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Neuronal maps of the frontal ganglion of the cockroach, Periplaneta americana, prepared by heavy metal iontophoresis.

Neurons in whole mount preparations of the frontal ganglion (FG) of the cockroach, Periplaneta americana, were mapped with the aid of cobalt chloride staining and silver intensification techniques. Eighty-six neurons were counted in the FG after staining with reduced methylene blue. The cell size ranged between 20 to 35 microns in diameter. Of the somata located in the FG, 44 were found to contribute their fibers to the nervus recurrens, 26 to the right frontal commissure, 28 to the left frontal commissure, and 6 to the nervus connectivus. In addition, a few neurons presumably from the tritocerebral region also contribute their fibers in the formation of nervus connectivus. The present study has helped delineate the neuronal connections of the FG with the brain and neuroendocrine system (corpora cardiaca and corpora allata). This information will be useful in facilitating the positioning of microelectrodes in our future electrophysiological experiments.

Animals↗

Neurons in Golgi-stain-like images revealed by GFP-adenovirus infection in vivo.

Neurons in the adult brain have a very complex morphology with many processes, including tremendously long axons. Since dendrites and axons play key roles in the input and output of neural information, respectively, the visualization of complete images of these processes is necessary to reveal the mechanism of neural information processing. Here we made a recombinant adenovirus vector which encodes green fluorescent protein (GFP) tagged with a palmitoylation site, a membrane-targeting signal, produced specific antibodies to GFP, and used them as probes for staining the nervous system. In the neocortex, after injection of the recombinant virus and immunoperoxidase staining with the antibodies, many different types of cells were labeled in a Golgi stain-like fashion. Although the number of labeled cells varied depending on the amount of virus injected, the recombinant virus was considered to be infectious to cortical neurons of all cell types without selectivity. In contrast, the viral infection in the cerebellar cortex and superior cervical ganglion showed some selectivity toward the cell type. It is expected that this recombinant virus will be a useful tool for the morphological analysis of neuronal connections, especially the analysis of microcircuitry in the cerebral cortex.

Adenoviridae↗

Neurotrophins and plasticity in the visual cortex.

The visual cortex is one of the favorite models for the study of experience-dependent changes in neuronal structure and function. A number of recent investigations indicate that the neurotrophic factors of the nerve growth factor family (neurotrophins) play a pivotal role in visual cortical plasticity. Neurotrophins and their receptors are present in the cortex during the critical period for plasticity, and neurotrophin levels are regulated by electrical activity. Neurotrophins modulate synaptic transmission and patterns of neuronal connectivity in the cortex. This review summarizes the in vivo and in vitro data that demonstrate the involvement of neurotrophins in visual cortical plasticity and discusses the possible mechanisms of their action.

Animals↗

Anatomical organization of antennal lobe projection neurons in the moth Heliothis virescens.

A prerequisite for understanding how odor information is coded in the central nervous system is to know the morphology and spatial relationship of the principal neurons forming the olfactory pathways. The present account provides an anatomical description of the morphology of the neuronal connections between the antennal lobe and the protocerebrum in the moth Heliothis virescens, a species used for studies of olfactory processing and learning. Intracellular labeling and antennal lobe focal injections with dextran fluorescent markers were combined with neuropil immunostaining and three-dimensional reconstructions. The experiments revealed four antennocerebral tracts, the inner, middle, outer, and dorsomedial, and eight morphological types of projection neurons in addition to a neuron with an unpaired median soma in the subesophageal ganglion. Multiglomerular projection neurons, present in all but the dorsomedial antennocerebral tract, project in several olfactory foci of the protocerebral neuropil. With few exceptions, these neurons do not innervate the calyces of the mushroom body. Uniglomerular projection neurons appear most numerous in the inner antennocerebral tract but are also present in the outer and dorsomedial tracts. These neurons always ramify in the calyces of the mushroom body and in the lateral horn. The projection areas of the neurons following different tracts are largely separated in the secondary olfactory centers. This is most evident in the lateral horn, whereas, in the calyces, the axonal ramifications are more intermingled. The mushroom body architecture, revealed by neuropil immunolabeling, showed striking similarities to that of other lepidopteran species as well as insects of other taxa.

Afferent Pathways↗

Afferent connections of the neurons in the Forel's field of H in cat.

An anatomico-physiological analysis was made to elucidate afferent connections of the neurons in the Forel's field of H (FFH) by horseradish peroxidase retrograde tracing technique and by evoked potential technique. 1) The FFH neurons receive fibers from the neocortex (layer V) and brainstem reticular formations. 2) Physiological projections from the mesencephalic reticular formation to the FFH as well as to the motor cortex were ipsilateral, but those from the pons and medulla oblongata were bilateral. 3) These data will suggest that the FFH neurons are in junction of the cortico-reticular connections and play an important role in the maintenance of an epileptic excitability of the neocortical system as suggested by Jinnai and Mukawa.

Afferent Pathways↗

Anatomical correlates of the functional organization in the human occipitotemporal cortex.

The connectivity between functionally distinct areas in the human brain is unknown because of the limitations posed by current postmortem anatomical labeling techniques. Diffusion tensor imaging (DTI) has previously been used to define large white matter tracts based on well-known anatomical landmarks in the living human brain. In the present study, we used DTI coupled with functional magnetic resonance imaging (fMRI) to assess neuronal connections between human striate and functionally defined extrastriate ventral cortical areas. Functional areas were identified with conventional fMRI mapping procedures and then used as seeding points in a DTI analysis to ascertain connectivity patterns between cortical areas, thus yielding the pattern of connections between human occipitoventral visual areas in vivo.

Adult↗

Oligophrenin-1, a Rho GTPase-activating protein (RhoGAP) involved in X-linked mental retardation, is expressed in the enteric nervous system.

Oligophrenin-1 is a RhoGTPase-activating protein (RhoGAP) that is involved in the regulation of shape changes in dendritic spines, and outgrowth of axons and dendrites in the brain. These changes in neuronal morphology are central to the mechanisms of plasticity, learning, and memory. Although the enteric nervous system also exhibits long-term changes in neuronal function, the expression and involvement of oligophrenin-1 has not previously been investigated. We show by RT-PCR analysis that oligophrenin-1 mRNA is expressed in the myenteric plexus (MP) of the guinea pig ileum. Sequencing of RT-PCR products showed that guinea pig oligophrenin-1 mRNA is 98% and 87% homologous to human and mouse oligophrenin-1, respectively, except that a 42 bp sequence is absent from the guinea pig mRNA. This 42 bp sequence codes for a sequence of 14 amino acids located near the carboxy-terminal end of the RhoGAP domain in the human sequence. An antibody that recognizes human oligophrenin-1 identified a 91 kDa protein band in rat and mouse brain lysates and in guinea pig sciatic nerve, and a 36 kDa protein band in both purified enteric ganglion cell and brain lysate from guinea pig. Oligophrenin-1 is localized specifically to neurons and varicose axons in the MPs and submucosal plexuses (SMPs) of the guinea pig and rat, but is not detectable in glial cells, smooth muscle, or other cell types. These findings indicate that oligophrenin-1 is expressed in the enteric nervous system, where it may regulate morphological changes in axons and dendrites, and thus modulate neuronal connectivity.

Animals↗

Wiring, dysmorphogenesis and epilepsy: a hypothesis.

Cerebral cortical dysgenesis has been found by magnetic resonance imaging to be the second most common pathology underlying medically refractory chronic partial epilepsy. Patients with the latter condition form the largest group in specialist epilepsy clinics. The pathogenesis of the epilepsy in cortical dysgenesis remains largely obscure. The most popular current hypothesis holds neuronal misconnection secondary to neuronal malpositioning culpable for seizure activity. However, a review of the published literature of cortical dysgenesis and an analysis of newer magnetic resonance and histopathological data, suggests that this view is no longer tenable. A modified hypothesis is proposed in which neuronal connectivity itself is postulated to be the primary motive force in both cerebral morphogenesis and epileptogenesis in cases of cortical dysgenesis. This hypothesis leads to the generation of a model for cortical development and directly testable predictions of intercellular connectivity, as well as a potential tool for the prediction of the possibility of freedom from seizure activity after surgical resection of dysgenetic lesions in individual cases.

Animals↗

Interactions of neural networks: models for distraction and concentration.

We present a model of neural group interactions, which are projections from one neural network (network B) of McCulloch-Pitts neurons connected via a Hebbian rule, to another network (network A) of the same structure. We first consider the case in which the projecting network B is in a pattern different from the initial attracting state of network A. A critical projecting strength lambda c is found such that for lambda below this value there exists a noise threshold sigma lambda corresponding to each lambda. For the case where lambda less than lambda c and the noise level sigma less than sigma lambda, there are two possible retrievals, with different probabilities: the initial attracting state of network A and the projecting pattern. If lambda less than lambda c and sigma greater than sigma lambda, stable states of network A disappear. In the case lambda greater than lambda c, network A is pulled out of its initial basin of attraction and into that of the projecting pattern. This analysis provides a model for distraction. Second-order interactions reduce the distraction. When the projecting network B is in the same pattern as the initial attracting state of network A, the projection acts as an external reinforcement, which enables network A to retrieve in highly noisy conditions. Sharp noise thresholds for nonzero retrievals are shown to be eliminated by the projection. Higher-order connectivity improves the retrieval ability of the network. The second case serves as a model of concentration. We discuss the model of distraction and concentration (i) in connection with common experience of expectation of recognition and (ii) in connection with recent T-maze experiments on infant rats; finally, we suggest a refined version of the Bruner-Potter experiment to test our prediction of the disappearance of hysteresis.

Animals↗

Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors.

Local GABA (gamma-aminobutyric acid) circuits contribute to sensory experience-dependent refinement of neuronal connections in the developing nervous system, but whether GABAergic synapses themselves can be rapidly modified by sensory stimuli is largely unknown. Here we report that repetitive light stimuli or theta burst stimulation (TBS) of the optic nerve in the developing Xenopus retinotectal system induces long-term potentiation (LTP) of glutamatergic inputs but long-term depression (LTD) of GABAergic inputs to the same tectal neuron. The LTD is due to a reduction in presynaptic GABA release and requires activation of presynaptic NMDA (N-methyl-D-aspartate) receptors (NMDARs) and coincident high-level GABAergic activity. Thus, the presynaptic NMDAR may function as a coincidence detector for adjacent glutamatergic and GABAergic activities, leading to coordinated synaptic modification by sensory experience.

Animals↗

Glial control of neuronal development.

Reciprocal interactions between differentiating glial cells and neurons define the course of nervous system development even before the point at which these two cell types become definitively recognizable. Glial cells control the survival of associated neurons in both Drosophila and mammals, but this control is dependent on the prior neuronal triggering of glial cell fate commitment and trophic factor expression. In mammals, the growth factor neuregulin-1 and its receptors of the ErbB family play crucial roles in both events. Similarly, early differentiating neurons and their associated glia rely on reciprocal signaling to establish the basic axon scaffolds from which neuronal connections evolve. The importance of this interactive signaling is illustrated by the action of glial transcription factors and of glial axon guidance cues such as netrin and slit, which together regulate the commissural crossing of pioneer axons at the neural midline. In these and related events, the defining principle is one of mutually reinforced and mutually dependent signaling that occurs in a network of developing neurons and glia.

Animals↗

Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in differentiated human neurones: implications for inflammation-related axonal regeneration in the central nervous system.

Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation-related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal differentiation; and (iii) their regulation in NTera2-derived differentiated neurones (NTera2-N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post-traumatic inflammatory lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis, the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non-neural cell lines. By Northern blot analysis, the levels of Nogo-A mRNA were elevated markedly in NTera2 cells following RA-induced neuronal differentiation, accompanied by an increased expression of the neurite growth-associated protein GAP-43 mRNA. In contrast, Nogo-A, Nogo-B, NgR and GAP-43 mRNA levels were unaltered in NTera2-N cells by exposure to basic fibroblast growth factor, brain-derived neurotrophic factor, glia-derived neurotrophic factor, tumour necrosis factor-alpha, interleukin-1beta, dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate. These results indicate that both Nogo-A and NgR mRNA are coexpressed in various human cell types, including differentiated neurones, where their expression is unaffected by exposure to a panel of cytokines and neurotrophic factors which might be involved in inflammation-related axonal regeneration in the CNS.

Axons↗

Possible synaptic connections of expiratory neurons in the medulla of newborn rat in vitro.

To elucidate synaptic interactions between expiratory (Exp) and other respiratory neurons in the ventrolateral medulla of brain stem-spinal cord preparations from newborn rats, we analyzed postsynaptic potentials in Exp and a subclass of inspiratory (Insp) neurons using whole-cell recordings. About 72% of the Exp neurons (Exp-p-i) showed Cl--dependent synaptic inhibition during the Insp and pre/post-Insp phases, corresponding to the active phase of the Insp and pre-inspiratory (Pre-I) neurons, respectively. The other 28% neurons (Exp-i) received Cl--dependent inhibition during the Insp phase only. Some Insp neurons showed reversed IPSPs during the active phase of Exp-p-i after Cl-loading. We suggest the existence of inhibitory connections from Pre-I and Insp to Exp and from Exp to Insp neurons. Basic synaptic connections among respiratory neurons similar to those in intact adult mammals may already exist in newborn rats.

Animals↗

Transhemispheric horizontal channels for transmission of epileptic information.

1) To gain insight into the complex pathophysiology of epilepsy in the human brain, the synthesis of information derived from various animal models representing appropriate components of human epileptic seizure is required. For epileptic seizure propagation, the availability of anatomical pathways and their physiological connectivity according to the site of seizure origin must be considered. The reason for the notion of a preferential nature of certain pathways over others remains unknown but may be due, in part, to past history and the participation of a genetically-determined differential susceptibility. In this context, the following factors need to be considered: a) the significance of use-dependent functional/structural change of the neuronal system, b) the importance of understanding the divergent nature of neuronal connectivity, the potential role of genetic predisposition, and c) the morphological difference which exists according to ascending phylogenesis and hence the presumable functional difference across the species. 2) The corpus callosum is the major and rapid route of transhemispheric transmission of epileptic seizure in man. In the case of seizure of temporal lobe origin, its transhemispheric transmission may use the temporalipsilateral frontal through the corpus callosum to the contralateral frontal and then to the contralateral temporal limbic system. In contrast, the significance of the anterior commissure and the hippocampal commissure in man is debatable since both of these pathways have a very definite regressive tendency according to ascending phylogenesis. The specific reason why these pathways are sometimes used in a minority of temporal lobe seizure cases remains unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Magnetic resonance imaging of the visual pathways in human albinos.

Neuroanatomical and electrophysiological studies of albino visual pathways have demonstrated that retinogeniculate axons arising from the temporal retina decussate abnormally in the optic chiasm to synapse in the contralateral lateral geniculate nucleus (LGN). Anomalies in the LGN secondarily disrupt normal geniculo-cortical and interhemispheric cortico-cortical (callosal) visual connections. It is not known whether retinogeniculate misrouting affects the size or configuration of the afferent visual pathways in human albinos. We used T1-weighted coronal and sagittal magnetic resonance imaging (MRI) to examine the prechiasmatic intracranial optic nerves, optic chiasm, and corpus callosum in 10 human albinos. In all subjects, these structures were normal in size and configuration. Despite the complex cascade of aberrant central neuronal connections, the human albino visual pathways and their interhemispheric connections appear normal in size and configuration when viewed with MRI.

Adolescent↗

The gas7 protein potentiates NGF-mediated differentiation of PC12 cells.

The growth-arrest-specific protein gas7 is required for morphological differentiation of cultured mouse cerebellar neurons and PC12 cells. Moreover, its overexpression in various cell types induces neurite-like outgrowth. The role of gas7 in neuronal differentiation was further characterized by adenovirus-mediated overexpression in PC12 cells and quantification of the expression of various neuronal markers, in the absence and presence of different concentrations of nerve growth factor (NGF). The potential neuroprotective activity of gas7 against various neurotoxic insults was also assessed. In addition to promoting the formation of neurite-like extensions, overexpression of gas7 potentiated NGF-mediated neuronal differentiation of PC12 cells, as shown by the enhanced expression of the neuronal proteins betaIII-tubulin, synaptotagmin, alpha7 subunit of the acetylcholine receptor, and dihydropyrimidinase related protein-3. This effect was exerted independently of cell cycle progression, as gas7 did not affect proliferation of PC12 cells. While some differentiation enhancers protect PC12 cells against lethal insults, gas7 overexpression in PC12 cells did not protect against oxygen-glucose deprivation, the calcium ionophore A23187, or the nitric oxide donor sodium nitroprusside, suggesting that gas7 is not neuroprotective. The ability of gas7 to potentiate neuronal differentiation makes it a potential therapeutic target to promote re-establishment of neuronal connections in the injured or diseased brain, such as following stroke.

Animals↗

Development of the human lateral cuneate nucleus: a morphometric evaluation.

The morphometric development of the human lateral cuneate nucleus was examined in nine fetuses and neonates at 18-40 weeks of gestation, a 2-month-old infant and a 63-year-old adult. The authors observed serial sections of the brain containing lateral cuneate nucleus and measured the volume of nuclear column and the number, cell body area and perimeter of neurons using a microscope with a drawing tube and an image-analyzing computer system. A morphometric evaluation revealed that a turning point in the development of the human lateral cuneate nucleus occurring at 30 WG, as this marks the beginning of a gradual increase in the average area and average perimeter; And it is the point at which the neuropil index suddenly increases sharply, to fall back down to lower levels afterwards. The establishment of a neuronal connection between the lateral cuneate nucleus and the cerebellum, which is necessary for proper performance of movements in the upper part of the body.

Afferent Pathways↗

Blink reflex in motor neuron disease.

The aim of the study was to analyse the diagnostic value of blink reflex (BR) in motor neuron disease (MND). We studied 25 patients with MND including amyotrophic lateral sclerosis (ALS) in 18 patients, primary muscular atrophy (PMA) in 4 patients, and primary lateral sclerosis (PLS) in 3 patients and 12 healthy volunteers. The blink reflex was obtained in typical way. In ALS group, statistically significant increase in latency and decreased amplitude of R2 responses were found compared to the control group (p < 0.05), whereas BR in patients with PLS and PMA was within normal limits. The presence of low amplitude of R2 responses in patients with ALS may suggest loss of lower brainstem neurons connecting trigeminal and facial system, and probably also decreased facilitator effect of central nervous system on reticular formation in the brainstem.

Adolescent↗