side of the root, whereas lengthening was only slightly impaired in the outer cortex at the upper side. Initially, inhibition of differential cell lengthening was less pronounced in the inner cortex indicating that tissue tensions which, in these circumstances, inevitably develop at the outer-inner cortex interface, might help to drive the onset of the root bending. At later stages of the graviresponse (60 min), when a root curvature had already developed, cells of the inner cortex then exhibited a prominent cell length differential between upper and lower sides, whereas the outer cortex cells had re-established similar lengths. Again, tissue tensions associated with the different patterns of cellular behaviour in the inner and outer cortex tissues, could be of relevance in terminating the root bending. The perception of gravity and the complex tissue-specific growth responses both proceeded normally in roots which were rendered devoid of microtubules by colchicine and oryzalin treatments. The lack of involvement of microtubules in the graviresponse was supported by several other lines of evidence. For instance, although taxol stabilized the cortical microtubules and prevented their re-orientation in post-mitotic cortical cells located at the lower side of gravistimulated roots, root bending developed normally. In contrast, when gravistimulated roots were physically prevented from bending, re-oriented arrays of cortical microtubules were seen in all post-mitotic cortical cells, irrespective of their position within the root.

Cell Size↗

Layer V pyramidal cells in the adult human cingulate cortex. A quantitative Golgi-study.

The anterior and posterior parts of the human cingulate cortex differ in their absolute number of neurons per unit volume, with fewer neurons in the anterior part. To test the hypothesis that lower absolute number and packing density of neurons in the anterior cingulate cortex are associated with an increased complexity in the neuropil compartment, dendritic arborizations of layer V neurons in both cingulate parts were analyzed in a Golgi study. Results show that these neurons in the anterior cingulate cortex have more primary and secondary basal dendrites than those in the posterior cingulate cortex. This establishes an association of a higher complexity of the dendritic arborization in the anterior cingulate cortex with a lower cell number per unit volume and larger neuropil compartment. The significant lower degree of dendritic arborization in the posterior cingulate cortex is accompanied by a higher cell packing density. These structural differences are associated with functional differences between the two parts of the human cingulate cortex.

Adult↗

Overflow of noradrenaline and dopamine in frontal cortex after [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (DSP-4) treatment: in vivo microdialysis study in anaesthetized rats.

The changes in the extracellular concentration of endogenous noradrenaline and dopamine in the frontal cortex following pretreatment with noradrenergic neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] were studied by in vivo microdialysis in rats anaesthetized with chloral hydrate. Noradrenaline and dopamine levels in frontal cortex were detected only when the uptake inhibitor, nomifensine (10 microM) was present in dialysis fluid. Under those conditions, the Na+ channel agonist veratridine and a depolarising concentration of potassium chloride (60 mM), applied locally through the microdialysis probe, increased the overflow of noradrenaline. Tetrodotoxin had an opposite effect. These results indicate that most of the noradrenaline probably arose from exocytotic release. Noradrenaline efflux in the frontal cortex of DSP-4 pretreated rats (52 +/- 6.1 fmol/sample) did not differ significantly from that of the control animals (69 +/- 4.9 fmol/sample). Dopamine efflux was not changed either (64 +/- 9.6 and 62 +/- 3.9 fmol/sample, respectively). The alpha 2-adrenoceptor antagonist, atipamezole (3 mg/kg i.p.), increased the overflow of noradrenaline in the frontal cortex of saline-treated rats by 100%, whereas in DSP-4 treated rats the increase was only around 30%. The overflow of dopamine was not changed under the conditions described. The effect of atipamezole in DSP-4 treated rats may be of smaller magnitude due to the diminished pool of releasable noradrenaline or due to a downregulation of presynaptic alpha 2-adrenoceptors in the frontal cortex. The perfusion of 60 mM KCl at the end of the experiment unexpectedly produced equivalent increases in noradrenaline and dopamine content in dialysates of both vehicle and DSP-4 treated rats. We conclude that the uptake inhibitor, nomifensine, and atipamezole, which had a stronger effect in vehicle-treated animals, reduced the effect of KCl-stimulation and masked the true difference in changes of noradrenaline efflux. Post-mortem tissue concentrations of noradrenaline 7 days after DSP-4 administration (50 mg/kg) were significantly reduced in the frontal cortex (54%), hippocampus (62.5%) and to lesser extent in the hypothalamus (27%) as compared to vehicle-treated rats. Dopamine and 3,4-dihydroxyphenylacetic acid concentrations were not changed confirming the efficacy and selectivity of the DSP-4 lesion. These results demonstrate that one week after DSP-4 treatment the extracellular levels of noradrenaline and dopamine as assessed by in vivo microdialysis are not changed in the frontal cortex, but atipamezole-stimulated release of noradrenaline is decreased in DSP-4 treated rats.

Adrenergic alpha-2 Receptor Antagonists↗

Transgeniculate signal transmission to middle suprasylvian cortex in intact cats and following early removal of areas 17 and 18: a morphological study.

Removal of cat areas 17 and 18 early, but not late, in postnatal development results in the sparing of certain reflexive and nonreflexive visually guided behaviors. These spared behaviors are accompanied by an expansion of geniculocortical projections to middle suprasylvian (MS) cortex. However, little is known about the types of visual signals relayed along these pathways. The purpose of our study was to reveal the morphologies of the neurons participating in the rewired circuits and, by relating them to the morphologies of functionally characterized neurons described by others, infer the types of visual signals transmitted via the lateral geniculate nucleus (LGN) to MS cortex. To do this, we retrogradely labeled LGN neurons from MS cortex with fluorescent microspheres, and subsequently intracellularly filled them with Lucifer Yellow. We then classified well-filled neurons according to a battery of morphological parameters (such as soma size and shape, and dendritic field-form and specializations), and compared them with already defined structure/function relationships. By doing this, we found that the large majority of visual thalamic relay neurons to MS cortex of both normal cats and cats that incurred removal of areas 17 and 18 were types I and IV. These results indicate that visual Y and W signals, respectively, are relayed directly from LGN to MS cortex in both types of cats. Following the early lesions, some of the MS-projecting type I neurons were found in layers A and A1, where they are never found in intact cats. Thus, some layer A and A1 type I neurons redirect axons to MS cortex following early removal of areas 17 and 18. For the type IV MS-projecting neurons in early lesioned cats, the somas were hypertrophied and they had more profuse and broader dendritic arbors than equivalent neurons in intact cats. These results suggest that dynamic interactions take place between inputs and outputs of LGN neurons during development that influence final LGN neuron morphology. Moreover, they suggest that signals transferred to MS cortex by type IV neurons may be modified by early lesions of areas 17 and 18. Overall, these results contribute to our understanding of the types of behaviors that may be spared by early lesions of areas 17 and 18.

Animals↗

Patterns of endogenous amino acid release from slices of rat and guinea-pig olfactory cortex.

A study has been made of the effects of depolarizing stimuli on the release of endogenous amino acid neurotransmitter candidates (aspartate, glutamate, GABA and taurine) from in vitro preparations of rat and guinea pig olfactory cortex. Exposure of small cubes of olfactory cortex tissue from either species to potassium chloride (50 mM) was accompanied by a calcium-dependent release of aspartate, glutamate and GABA. A similar release pattern was evoked by protoveratrine A (100 muM) although the release was largely calcium-independent. Neither agent led to increased release of taurine. Electrical stimulation of the excitatory input (lateral olfactory tract) of freshly prepared, synaptically intact olfactory cortex slices of both species induced significant release of aspartate and GABA from the uncut pial surface and of aspartate, GABA and glutamate from the cut surface. Evoked taurine release occurred from both surfaces of rat olfactory cortex slices but no release was detected from guinea pig olfactory cortex slices. These patterns of release were unaffected by changes in stimulus frequency and were mimicked by protoveratrine A (100 muM) applied to one or other surface. Preincubation of slices from rats for 2 led to loss of tissue amino acids and to changes in their release patterns; the presence of glutamine (5 mM) during preincubation prevented the loss of amino acids but did not alter their pattern of release. Because of the close similarities between both the electrophysiological properties and the patterns of amino acid release it is concluded that there is probably an identity of amino acid neurotransmitters (aspartate, glutamate and GABA) in rat and guinea pig olfactory cortex. The role of taurine in the rat olfactory cortex is unknown but would seem unlikely to be that of a neurotransmitter. The results are discussed: (i) in terms of the cellular origins of the released amino acids; and (ii) wit respect to apparent experimental discrepancies which have appeared in the literature.

Amino Acids↗

Glial DNA synthesis and cell proliferation in the lesioned frontal cortex of the rat.

Proliferation of rat neurological cells was quantified following a lesion of the frontal cortex, with the rate of incorporation of intraventricularly administered [3H]thymidine ([3H]TdR) into cortical DNA serving as an index of glial proliferation. Incorporation of [3H]uridine into the corresponding RNA fractions did not serve this purpose. The intraventricular route of administration of thymidine greatly reduced the amount of [3H]TdR needed to label DNA relative to systemic injection. The rate of incorporation of [3H]TdR into DNA was linear for 75 min post-injection. Significantly more [3H]TdR was incorporated into DNA of the lesioned frontal cortex than that of the contralateral control cortex, during the first 4 days post-trauma. The majority of the acid-insoluble radioactivity (from [3H]TdR) was localized in the nuclear subcellular fraction of the cortex. Experiments indicated that the enhanced incorporation of [3H]TdR was not the result of altered metabolism or pool sizes of TdR in the lesioned cortex. Histological analysis indicated that there was a significant increase in the number of glial cells in the lesioned cortex by day 4 post-lesion, which corresponded to the increase in DNA synthetic activity. It was concluded that mechanical trauma to the frontal cortex of the rat results in an increase in the number of glial cells at and near the lesion which is accompanied by an increase in incorporation of [3H]TdR into cortical DNA. This method of measuring posttraumatic DNA synthesis has several advantages over autoradiography.

Animals↗

Differential alterations of ion channel binding sites in temporal and occipital regions of the cerebral cortex in Alzheimer's disease.

Three ion channel binding sites were examined by means of quantitative ligand binding autoradiography in temporal and occipital cortex from 9 patients with neuropathologically confirmed Alzheimer's disease (AD) and 7 matched control subjects. The following ligands were used: 125I-apamin to label a population of Ca(2+)-sensitive K+ channels; [3H]PN200-110 to label L-type voltage-sensitive Ca2+ channels and [3H]glibenclamide to label ATP-sensitive K+ channels. Ion channel binding sites were compared to: choline acetyltransferase (ChAT) activity and plaque densities measured in the same tissue. In the temporal cortex in AD 125I-apamin binding was increased compared to controls (e.g. superficial layers: control = 0.71 +/- 0.07; AD = 1.02 +/- 0.07, mean +/- S.E.M. pmol/g tissue). In contrast, in adjacent sections [3H]glibenclamide binding was reduced in AD compared to controls (e.g. superficial layers: control = 25.3 +/- 1.7; AD = 17.9 +/- 1.4 pmol/g tissue). [3H]PN200-110 binding in temporal cortex was not altered in AD compared to controls. In the occipital cortex 125I-apamin binding was increased in AD while both [3H]glibenclamide and [3H]PN-200-110 binding sites in this cortical area were not different from controls. Plaque density (per mm2) was higher in temporal (e.g. layers I-III, 43 +/- 6) than in occipital cortex (layers I-III, 27 +/- 4) in the AD patients while ChAT activity was reduced by 40% in temporal cortex and by 50% in occipital cortex compared to controls. The results suggest that the three ion channel binding sites are located on structural elements in the brain which are differentially affected by the pathophysiology of AD.

Alzheimer Disease↗