Zinc-positive afferents to the rat septum originate from distinct subpopulations of zinc-containing neurons in the hippocampal areas and layers

The purpose of the present study was to examine whether zinc-positive and zinc-negative hippocampal neurons in rats differed with respect to their projections to the septum. By combining retrograde axonal transport of the fluorescent tracer Fluoro-Gold with histochemical demonstration of zinc selenide complexes in zinc-containing neurons after intraperitoneal injection of sodium selenite, we were able to visualize the distribution of retrogradely Fluoro-Gold labeled neurons and zinc-containing neurons in the same sections. After unilateral injection of Fluoro-Gold into the rat septum a few retrogradely labeled cells were observed in layer IV of the ipsilateral medial entorhinal area, and numerous labeled cells were observed mainly in the superficial layers of the ipsilateral subicular areas and throughout the CA1 and CA3 pyramidal cell layers, as well as in the contralateral CA3 pyramidal cell layer. Zinc-containing neurons were observed in layers IV–VI of the medial entorhinal area, layers II and III of the parasubiculum, layers II, III and V of presubiculum, and in the superficial CA1 and deep CA3 pyramidal cell layers. Cells double-labeled with Fluoro-Gold and zinc selenide complexes were primarily located in distal (relative to the area dentata) parts of the superficial CA1 pyramidal cell layer and distal parts of the deep CA3 pyramidal cell layer and in layers II and III of presubiculum. Only a very few double-labeled cells were seen in the contralateral CA3. The result demonstrates that the hippocampo-septal projection of rats is a mixture of zinc-positive and zinc-negative fibers. Where-as zinc-negative fibers originate from neurons throughout the hippocampal and retrohippocampal areas, zinc-positive fibers originate from distinct subgroups of zinc-containing cells in different areas and layers.     

The mode of synaptic activation of pyramidal neurons in the cat primary somatosensory cortex: an intracellular HRP study

Summary A total of 141 pyramidal neurons in the cat primary somatosensory cortex (SI) were recorded intracellularly under Nembutal anesthesia (7 in layer II, 43 in layer III, 8 in layer IV, 58 in layer V and 25 in layer VI). Most neurons were identified by intracellular staining with HRP, though some layer V pyramidal neurons were identified only electrophysiologically with antidromic activation of medullary pyramid (PT) or pontine nuclear (PN) stimulation. Excitatory synaptic potentials (EPSPs) were analyzed with stimulation of the superficial radial nerve (SR), the ventral posterolateral nucleus (VPL) in the thalamus and the thalamic radiation (WM). The pyramidal neurons in layers III and IV received EPSPs at the shortest latency: 9.1±2.1 ms (Mean+S.D.) for SR and 1.6±0.7 ms for VPL stimulation. Layer II pyramidal neurons also responded at a short latency to VPL stimulation (1.7±0.5 ms), though their mean latencies for SR-induced EPSPs were relatively longer (10.6±1.9 ms). The mean latencies were much longer in layers V and VI pyramidal neurons (10.2±2.4 ms and 2.9±1.5 ms in layer V pyramidal neurons and 9.9±2.5 ms and 2.8±1.6 ms in layer VI pyramidal ones, respectively for SR and VPL stimulation). The comparison of the latencies between VPL and WM stimulation indicates that most layer III–IV pyramidal neurons and some pyramidal cells in layers II, V and VI received monosynaptic inputs from VPL. These findings are consistent with morphological data on the laminar distribution of thalamocortical fibers, i.e., thalamocortical fibers terminate mainly in the deeper part of layers III and IV with some collaterals in layers V, VI and II-I. The time-sequences of the latencies of VPL-EPSPs indicate that corticocortical and/or transcallosal neurons (pyramidal neurons in layers II and III) fire first and are followed by firing of the output neurons projecting to the subcortical structures (pyramidal neurons in layers V and VI).     

Changes in the axonal conduction velocity of pyramidal tract neurons in the aged cat.

The present study was undertaken to determine whether age-dependent changes in axonal conduction velocity occur in pyramidal tract neurons. A total of 260 and 254 pyramidal tract neurons were recorded extracellularly in the motor cortex of adult control and aged cats, respectively. These cells were activated antidromically by electrical stimulation of the medullary pyramidal tract. Fast- and slow-conducting neurons were identified according to their axonal conduction velocity in both control and aged cats. While 51% of pyramidal tract neurons recorded in the control cats were fast conducting (conduction velocity greater than 20 m/s), only 26% of pyramidal tract neurons in the aged cats were fast conducting. There was a 43% decrease in the median conduction velocity for the entire population of pyramidal tract neurons in aged cats when compared with that of pyramidal tract neurons in the control cats (P < 0.001, Mann-Whitney U-test). A linear relationship between the spike duration of pyramidal tract neurons and their antidromic latency was present in both control and aged cats. However, the regression slope was significantly reduced in aged cats. This reduction was due to the appearance of a group of pyramidal tract neurons with relatively shorter spike durations but slower axonal conduction velocities in the aged cat. Sample intracellular data confirmed the above results. These observations form the basis for the following conclusions: (i) there is a decrease in median conduction velocity of pyramidal tract neurons in aged cats; (ii) the reduction in the axonal conduction velocity of pyramidal tract neurons in aged cats is due, in part, to fibers that previously belonged to the fast-conducting group and now conduct at slower velocity.     

Pattern of pyramidal tract collateralization to medial thalamus,lateral hypothalamus and red nucleus in the cat

Summary Stimulating electrodes were placed in the red nucleus, lateral hypothalamus and medial thalamus in order to determine whether pyramidal tract (PT) neurons send collaterals to those sites. The red nucleus projections are well-known, but it was discovered that PT neurons also project into the other two sites. All of the fibers that sent collaterals to all three sites originated from fast PT neurons. Those that responded to stimulation of the skin and that sent collaterals to two or three sites were predominantly fast PT neurons. Those neurons that responded only to cerebral peduncle stimulation were predominantly slowly-conducting, when compared with the set of PT neurons in response to cerebral peduncle stimulation. The patterns of collateral branching to red nucleus and to lateral hypothalamus were similar, suggestimg a similar synaptic effect of the pyramidal system in the two sites. Measurement of the speed of conduction from three sites along the length of corticospinal fibers revealed large changes on some, but not all, fibers; there was no evident pattern to these changes that might be associated with collateral branching. A new hypothesis concerning the functional role of fast PT neurons in regulating movement is presented.Dr. Canedo was supported by a Fogarty International Research Fellowship     

Commissural afferents innervate glutamate decarboxylase immunoreactive non-pyramidal neurons in the guinea pig hippocampus

The innervation of GABAergic hippocampal neurons by commissural fibers was investigated in the guinea pig by a combined anterograde degeneration - immunocytochemical technique. Presumed GABAergic neurons were identified by immunocytochemistry for glutamate decarboxylase (GAD) and the commissural fibers by electron-dense degeneration following contralateral transection of the fimbria. Commissural afferents were found to establish asymmetric synaptic contacts with non-pyramidal GAD-immunoreactive neurons located in subpyramidal and suprapyramidal zones of region CA1. The observed connection suggests that inhibition of pyramidal cells may occur in a feed-forward manner as postulated by electrophysiological studies.     

Electrophysiological evidence using focal flash photolysis of caged glutamate that CA1 pyramidal cells receive excitatory synaptic input from the subiculum

The hippocampus sends efferent fibers to the subiculum, which projects to the entorinal cortex. Previous studies suggest that the hippocampal CA1 area may receive a projection back from the subiculum. This hypothesis was tested using whole cell recording from CA1 pyramidal cells while subicular neurons were selectively stimulated with focal flash photolysis of caged glutamate, which avoids stimulation of fibers of passage. Control experiments showed that focal flash stimulations caused direct glutamate-mediated depolarizations and bursts of action potentials in the recorded CA1 pyramidal cells, but only when the stimulation targeted the somatodendritic regions of a neuron, not the axons. To block GABA(A)-mediated inhibition and isolate local excitatory circuits, bicuculline was applied to minislices containing only the isolated CA1 area and the subiculum. Of 24 CA1 pyramidal cells, 25% (6 of 24) consistently generated repetitive excitatory postsynaptic currents (EPSCs) in response to flash stimulation in the subiculum. The responsive neurons were located 200-500 microm from the distal end of CA1 and 400-1,100 microm from the stimulation sites in subiculum, suggesting excitatory synaptic projections from the subicular neurons to CA1 pyramidal cells. This study provides new electrophysiological evidence that CA1 pyramidal cells receive excitatory synaptic input from the subiculum. Thus a reciprocal excitatory synaptic circuit connects the subiculum and the CA1 area in the normal adult rat.     

Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis domestica). A Golgi study

Summary The neocortex of the cat undergoes a series of fundamental transformations of its fibrillar-neuronal organization during the course of early prenatal cortical ontogenesis. Some of these transformations assume structural chracteristics and neuronal features which resemble those of phylogenetically older cortical organizations. Following the arrival of corticipetal fibers at the marginal zone of the cerebral vesicle a very primitive neocortical organization, the primordial plexiform layer develops. It is characterized by the external location of the white matter with both corticipetal and a few corticofugal fibers and a few immature neurons sandwiched between the fibers. The primitive plexiform layer is present in the cat from the 20th to the 25th day of gestation. The external (superficial) location of the white matter of the primordial plexiform layer of the cat neocortex is reminiscent of the amphibian cortical organization. It also resembles other primitive structures (spinal cord) of the central nervous system. In view of its short duration and because of the immaturity of its fibrillar-neuronal elements, the primordial plexiform layer is considered to be a transient neocortical organization possibly without functional activity in the cat.The appearance of the cortical plate (25th day of gestation) causes the subdivision of the primordial plexiform layer into an outer and an inner zone. The outer zone becomes layer I and the inner zone layer VI of the neocortex. Both of these layers remain as such throughout cortical development. From the 25th to the 45th day of gestation the fibrillarneuronal structure of layers I and VI develop while the cortical plate grows, passively, by the progressive addition of new cells. The progressive fibrillar-neuronal organization of layers I and VI and the development of structural and functional interactions between them constitutes the primordial neocortical organization of the cerebral cortex of the cat. It is characterized by a superficial (layer I) and a deep (layer VI) plexiform layer composed predominantly of collaterals from the corticipetal fibers arriving at the developing cortex and by three basic types of neurons. The horizontal neurons of layer I with descending axons terminating in layer VI, and the Martinotti neurons of layer VI with ascending axons terminating in layer I, are associative neurons. The large stellate neurons of layer VI are projective neurons. The axons of these cells before entering the white matter send ascending recurrent collaterals to layer I. The fibrillar-neuronal organization of the neocortex during this gestational period (primordial neocortical organization) resembles the organization of the reptilian neocortex. It is postulated that the primordial neocortical organization of the cat is functionally active during this gestational period.The arrival of new types of afferent fibers at the lower region of the cortical plate (45th day of gestation) causes the maturation of the pyramidal neurons of this region of the neocortex. These neurons are recognized at this age as the pyramidal neurons of layer V of the neocortex of the cat. The appearance of these afferent fibers and the maturation of the pyramidal neurons of layer V marks the transformation of the neocortex from its primitive reptilian structure into a distinctly mammalian organization. It is postulated that the cortical plate (pyramidal plate) is a recent addition in neocortical phylogeny representing a mammalian transformation. An analogy seems to exists among the pyramid-like neurons of the amphibian cortex, the pyramid-like neurons of the reptilian neocortex and the pyramid-like neurons (stellate) of layer VI of the mammalian neocortex. This analogy differs from the classical one postulated by Cajal which includes the pyramidal neurons of the mammalian neocortex, which are here considered as recent additions to neocortical phylogeny and hence as distinct mammalian neurons.Supported by Grant HD-03298-09, and by General Research Support Grant FR-05392 from the General Research Branch, National Institutes of Health.     

Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na(+) channel-mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na(+)-to-K(+) conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.     

Branching cortical neurons in cat which project to the colliculi and to the pons: a retrograde fluorescent double-labeling study

Summary The fluorescent double-labeling technique has been used to determine whether the corticopontine and the corticotectal fibers in the cat are derived from two different sets of neurons or whether they are derived from branching neurons which distribute collaterals to the pontine grey and the colliculi. After unilateral DY.2HCl injections in the pontine grey and FB injections in the ipsilateral colliculi, large numbers of FB-DY.2HCl double-labeled neurons were present in the cortex of the ipsilateral hemisphere. However, the labeled neurons in its rostral part may have represented pyramidal tract neurons which were labeled retrogradely because their fibers descended through the DY.2HCl injection area. Therefore, also DY.2HCl injections were made in the pyramid (i.e. caudal to the pons) and the cortical pyramidal tract area, containing the retrograde DY.2HCl-labeled neurons, was delineated. In the rest of the experiments only the DY.2HCl-labeled neurons in the caudal two thirds of the hemisphere (outside the pyramidal tract area) were taken into account because only these neurons could, with confidence, be regarded as corticopontine neurons. In some anterograde HRP transport experiments the trajectories of the corticotectal and the corticopontine fibers were visualized. On the basis of the findings the DY.2HCl injections in the pontine grey were placed such that they could not involve any of the corticotectal fibers passing from the cerebral peduncle to the colliculi. Thus artifactual doublelabeling of cortical neurons was avoided. However, also under these circumstances many double-labeled neurons were present in the caudal two thirds of the hemisphere. This led to the conclusion that in the cat a large proportion of the corticopontine neurons in the caudal two thirds of the hemisphere represent branching neurons which also distribute collaterals to the colliculi. The parietal (anterior part of the lateral gyrus, middle and posterior suprasylvian gyri) and the cingulate areas together contained three quarters of all labeled corticopontine neurons outside the pyramidal tract area. In the parietal areas roughly 25% of them were double-labeled and in the cingulate area 14%. However, in the visual areas 18 and 19 a much larger percentage (30–60%) was doublelabeled. In a recent study from our laboratory it was found that in the cat the pyramidal tract fibers distribute an abundance of collaterals to the pontine grey. Therefore, a large proportion of all corticopontine connections in this species appear to be established by branching neurons which also distribute fibers to other cell groups in the brain stem and the spinal cord.Abbreviations A.E. anterior ectosylvian sulcus - a.e.s. anterior ectosylvian sulcus - BC brachium conjunctivum - BCI brachium colliculus inferior - BP brachium pontis - cor. sulc. coronal sulcus - CP cerebral peduncle - CR. cruciate sulcus - CUN cuneiform nucleus - DBC decussation brachium conjunctivum - DLP dorsolateral pontine nucleus - IC inferior colliculus - inf. coll. inferior colliculus - INS. insula cortex - IO inferior olive - IP interpeduncular nucleus - LAT. lateral sulcus - l.s. lateral sulcus - MG medial geniculate body - LL lateral lemniscus - ML medial lemniscus - MLF medial longitudinal fascicle - NdG dorsal nucleus of Gudden - NLL nucleus lateral lemniscus - NRTP reticular tegmental pontine nucleus - ORB. orbital sulcus - P pyramid - PAG periaqueductal grey - P.E. posterior ectosylvian sulcus - RF reticular formation - PG pontine grey - RB restiform body - RN red nucleus - S. sylvian sulcus - SC superior colliculus - SN substantia nigra - SO superior olive - SPV spinal trigeminal complex - S.S. suprasylvian sulcus - s.syl.s. suprasylvian sulcus - S.SPL. suprasplenial sulcus - SPL. splenial sulcus - spl.s. splenial sulcus - sup. coll. superior colliculus - syl.s. sylvian sulcus - TB trapezoid body - VC vestibular complex - Vm trigeminal motor nucleus - Vs trigeminal principle nucleus - III oculomotor nucleus - IV trochlear nucleus - VI abducens nucleus - VII facial nerve - VIII vestibulo-trochlear nerve Supported in part by grant 13-46-91 of FUNGO/ZWO (Dutch Organization for Fundamental Research in Medicine)     

Pericruciate cortical neurons projecting to brain stem reticular formation,dorsal column nuclei and spinal cord in the cat

Cells of origin of the pericruciate cortical fibers to the bulbar medial reticular formation, the dorsal column nuclei and the pinal cord in the cat were identified by means of the retrograde axonal transport of horseradish peroxidase. After injection of the enzyme in the dorsal column nuclei or the spinal cord many layer V pyramidal neurons were labeled retrogradely in areas 2, 3 and 4 (see ref. 6), but area 4 giant Betz cells were only labeled after spinal cord injections. Medial bulbar reticular formation injections resulted in the labeling of pyramidal neurons mainly in area 6.     

Pyramidal control of skin potential responses in the cat

Summary Pyramidal command of Skin Potential Response (SPR) was investigated in 20 cats paralyzed by gallamine and under a halothane anaesthetic. For each animal, a transection of the medulla sparing only the pyramidal tract was carried out. The pyramidal tract and Mesencephalic Reticular Formation (MRF) were stimulated before and after the transection. Results taken before transection show that the SPR can be elicited from stimulation of the pyramidal tract and the MRF. After transection, stereotaxic stimulations of the pyramidal tract still evoked the SPR even after aspiration of the medullary tissue posterior to the section and overlying the pyramids. Control reticular stimulations with higher stimulus intensities failed to evoke the SPR. These results show that stimulation of the pyramidal tract can elicit the SPR independently of reticulospinal neurons. It is hypothesized that a group of corticospinal fibers could transmit volleys having autonomic activity on preganglionic autonomic neurons of the intermediate zone of the grey matter.A.H. Sequeira-Martinho is a research fellow of the Instituto Nacional de Investigaçao Cientifica (INIC), Lisboa, Portugal     

NADPH diaphorase histochemistry of the human hypothalamus

The morphology and distribution of NADPH diaphorase reactive neurons was studied in the normal human hypothalamus. Reactive neurons were divided into three categories on the basis of perikaryal size. Small neurons (8–20 μm) were oval or fusiform, and pale staining. Intermediate neurons (20–30 μm) were fusiform, triangular or pyramidal with a wide range of staining intensity. Large neurons (> 30 μm) were triangular or pyramidal with moderate to dark staining. Reactive neurons were found in four major regions: medial preoptic, ventromedial, lateral, and perifornical. Scattered positive neurons were found in several other hypothalamic areas. Reactive fibers were present in the supraoptic decussation, medial forebrain bundle, and stria medullaris thalami.

The localization of NADPH diaphorase neurons in hypothalamic nuclei affected by Alzheimer's disease and other degenerative disorders suggests that further studies of this neuronal subset are warranted     

Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig

Summary This investigation attempted to determine the mode of distribution and synaptic targets of the cartwheel cell axon in the guinea pig dorsal cochlear nucleus (DCoN). Antiserum against PEP-19, a putative calcium-binding neuropeptide, was employed at the light and electron microscopic levels. We show that in the hindbrain of the guinea pig, cerebellar Purkinje cells and DCoN cartwheel cells are the most densely immunoreactive neurons. The PEP-19 immunoreaction product is localized to all neuronal compartments of these cells. Primary targets of cartwheel cell axons are the DCoN pyramidal cells, the large efferent neurons of layer 2. These neurons receive numerous immunoreactive synaptic boutons on their cell bodies and apical and basal dendritic arbors. A PEP-19-immunoreactive axonal plexus, largely formed by cartwheel cell axons, highlights layer 3, co-extensively with the basal arbors of pyramidal cells. This plexus is oriented predominantly in the transstrial plane of the DCoN, in parallel with the sheetlike basal dendritic arbor of pyramidal neurons and with the isofrequency bands of primary cochlear nerve fibers. PEP-19-positive boutons contain pleomorphic synaptic vesicles and form symmetric synaptic junctions, indicative of inhibitory innervation. In addition, immunoreactive boutons, similar to those synapsing on pyramidal neurons, were observed on the cell bodies and main dendritic trunks of cartwheel neurons, indicating a system of recurrent collaterals. Furthermore, a small number of PEP-19-positive axons of unknown origin reach the caudal rim of the posteroventral cochlear nucleus. Within the territory of distribution of the cartwheel cell axon are the dendrites of at least two other types of DCoN neuron, the vertical cells of Lorente de Nó and the giant cells. These neurons may represent additional targets of the cartwheel cell axon, but this remains to be ascertained with specific methods. Our data demonstrate that the cartwheel neurons modulate the activity of pyramidal neurons and, therefore, play a key role in shaping the output of the DCoN superficial layers.     

Ultrastructural immunocytochemistry for glycine in neurons of the dorsal cochlear nucleus of the guinea pig

Neurons in the dorsal cochlear nucleus of the guinea pig were classified according to their positivity to the inhibitory neurotransmitter glycine, ultrastructure and projections to the inferior colliculus as indicated by tract-tracing and ultrastructural immunocytochemistry. Only some pyramidal and few giant cells, surrounded by glycinergic boutons containing flat and pleomorphic vesicles, projected to the inferior colliculus as glycine-negative excitatory cells. Smaller neurons in superficial layers of the dorsal cochlear nucleus did not project to the inferior colliculus, and were recognized as glycine-negative granule and unipolar brush cells. Few glycinergic, inhibitory neurons among granule cells were indicated as Golgi-stellate neurons. All small neurons associated to the granule cell areas received few, mainly glycinergic synapses, and their dendrites contacted large boutons (mossy fibers). Other medium-large glycine positive neurons in the superficial (cartwheel) and deep layers (tuberculo-ventral and large-giant) of the dorsal cochlear nucleus did not project to the inferior colliculus. Giant-large glycinergic neurons surrounded by sparse axo-somatic, mostly glycinergic synapses, probably represent commissural neurons projecting to the contralateral cochlear nucleus. Rare boutons, possibly descending from the inferior colliculus, were seen onto pyramidal cells or their dendrites, and these boutons mainly stored glycine positive pleomorphic vesicles or glycine negative round vesicles. No descending mossy fibers storing round vesicles were labelled from the central nucleus of the inferior colliculus. These observations suggest that very few terminals in the dorsal cochlear nucleus of the guinea pig are derived from the inferior colliculus.     

Acetylcholinesterase-rich pyramidal neurons in Alzheimer's disease.

The distribution of acetylcholinesterase (AChE)-rich pyramidal neurons was studied in the cortices of 7 Alzheimer's Disease (AD) patients and 4 normal-aged subjects. Both groups showed a characteristic distribution of these neurons with the highest density in motor and premotor areas, moderate density in association cortices, and low density in limbic-paralimbic areas. Three areas (Brodmann areas 6,22, and 24) were chosen for quantitative analysis. The number of pyramidal neurons that display an AChE-rich staining pattern was significantly reduced in AD patients. Nerve cell density was not significantly different in adjacent Nissl-stained sections. The density of AChE-rich (cholinergic) fibers was also decreased in all three cortical areas of the AD patients but was not correlated with the number of AChE-rich neurons. Loss of AChE-rich neurons was more pronounced in areas with high counts of tangles. These findings show that layer 3 and 5 pyramidal neurons in AD display a reduction of AChE activity. This phenomenon can not be attributed to the well known loss of cortical neurons or cholinergic innervation in AD.     

Origin, prenatal development and structural organization of layer I of the human cerebral (motor) cortex

Summary The composition and structural organization of layer I of the human motor cortex were studied throughout the course of prenatal cortical neurogenesis with the rapid Golgi method. The components of layer I are six. The specific afferents of layer I (primitive corticipetal fibers) and the Cajal-Retzius neurons are its essential intrinsic components, while the apical dendritic bouquets of all pyramidal neurons and the axonic terminations of all Martinotti neurons are its essential extrinsic elements. These four components are recognized throughout the entire course of prenatal cortical neurogenesis. The small neurons and terminals from afferent systems of lower cortical strata, which are incorporated into layer I late in cortical neurogenesis, represent its non-essential components. The specific afferents of layer I are the first corticipetal fibers to arrive at the developing telencephalic vesicle marking the beginning of cortical neurogenesis. These primitive fibers extend throughout the surface of the cerebral vesicle establishing an external white matter. They are considered to be the stimulus for the development and maturation of the Cajal-Retzius neurons. Together they form a primitive cortical organization, the primordial plexiform layer, which precedes the appearance of the cortical plate and is considered to be common to and shared by amphibians, reptiles and mammals including man. Layer I evolves from this primordial cortical lamination. The Cajal-Retzius neurons are all characterized by a single descending axonic process which becomes a long horizontal (tangential) fiber in the lower half of layer I. Although the body and main dendrites of these neurons are only found at strategic and old cortical regions (e.g. the motor, acoustic and visual areas) their long horizontal axons extend, anteroposteriorly, throughout the entire surface of the cerebral cortex and establish synaptic connections with the apical dendrites of all pyramidal neurons regardless of location, cortical depth or functional role.In the course of cortical development, all developing pyramidal neurons ascend through the cortical plate in order to establish primary synaptic contacts with layer I. Only then, do they become ready to be displaced downward by the arrival of the next set of migrating neuroblasts. All pyramidal neurons of the cerebral cortex are actually suspended from layer I anchored to it by their apical dendritic bouquets. The need for all pyramidal neurons to reach and establish original synaptic connections with layer I could explain the remarkable inside-out formation of the cortical plate. This fact could also explain the characteristic shape of these neurons, as well as their abundance, structural uniformity and universal radial orientation to layer I. The functional role of layer I seems to be the spreading of the same kind of primitive information to all pyramidal neurons of the cerebral cortex whether they be motor, sensory, acoustic, visual or associational in nature, or whether they be large or small.The observations presented in this study further corroborate the concept of the dual origin of the mammalian cerebral cortex. The study emphasizes the important role played by layer I in the overall organization of the cerebral cortex. It proposes that in the course of cortical neurogenesis all future pyramidal neurons are attracted to layer I where they establish original synaptic connections and all receive from it the same kind of primitive information needed for their maturation. There seems to be no obvious reason to believe that the original synaptic contacts established between all pyramidal neurons and layer I disappear in the course of cortical neurogenesis. On the contrary, the progressive growth of the apical dendritic bouquets within layer I seems to indicate that they actually expand.This work has been supported by The National Institute of Child Health and Human Development (Grant #09274) NIH. U.S.A.     

Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine

Summary Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA₁ and of the CA₃ regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA₃ without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA₃ pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA₃ than CA₁ pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA₃ pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA₃ region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified.     

Prenatal cocaine exposure produces consistent developmental alterations in dopamine-rich regions of the cerebral cortex

Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical alterations in the dopamine-rich anterior cingulate cortex of offspring. These effects include increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increases in parvalbumin expression in the dendrites of interneurons, and increases in detectable GABAergic neurons. We have now examined multiple cortical regions with varying degrees of catecholaminergic innervation to investigate regional variations in the ability of prenatal cocaine exposure to elicit these permanent changes. All regions containing a high density of tyrosine hydroxylase-immunoreactive fibers, indicative of prominent dopaminergic input, exhibited alterations in GABA and parvalbumin expression by interneurons and microtubule-associated protein-2 labeling of apical dendrites of pyramidal neurons. These regions included the medial prefrontal, entorhinal, and piriform cortices. In contrast, primary somatosensory, auditory and motor cortices exhibited little tyrosine hydroxylase staining and no measurable cocaine-induced changes in cortical structure.From these data we suggest that the presence of dopaminergic afferents contributes to the marked specificity of the altered development of excitatory pyramidal neurons and inhibitory interneurons induced by low dose i.v. administration of cocaine in utero.     

脑缺血时大鼠海马及其生长抑素神经元的超微结构改变

夹闭大鼠双侧颈总动脉２ｈ，对海马ＣＡ１区进行免疫电镜观察，可见实验组ＣＡ１区部分锥体细胞的胞核固缩、核染色质溶解、细胞器减少或消失；部分神经纤维的髓鞘显示轻度变性图像；部分神经末梢变性；星形胶质细胞突起肿胀；小胶质细胞活跃并包裹断离的髓鞘；生长抑素免疫反应阳性神经末梢比对照组显著增多，生长抑素阳性轴突可与阴性树突形成轴－树突触。以上结果提示：缺血可导致海马ＣＡ１区神经元发生不同程度的损伤和胶质细胞     

Prenatal ontogenetic history of the principal neurons of the neocortex of the cat (Felis domestica) a golgi study

Summary The individual prenatal ontogenetic history of the horizontal neurons (the Cajal-Retzius cells) of layer I, the Martinotti neurons of layer VI, the pyramid-like neurons (the polymorphous or spindle cells) of layer VI, and the pyramidal neurons of layer V of the cat neocortex have been investigated. These neurons undergo, in the course of prenatal ontogenesis, a series of significant changes in their dendritic and axonic arborizations resulting in their complete structural transformation. Some of these changes have led to the appearance of new types of neurons quite different from the original in their morphological features as wells as in the territory of distribution of their axons. The horizontal neurons of layer I (superficial plexiform layer) come to assume the morphological characteristics of Cajal-Retzius cells late in prenatal ontogenesis. Also, the pyramid-like neurons of layer VI (deep plexiform layer) acquire the features of polymorphous (spindle) neurons of layer VI late in prenatal neocortical ontogenesis.Certainly, the resulting functional transformations that these neuronal changes cause are important and of great significance in the understanding of the organization of the mammalian neocortex. In the course of prenatal ontogenesis the following occur: the horizontal neurons of layer I lose their axonic connections with layer VI and acquire an increasing relevance in the structural organization of layer I; the pyramid-like neurons of layer VI lose their axonic and dendritic connections with layer I and undergo pronounced regressive changes in their dendritic and axonic arborizations; and the Martinotti neurons lose their axonic connections with layer I and also undergo regressive changes in their dendritic arborizations. In addition, the structural-functional interrelationships among these three neurons, which are quite prominent during early neocortical ontogenesis, fade away in the course of late prenatal ontogenesis and possibly disappear altogether by the time of birth in the cat. These three neurons are the basic neuronal elements of the early, precallosal organization (the primordial neocortical organization) of the mammalian neocortex. Phylogenetically, these three types of neurons are very old ones and have been described in the cerebral cortices of amphibians and reptiles. Therefore, it is not surprising that the early, precallosal organization of the mammalian neocortex should resemble the structural organization of the reptilian (general cortex) neocortex.It is postulated in this communication that these neuronal transformations are the result of a restructuring in the organization of the mammalian neocortex which follows the arrival of the callosal fibers and of a new type of corticipetal fibers at the pyramidal plate. this restructuring represents a transformation of the fibrillary-neuronal structure of the mammalian neocortex from its early, precallosal (reptilian) organization into a more distinctly mammalian one. The mammalian neocortical organization is characterized by the sequential maturation of several strata of true pyramidal neuronal systems. In the course of prenatal ontogenesis the fibrillar and neuronal elements of the early, precallosal neocortical organization lose progressively their relevance in the structural organization of the mammalian neocortex while the new pyramidal neuronal systems acquire an increasing relevance in it.Supported by Grant HD-03298 and by General Research Support Grant FR-05392 from the General Research Branch, National Institutes of Health.