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Biomedical subjects

J Meek

Publications and source records attributed to J Meek.

At least 37 records · Page 2Linked to original sources
PubMed1994

The role of motor command feedback in electrosensory processing.

Sensory motor-coordination and the descending modulation of sensory perception can be particularly well studied in the mormyrid electrosensory lateral line lobe (ELL). In this first order sensory processing network, electroreceptive primary afferent input is integrated with a corollary discharge signal which modulates neuron excitability immediately after the generation of an electric organ discharge. Corollary discharge feedback to the electrosensory lobe allows the brain to distinguish between reafferent sensory input, generated by autostimulation of cutaneous electroreceptors (resulting from the fish's own electric discharge) and exafferent sensory input, evoked by stimulation of the same cutaneous electroreceptors by an external electric source. Mechanisms of this type define the context of incoming sensory information and are the first step in the dynamic regulation of perception. The corollary discharge pathway originates from a collateral branch of the electromotor command neuron axons. It is relayed via bulbar and mesencephalic command-associated nuclei and reaches the ELL by way of projections from the cerebellar posterior granular eminence to the superficial layer of the ELL, and from juxtalobar and juxtalemniscal nuclei to the deeper layers of ELL. ELL is a geometrically organized laminar structure containing a variety of cell types. A number of them combine a spiny dendritic tree in the superficial molecular layer with non-spiny basal dendrites in plexiform or deeper layers. Sensory input may reach the basal dendrites of these neurons either directly or indirectly, via granule cells in the deeper layers of ELL, on which the primary afferent fibers terminate. All neurons recorded intracellularly in the ELL show strong interaction between electrosensory and corollary discharge input. Corollary discharge gating of sensory processing is plastic and depends on dynamic sensory-motor association.

Animals↗
PubMed1994

Microcircuitry of the mormyrid electrosensory lateral line lobe.

The mormyrid electrosensory lateral line lobe (ELL) is a laminated structure in the dorsal rhombencephalon receiving topographically ordered primary sensory input from electroreceptors and corollary signals from the electromotor command nucleus. The structural basis of the integration of these and other inputs was investigated at the light and electron microscopical level using neuroanatomical tracers, immunohistochemistry and Golgi-impregnations. The ELL contains at least 14 distinct cell types. These include small granule cells receiving primary afferent input, GABA-ergic spiny interneurons and glutamatergic projection neurons integrating sensory input and descending feedback, and deep intrazonal neurons. Present knowledge of the synaptic organization of the ELL afferents and cell types allows for a preliminary scheme of its microcircuitry.

Animals↗
PubMed1993

Distribution of noradrenaline-immunoreactivity in the brain of the mormyrid teleost Gnathonemus petersii.

The distribution of noradrenaline-immunoreactivity in the brain of the mormyrid fish Gnathonemus petersii was studied in order to evaluate the noradrenergic innervation of a number of specialized mormyrid brain regions, including electrosensory centers and a gigantocerebellum. Noradrenaline-immunoreactive (NAi) neurons occur in the hypothalamic paraventricular organ (PVO), the locus coeruleus, and the caudal rhombencephalon. In the PVO, NAi cerebrospinal fluid (CSF)-contacting neurons are located in the same regions where dopamine- and serotonin-containing CSF contacting neurons occur. The locus coeruleus consists, on each side, of at least 30 rather large NAi neurons with ventrolaterally directed dendrites and dorsolaterally coursing axons. In the caudal rhombencephalon, NAi neurons are located in the transition region between the ventromedial motor zone and the dorsolateral sensory zone. The density of NAi fibers is very high in the efferent tract of the locus coeruleus, the medial forebrain bundle, and two telencephalic, one preoptic, and one rhombencephalic subependymal axonal plexus. A marked NAi innervation is present in the dorsomedial and ventral telencephalon, the preoptic region, periventricular hypothalamic and thalamic regions, the midbrain tectum, cerebellar granular layers, the electrosensory lateral line lobe, the rhombencephalic transition region between the sensory and motor zones, and the area postrema. Other regions are more sparsely innervated by NAi fibers, but regions completely devoid of NAi fibers were not observed. Interestingly, NAi fibers form large club endings in some subdivisions of the precerebellar nucleus lateralis valvulae, and parallel fibers in the cerebellar granular layer. Comparison with the distribution of NAi or dopamine-beta-hydroxylase-immunoreactivity in other species shows that all teleosts studied to date have noradrenergic cells in the locus coeruleus and the caudal rhombencephalon. However, NAi CSF-contacting PVO cells have been described only in the teleost Gnathonemus petersii and the lizard Gekko gecko (Smeets and Steinbusch: J. Comp. Neurol. 285:453-466, '89). It is possible that they might pick up catecholamines as well as serotonin from the CSF, into which monoamines might be released by telencephalic and preoptic subependymal axonal plexuses.

Anatomy, Comparative↗
PubMed1993

The hypothalamic aggression region of the rat: observations on the synaptic organization.

Comparison of detailed physiological and morphological data shows that the hypothalamic aggression region in the rat largely coincides with the intermediate hypothalamic area. This region has a neuronal density of about 35.10(3) neurons per mm3, a synaptic density of about 300.10(6) per mm3, and a synapse to neuron ratio of about 9000, including only about 200 axosomatic synaptic contacts per neuron. Septal synaptic contacts in this region originate from unmyelinated axons and are axodendritic of the asymmetrical type, with an average bouton diameter of 785 nm and an average synaptic contact length of 270 nm.

Aggression↗
PubMed1992

Distribution of zebrin II in the gigantocerebellum of the mormyrid fish Gnathonemus petersii compared with other teleosts.

Immunocytochemistry has demonstrated unexpected heterogeneity among cerebellar Purkinje cells. For example, monoclonal antibody Mab anti-zebrin II reveals parasagittal bands of immunoreactive Purkinje cells in the mammalian cerebellum, but reveals a non-sagittal cerebellar compartmentation pattern in goldfish and gymnotiform fish. The present paper investigates the cerebellar compartmentation pattern, as reflected in the zebrin II distribution, in two other teleosts, the electric mormyrid fish Gnathonemus petersii with its large and regularly built gigantocerebellum, and the electrosensory osteoglossomorph teleost Xenomystis nigri, by using light as well as electron microscopic immunohistochemical techniques. Zebrin II is expressed only in Purkinje cells, where it is present in the cytoplasm of all neuronal compartments, including spines, distal and proximal dendrites, the cell body, and the initial part, as well as terminal boutons of the axon. Other types of cerebellar neurons, including the eurydendroid projection neurons, are zebrin II-negative. In Gnathonemus, zebrin II-positive Purkinje cells are present in the large caudolateral part of the valvula, in lobes C2, C3, and C4 of the corpus, and in the anterior as well as the posterior part of the caudal cerebellar lobe. Zebrin II-negative Purkinje cells are present in a continuous region encompassing the rostromedial part of the valvula, the lobus transitorius, lobe C1 and the ventral part of lobe C2, and in a small, lateral zone of the posterior part of the caudal lobe. In Xenomystis, all Purkinje cells, including those in the medial valvula and the posterior part of the caudal lobe, appear to react with mab anti-zebrin II. This more widespread distribution may be due to the presence of a second antigenic polypeptide in this species. On the basis of the present findings, it is concluded that the mormyrid lobus transitorius, lobe C1, and the ventral part of lobe C2 probably belong to the valvula, while the corpus is restricted to the dorsal part of lobe C2, lobe C3, and lobe C4. The functional significance of zebrin II expression for different subsets of teleostean Purkinje cells remains unclear, since comparisons of different teleosts reveal no general correlation with particular afferent or efferent connections, nor with special morphological features such as a dendritic palisade pattern or different arrangements of the Purkinje cell bodies. A comparison between mammals and teleosts suggests that a distinct parasagittal cerebellar zonation in teleosts is absent, and the major part of the teleostean cerebellum may be considered as a single (midsagittal) cerebellar zone, with about the same width as one mammalian parasagittal zone.

Animals↗
PubMed1992

Why run parallel fibers parallel? Teleostean Purkinje cells as possible coincidence detectors, in a timing device subserving spatial coding of temporal differences.

The present paper explores the possible functional significance of the parallel orientation of parallel fibers in teleostean cerebellar and cerebelloid molecular layers, taking advantage of the restricted width of these molecular layers compared with mammalian ones and several specific configurations of granule cells. These configurations include: (i) a unilateral location, i.e. at only one (lateral) side of the molecular layer, giving rise to parallel fibers without bifurcation in a unidirectional molecular layer, where all parallel fibers conduct signals in the same direction; (ii) a bilateral location at both sides of the molecular layer giving rise to a bidirectional molecular layer where parallel fibers conduct signals in two opposite directions originating from two discrete sources; and (iii) a basal (or sometimes apical) location underneath (or opposite to) the layer of Purkinje cells, giving rise to a bidirectional molecular layer where parallel fibers conduct signals in two opposite directions originating from a continuous range of sources. It is argued that molecular layers with a bilateral location of granule cells, exemplified by the mormyrid lobus transitorius, represent an optimal configuration for the analysis of small temporal differences (up to 4 ms) between inputs to the right and left granule cell mass, by means of detection of the site of coincidence of parallel fiber activity running from left to right and vice versa. Morphological aspects that probably optimize such a function include not only the parallel course and bilateral origin of parallel fibers, but also their small diameter, large number and co-extensive location, as well as the sagittal orientation and the presence of many spines of Purkinje cell dendrites and the presence of stellate and other inhibitory interneurons. The only assumption underlying the present coincidence detection hypothesis is that Purkinje cells are supposed to be maximally stimulated by parallel fiber input when all spines are activated in such a way that their excitatory postsynaptic potentials reach the axon hillock simultaneously. For molecular layers with a unilateral location of granule cells, exemplified by the teleostean torus longitudinalis-tectal marginal parallel fiber system, a similar coincidence detecting mechanism is proposed on the basis of the presence of two populations of parallel fibers with slightly different conduction velocities. Such a system might be suitable to adapt the location of coincidence peaks to topographic maps present in deeper layers of nervous tissue. Molecular layers with basally (or apically) located granule cells as encountered in the teleostean corpus cerebelli, are probably involved in the analysis of specific spatio-temporal input waves directed centripetally towards different Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Comparative aspects of cerebellar organization. From mormyrids to mammals.

Recent progress in the comparative analysis of the vertebrate cerebellar organization shows that the cerebella of different tetrapods have a basically similar intrinsic organization, whereas the cerebellum of fishes displays a number of fundamental differences in this respect. Clear examples of teleostean cerebellar specializations are present in the gigantocerebellum of mormyrids, including a valvula cerebelli, the absence of a parasagittal zonal organization, the presence of eurydendroid projection neurons instead of deep cerebellar nuclei, a precerebellar nucleus lateralis valvulae, olivocerebellar fibers that do not climb into the molecular layer, uni- and bilateral locations of granule cells, parallel fibers without a T-shaped bifurcation and with a coextensive distribution in the transverse plane, and different Purkinje cell arrangements including a dendritic palisade pattern. A theoretical exploration of the possible significance of these configurations suggests that they all might be involved in a single main cerebellar function, i.e. coincidence detection of parallel fiber activity by Purkinje cells.

Animals↗
PubMed1991

Palisade pattern of mormyrid Purkinje cells: a correlated light and electron microscopic study.

The present study is devoted to a detailed analysis of the structural and synaptic organization of mormyrid Purkinje cells in order to evaluate the possible functional significance of their dendritic palisade pattern. For this purpose, the properties of Golgi-impregnated as well as unimpregnated Purkinje cells in lobe C1 and C3 of the cerebellum of Gnathonemus petersii were light and electron microscopically analyzed, quantified, reconstructed, and mutually compared. Special attention was paid to the degree of regularity of their dendritic trees, their relations with Bergmann glia, and the distribution and numerical properties of their synaptic connections with parallel fibers, stellate cells, "climbing" fibers, and Purkinje axonal boutons. The highest degree of palisade specialization was encountered in lobe C1, where Purkinje cells have on average 50 palisade dendrites with a very regular distribution in a sagittal plane. Their spine density decreases from superficial to deep (from 14 to 6 per micron dendritic length), a gradient correlated with a decreasing parallel fiber density but an increasing parallel fiber diameter. Each Purkinje cell makes on average 75,000 synaptic contacts with parallel fibers, some of which are rather coarse (0.45 microns), and provided with numerous short collaterals. Climbing fibers do not climb, since their synaptic contacts are restricted to the ganglionic layer (i.e., the layer of Purkinje and eurydendroid projection cells), where they make about 130 synaptic contacts per cell with 2 or 3 clusters of thorns on the proximal dendrites. These clusters contain also a type of "shunting" elements that make desmosome-like junctions with both the climbing fiber boutons and the necks of the thorns. The axons of Purkinje cells in lobe C1 make small terminal arborizations, with about 20 boutons, that may be substantially (up to 500 microns) displaced rostrally or caudally with respect to the soma. Purkinje axonal boutons were observed to make synaptic contacts with eurydendroid projection cells and with the proximal dendritic and somatic receptive surface of Purkinje cells, where about 15 randomly distributed boutons per neuron occur. The organization of Purkinje cells in lobe C3 differs markedly from that in C1 and seems to be less regular and specialized, although the overall palisade pattern is even more regular than in lobe C1 because of the absence of large eurydendroid neurons. However, individual neurons have a less regular dendritic tree, there is no apical-basal gradient in spine density or parallel fiber density and diameter, and there are no "shunting" elements in the climbing fiber glomeruli.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Dendritic and synaptic properties of collicular neurons: a quantitative light and electron microscopical study of Golgi-impregnated cells.

The present study deals with a light- and electron microscopic morphometric analysis of Golgi-impregnated neurons in the superior colliculus of rats with the purpose to unravel inter- and intralaminar differences in their dendritic and synaptic organization. In particular, layer IV was studied and compared with its boundary layers III and V. The results show that collicular cells in layer IV basically form a homogeneous population with respect to the number of primary dendrites, the total length of impregnated dendrites, and the diameter, ellipticity, and orientation of dendritic fields and somata of Golgi-impregnated neurons. Somata of reconstructed small cells in layer III and IV as well as V have all a similar density of about 40 synaptic contacts per 100 microns2 surface. However, the cell bodies of large multipolar cells in layer V have a slightly but significantly larger synaptic density (about 50 per 100 microns2). Dendrites of large and small collicular cells had no significantly different synaptic densities (43 and 48 per 100 microns2, respectively). In conclusion, the present results show only minor dendritic and synaptic differences between individual cells in the same layer, as well as in neighboring layers, which implies a low degree of cellular and synaptic intra- and interlaminar differentiation. It is discussed that this organization differs markedly from that in other visual centers, including the collicular homologue, the tectum of lower vertebrates, and the mammalian visual cortex, where pronounced inter- and intralaminar differentiations exist. Such an organization may provide a framework of laminar specificity by which distinct cell types may select a restricted set of input out of all information available. The present quantitative investigation suggests that a similar framework is not present in the superior colliculus.

Animals↗
PubMed1990

Synaptic morphometry and synapse-to-neuron ratios in the superior colliculus of albino rats.

The superior colliculus of mammals is generally divided into seven layers on the basis of the distribution of myelinated fibers, which are densely packed in layers III, V, and VII but sparse in the other layers. The laminar distribution of afferents and efferents allows, in addition, for the distinction of a superficial visual zone (layers I-III) and a deeper multimodal and premotor zone (layers IV-VII). Collicular neurons, however, do not show a lamination pattern, but are rather homogeneously distributed with only gradual transitions (Albers et al.: J. Comp. Neurol. 274:357-370, '88). The present study analyses whether the distribution of collicular synapses is correlated with the laminar organization of collicular axons or rather with the more homogeneous distribution of collicular neurons. For this purpose, the size and density of synaptic terminals and contacts as well as synapse-to-neuron ratios were determined in all collicular layers of albino rats by means of quantitative analysis of electron microscopic pictures. The size of presynaptic terminals and contacts does not differ significantly between individual collicular layers. On average, presynaptic terminal diameter is 1,079 nm, and synaptic contact size 338 nm, while 23% of all contacts are of the symmetrical type with pleiomorphic vesicles. The average numerical synaptic density is 422 million per mm3. This value is significantly higher in layers I and II (on average 670 million per mm3) than in layers III-VII (on average 370 million per mm3). The synapse-to-neuron (S/N) ratios calculated show that collicular neurons have on average 6,120 synaptic contacts on their receptive surface. The S/N ratio is lowest in layer III (4,330), while this ratio is highest in layers I and VII (i.e., 8,970 and 8,560 respectively). Layer II has a significantly higher S/N ratio than layer III (i.e., 8,060 and 4,330, respectively). Our results show that the size of synaptic terminals and contacts is not correlated with the different connectivity patterns of the distinct collicular layers. However, the density of synapses as well as the synapse-to-neuron ratios show a certain degree of laminar differentiation. In particular the superficial visual zone appears to be inhomogeneous in this respect, since layers I and II have a significantly higher density of synapses and higher S/N ratios than layer III. The deeper collicular zone is more homogeneously organized with synaptic densities similar to that of layer III and gradually increasing synapse-to-neuron ratios from layer IV to layer VII.

Animals↗
PubMed1989

Distribution of dopamine immunoreactivity in the brain of the mormyrid teleost Gnathonemus petersii.

The distribution of dopamine-containing cell bodies and fibers was studied with aid of specific antibodies against dopamine in the highly developed brain of the weakly electric fish Gnathonemus petersii. In the telencephalon, dopamine-containing cell bodies were observed in a small area, i.e., area ventralis pars dorsalis and supracommissuralis. In the diencephalon, moderate numbers of dispersed dopamine-immunoreactive cells were present in the preoptic region, while large numbers of dopamine-containing neurons occurred in the hypothalamic paraventricular organ and neighbouring regions. The paraventricular organ, located around small (anterior, intermediate, and posterior) recesses contained many dopamine-immunoreactive cerebrospinal fluid-(CSF)-contacting neurons. Dopamine-containing cells were also observed in a magnocellular hypothalamic cell group, in the nucleus of the lateral recess, and in the nucleus posterior tuberis. In the mesencephalon only a few dopamine-containing cells were observed in a dorsal tegmental (possibly pretectal) area, whereas in ventral mesencephalic regions dopamine-containing cells were lacking. More caudally, dopamine-containing cells were observed in the presumed locus coeruleus, in the caudal region of the reticular formation, and in the presumed area postrema. Dopamine-immunoreactive fiber density was very high in the medioventral hypothalamus and in the preoptic region, where a dense subependymal plexus was observed along the preoptic recess. Such a plexus was also present in the caudal rhombencephalon, where it probably arises from the area postrema. Moderate numbers of dopamine-immunoreactive fibers were present in medioventral parts of the brain along its total rostrocaudal extent as well as in several subnuclei of the torus semicircularis, in the tectum mesencephali, and in the medial part of the dorsal telencephalic area. Other parts of the dorsal telencephalic area, as well as the large cerebellum and the electrosensory lateral line lobe of Gnathonemus, did not contain detectable amounts of dopamine. In spite of the high differentiation of the brain of Gnathonemus, the distribution of catecholamines as visualized with dopamine immunohistochemistry appears to be basically similar to that described in other teleostean and actinopterygian fishes on the basis of formaldehyde-induced fluorescence or tyrosine hydroxylase immunohistochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Distribution of serotonin in the brain of the mormyrid teleost Gnathonemus petersii.

The distribution of serotonin-immunoreactive neurons and fibers was studied in the highly developed brain of the weakly electric fish Gnathonemus petersii with the aid of specific antibodies against serotonin. Serotoninergic cell bodies occur in three regions: the raphe region of the brainstem, the hypothalamus, and the transition zone between the dorsal thalamus and the pretectum. Serotoninergic raphe neurons are clustered in three groups: nucleus raphes superior, intermedius, and inferior. The latter has not been described in other teleosts and thus might be the source of the serotoninergic innervation of specific mormyrid electrosensory brain regions. Most hypothalamic serotoninergic neurons have cerebrospinal-fluid (CSF)-contacting processes and thus belong to the paraventricular organ (PVO), which in Gnathonemus is located around a number of small infundibular recesses. The distribution of serotonin in the PVO precisely matches the distribution of dopamine, as described previously. Serotoninergic cells in the thalamopretectal transition zone also have been described in other teleosts, but not in other vertebrate groups, and thus seem to represent a teleostean specialization. Serotoninergic fiber density is especially high in the medial forebrain bundle and surrounding preoptic and hypothalamic regions as well as in several telencephalic and preoptic subependymal plexus. Serotoninergic fibers appear to be almost completely absent in the large and differentiated corpus and valvula cerebelli. Comparison with the literature on teleostean serotoninergic innervation patterns reveals several mormyrid specializations, including the absence of serotonin in large parts of the mormyrid telencephalic lobes, a differentiated innervation pattern of distinct electrosensory and mechanosensory subnuclei of the torus semicircularis, a refined serotoninergic lamination pattern in the midbrain tectum, and a prominent innervation of the electrosensory lateral line lobe, the associated caudal cerebellar lobe, and the electromotor medullary relay nucleus. A distinct innervation of several types of (pre)motor neurons, such as the Mauthner cells and facial motor neurons, has not been reported previously for other teleosts. Consequently, the distribution of serotoninergic fibers as well as neurons in the mormyrid brain is substantially adapted to the high degree of differentiation of its electrosensory and telencephalic brain regions, but serotoninergic innervation is not involved in the circuitry of the most impressive part of the mormyrid brain; i.e., its large corpus and valvula cerebelli.

Animals↗
PubMed1989

Differences in the fiber composition of the pyramidal tract in two- and 14-month-old rats.

The present study is aimed at an electron-microscopic morphometrical analysis of the pyramidal tract of 14-month-old rats at the level of the pyramis medullae and the second cervical segment, and a comparison with data obtained for rats of two months of age. Between 2 and 14 months of age there is, at the level of the pyramis medullae of the left pyramidal tract, a statistically significant increase of the number of myelinated fibers, from 91,000 to 118,000, whereas the total number of unmyelinated fibers decreases from 133,000 to 101,000. On the right side at the same level there is no statistically significant change in the number of myelinated fibers, whereas there is a significant decrease of unmyelinated fibers at this side, from 148,000 to 89,000. At the second cervical level, a statistically significant increase in the number of myelinated fibers has been noted at both sides (from 43,000 to 60,000) between 2 and 14 months, whereas the mean total number of unmyelinated fibers at this level decreases somewhat (from 35,000 to 28,000), but is not statistically significant. Several processes which might be involved in the age-related changes observed are discussed, including the possibility of a shift from unmyelinated fibers to myelinated ones, withdrawal of corticobulbar fibers and ongoing outgrowth of myelinated corticofugal fibers after two months of age, and a summarizing scheme is presented. We conclude that the pyramidal tract of the rat changes in composition after the age of two months and that continuing outgrowth of myelinated corticospinal fibers is an important aspect of this continuing development.

Aging↗
PubMed1989

Different requirements for formation of Jun: Jun and Jun: Fos complexes.

The cFos proto-oncoprotein associates with cJun to form a heterodimer with increased DNA binding and transcriptional activities. It has been suggested that dimerization of these proteins is mediated by the interdigitation of an orderly repeat of leucine residues forming a leucine zipper. In agreement with this model, we find that binding to the AP-1 site requires dimerization of these proteins. Although cFos, itself, does not seem to dimerize and bind to the AP-1 site, Jun: Fos heterodimers have higher stability than Jun homodimers, which accounts for their increased DNA binding activity. Mutational analysis indicates that at least three of the repeated leucines of cJun are important for homodimer formation. However, these residues can be mutated without affecting formation of Jun: Fos heterodimers. In addition, several other residues present between the leucines are also important for both homo- and heterodimerization. These findings provide support for the recent proposal that these proteins dimerize via formation of a coiled coil and suggest that residues other than leucines provide specificity for this interaction. Assuming that dimerization is required for proper alignment of the DNA recognition sites, we generated a cJun mutant containing a small insertion between the dimerization and the DNA recognition domains. This mutant fails to bind DNA, but it acts as a trans-dominant inhibitor of cJun and cFos because it still dimerizes with the wild-type proteins.

Alleles↗
PubMed1989

Jun and v-jun contain multiple regions that participate in transcriptional activation in an interdependent manner.

Transcription factor AP1 is a heteromeric complex composed of the Jun and Fos proteins. It has been shown that by associating with Jun, Fos increases Jun's ability to bind DNA and activate transcription. To determine the roles of the two proteins, we undertook the functional analysis described here. We show that both the cellular Jun and its viral counterpart, v-Jun, are efficient transcriptional activators even in the absence of Fos. The Jun proteins contain at least three separate regions responsible for transcriptional activation in F9 cells, which act in an additive manner. All of these regions contain several acidic amino acid residues that appear to be functionally important and interact with a titratable target. Although trans-activation by Fos was previously shown to be dependent on the presence of Jun, by fusing Fos to a heterologous DNA-binding domain we show that once given the ability to bind DNA on its own, Fos is also an independent trans-activator. Both Jun and Fos contribute to trans-activation by the AP1 complex, and the augmentation of Jun activity by Fos is probably due to the increased DNA-binding activity of the Jun:Fos heterodimer.

Amino Acid Sequence↗
PubMed1988

Morphometric parameters of the superior colliculus of albino and pigmented rats.

The superior colliculus (SC) or optic tectum of mammals consists of seven layers, numbered I-VII from superficial to deep, each of which has distinct connectivity patterns and electrophysiological response properties. The present study is devoted to a morphometrical analysis of neuronal diameters, densities, and numbers in different layers and regions of the SC of albino as well as pigmented rats in order to present a quantitative characterization of the collicular neuronal population involved in the different connectivities and functions of these compartments. The morphometric parameters were calculated from tracings of nuclei and cell bodies by means of Kontron-Videoplan equipment and a Micro PDP 11/23 computer. The mean soma diameter per superior colliculus appears to be 12.0 microns, the average neuronal density 70 cells per 0.001 mm3, and the total number of neurons about 600,000. The mean soma diameter gradually increases from superficial to deep layers (i.e., from 10.0 to 14.0 microns). Cellular density is highest in layer III, the retinal afferent layer (90 cells per 0.001 mm3), and decreases both in more superficial layers (to about 80 in layer I) and deeper layers (to about 44 in layer VII). About 25% of all collicular neurons are situated in layer II whereas layer I contains the lowest percentage of cells (4%). Rostrally within each collicular layer, cellular volumes are about 25% larger than caudally. On the other hand, neuronal densities are rostrally about 38% lower than caudally in all layers except for layers VI and VII. We conclude that collicular neurons, in contrast to collicular axons, are not arranged in distinct layers or clusters but basically establish a random network with only gradual transitions. In this respect, no statistically significant differences were observed between albino and pigmented rats.

Albinism↗
PubMed1988

The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes.

Cell lines stably transfected with metal inducible, MT-fos chimeric genes were used to study the ability of the c-fos gene product, Fos, to act as a transcriptional trans-activator. In 3T3MTfos cells, induction of Fos expression led to specific trans-activation of an AP-1 responsive reporter gene. Induction of Fos expression in F9MTfos cells, however, did not lead to trans-activation. Since, unlike NIH3T3 cells, F9 cells do not contain detectable levels of AP-1, we examined whether a c-Jun/AP-1 expression vector can restore the trans-activating effect of Fos in F9MTfos cells. Transfection with a functional c-Jun/AP-1 vector restored the specific trans-activating effect of Fos on AP-1 responsive constructs. When incubated with nondenatured cell extracts, anti-cFos antisera precipitated a protein complex composed of Fos and several Fos associated proteins (FAP). One of these, FAP p39, is structurally identical to c-Jun/AP-1. These results suggest that Fos is a trans-acting factor that is capable of stimulating gene expression not by direct binding to DNA but by interaction with the sequence-specific transcription factor AP-1. Therefore recognition of specific cis-elements by AP-1 is a prerequisite for Fos-mediated stimulation of gene expression.

Cell Line↗