PubMed Health⌕ Search

Biomedical subjects

C M Müller

Publications and source records attributed to C M Müller.

At least 37 records · Page 2Linked to original sources
PubMed1993

Glial cell functions and activity-dependent plasticity of the mammalian visual cortex.

The presence of highly ordered connectivities is one basic characteristic of the central nervous systems and is believed to be a prerequisite for its proper function. The elaboration of precise, topographic projections has been shown to include two subsequent steps: (1) The formation of exuberant projections with limited topographic accuracy, and (2) the activity-dependent refinement of the appropriate connectivities by synapse elimination and synapse stabilization. Although most current theories on the mechanisms underlying activity-dependent developmental plasticity focus on adaptive changes of the efficacy of synaptic transmission, the present overview deals with possible mechanisms underlying morphologic adaptations in the developing central nervous system. Especially the contribution of glial cells in the activity-dependent selection of neuronal projections in the thalamocortical visual system of higher mammals is elaborated and a unifying hypothesis on the involvement of nonneuronal cells in neuronal plasticity is formulated on the basis of the current knowledge on glial physiology and specific experimental data.

Animals↗
PubMed1992

Astrocytes in cat visual cortex studied by GFAP and S-100 immunocytochemistry during postnatal development.

A monoclonal antibody to glial fibrillary acidic protein (GFAP) and a polyclonal antiserum to the S-100 protein were used to study the expression of these astrocytic proteins in the postnatal visual cortex of the cat. Three changes in antigen expression of these astroglial markers could be distinguished over development. First, the density of cells in the white matter, which are heavily labelled with both antibodies from birth until adulthood, diminishes after the third postnatal weeks. By intracellular filling with Lucifer Yellow the reduction of the cell density can be attributed to the disappearance of large astrocytes with a morphology of transforming radial glia, present only in early postnatal development. Second, heavily labelled, large cells present in the grey matter at the seventh postnatal day have disappeared by the fifth postnatal week. On the basis of their morphology these cells can also be classified as radial glial cells. Finally, astroglial cells of the adult-like stellate form appear to be labelled in the cortical layers between the third and seventh postnatal weeks. While the density of these cells and the S-100 immunoreactivity of the cell bodies is adult-like at the fourth postnatal week, there is a gradual increase of the staining intensity with the GFAP antibody up to the seventh postnatal week. This developmental period is paralleled by the appearance of S-100-positive astrocytic processes. The gradual expression of GFAP immunoreactivity and the increased expression of S-100 is interpreted as reflecting the time course of astrocytic maturation. A possible relation of the maturation of astrocytes and cortical development, both of which are prominent in the time period between the third and seventh postnatal week, is discussed.

Aging↗
PubMed1992

Postnatal development of dye-coupling among astrocytes in rat visual cortex.

Intercellular coupling among astrocytes was studied in rat visual cortex slices from animals aged 1 week to 4 months. Cell coupling via gap junctions was determined by the dye spread of the low molecular weight dye Lucifer Yellow CH injected into electrophysiologically identified cells to adjacent cells. Coupling among glial cells was first detected at postnatal day 11 and was thereafter consistently observed until adulthood. Dye spread was observed up to 300 microns radially from the injected cell covering multiple cortical layers. Following dye injection into a single cell up to several hundred Lucifer Yellow-positive cells could be observed. Quantitative analysis revealed a similar extent of dye spread at different developmental stages including a quite constant number of dye-coupled astrocytes from the end of the second postnatal week to adulthood. Double labelling of Lucifer Yellow-filled cells with an antiserum against the glial fibrillary acidic protein confirmed the astrocytic nature of the injected and coupled cells. Comparison of the density of dye-coupled cells in a given area and the total number of astrocytes as revealed by immunocytochemical staining suggests that dye-coupling includes the entire local astrocytic population. It is concluded that coupling among astrocytes via gap junctions in rat visual cortex occurs shortly after birth and reflects one of the first steps in astroglial maturation.

Animals↗
PubMed1992

A role for glial cells in activity-dependent central nervous plasticity? Review and hypothesis.

Activity-dependent plasticity relies on changes in neuronal transmission that are controlled by coincidence or noncoincidence of presynaptic and postsynaptic activity. These changes may rely on modulation of neural transmission or on structural changes in neuronal circuitry. The present overview summarizes experimental data that support the involvement of glial cells in central nervous activity-dependent plasticity. A role for glial cells in plastic changes of synaptic transmission may be based on modulation of transmitter uptake or on regulation of the extracellular ion composition. Both mechanisms can be initiated via neuronal-glial information transfer by potassium ions, transmitters, or other diffusible factor originating from active neurons. In addition, the importance of changes in neuronal circuitry in many model systems of activity-dependent plasticity is summarized. Structural changes in neuronal connectivity can be influenced or mediated by glial cells via release of growth or growth permissive factors on neuronal activation, and by active displacement and subsequent elimination of axonal boutons. A unifying hypothesis that integrates these possibilities into a model of activity-dependent plasticity is proposed. In this model glial cells interact with neurons to establish plastic changes; while glial cells have a global effect on plasticity, neuronal mechanisms underlie the induction and local specificity of the plastic change. The proposed hypothesis not only explains conventional findings on activity-dependent plastic changes, but offers an intriguing possibility to explain several paradoxical findings from studies on CNS plasticity that are not yet fully understood. Although the accumulated data seem to support the proposed role for glial cells in plasticity, it has to be emphasized that several steps in the proposed cascades of events require further detailed investigation, and several "missing links" have to be addressed by experimental work. Because of the increasing evidence for glial heterogeneity (for review see Wilkin et al., 1990) it seems to be of great importance to relate findings on glial populations to the developmental stage and topographical origin of the studied cells. The present overview is intended to serve as a guideline for future studies and to expand the view of "neuro" physiologists interested in activity-dependent plasticity. Key questions that have to be addressed relate to the mechanisms of release of growth and growth-permissive factors from glial cells and neuronal-glial information transfer. It is said that every complex problem has a simple, logical, wrong solution. Future studies will reveal the contribution of the proposed simple and logical solution to the understanding of central nervous plasticity.

Adaptation, Physiological↗
PubMed1991

Distribution of glial fibrillary acidic protein and vimentin immunoreactivity during rat visual cortex development.

The postnatal maturation of astrocytes in the rat visual cortex was analysed by immunostaining the astroglial proteins vimentin and glial fibrillary acidic protein with poly- and monoclonal antibodies. Vimentin immunoreactivity was present in the visual cortex up to the third postnatal week, whereas immunolabelling first disappeared in the cortical layers and then in the white matter. In the early postnatal period, vimentin antibodies labelled radial glial fibres. After the first postnatal week staining of radial glial fibres gradually disappeared and vimentin immunoreactivity was localized in a few protoplasmic astrocytes in the grey matter and fibrous astrocytes in the white matter. The development of glial fibrillary acidic protein-positive astrocytes was not fully complete until postnatal day 50. Glial fibrillary acidic protein-positive radial glial fibres were present after birth and disappeared towards the end of the third postnatal week. Staining of astrocytes in the white matter and in cortical layers I and VI reached an adult density at postnatal days 8 and 20, respectively. A progressively later development of glial fibrillary acidic protein-positive astrocytes was observed in cortical layers II-V which was completed between postnatal days 47 and 50. In the adult rat visual cortex glial fibrillary acidic protein-positive astrocytes were especially dense in layers I and VI, moderate in layers II/III and V and nearly absent in layer IV and lower layer III. The time course of the loss of vimentin and the gradual appearance of glial fibrillary acidic protein immunoreactivity in the visual cortex is considered as an index of astrocytic maturation and the spatiotemporal sequence of this maturation pattern is discussed in terms of reciprocal neuron-astrocyte interactions during brain development.

Animals↗
PubMed1990

Dark-rearing retards the maturation of astrocytes in restricted layers of cat visual cortex.

The cat visual cortex develops its mature appearance, i.e., its circuitry and neuronal morphology, during a limited period of postnatal development under the influence of visual experience. The critical period for cortical plasticity, which normally extends from the third to seventh postnatal week, can be prolonged by raising animals in total darkness. The prolongation of the critical period by dark-rearing is restricted to the cortical layers except layer IV. Besides the influence of afferent activity on the physiology of cortical cells and on the interconnectivity of thalamo-cortical afferents, visual experience has also been shown to affect the development of glial cells. The present study investigates the effects of dark-rearing on astroglial characteristics as determined by immunostaining for glial fibrillary acidic protein (GFAP) and the S-100 protein. The data reveal a retardation of astrocytic maturation in dark-reared animals, shown by a reduced presence of GFAP immunoreactivity compared to light-experienced animals. The density of astrocytic cell bodies positive for S-100 is unaffected by dark-rearing, suggesting that astroglial proliferation does not rely on afferent activity. However, punctate S-100 staining in the neuropil, which has been shown to reflect astrocytic processes, was also reduced in certain cortical layers in dark-reared animals. The effects of dark-rearing on the expression of GFAP and S-100 were restricted to the cortical layers except layer IV, i.e., those layers that reveal a prolongation of the critical period for cortical plasticity following dark-rearing. It is concluded that astrocytic maturation in the visual cortex is influenced by neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ocular dominance plasticity in adult cat visual cortex after transplantation of cultured astrocytes.

During a critical restricted period of postnatal development, the visual cortical circuitry is susceptible to modifications that are dependent on experience. If vision is restricted to only one eye during this period, the territories innervated by the deprived eye shrink considerably, whereas those innervated by the non-deprived eye expand, and the deprived eye loses the ability to influence almost all of the cells in the cortex. Thus, changes in ocular dominance are paralleled and possibly mediated by synapse elimination and axonal sprouting. Hypotheses about the mechanisms underlying ocular-dominance plasticity assume the activation of NMDA (N-methyl-D-aspartate) receptors and subsequent calcium influx as a trigger of synaptic modifications. In addition, plasticity relies on functional neuromodulatory afferents. On the basis of immunocytochemical studies, it was recently proposed that the presence of immature astrocytes is a prerequisite for visual cortical plasticity, and that the end of the critical period is causally linked to the maturation of astrocytes. Here we report, in support of this hypothesis, that resupplementation of the visual cortex of adult cats with astrocytes cultured from the visual cortex of newborn kittens reinduces ocular-dominance plasticity in adult animals.

Animals↗
PubMed1989

Acetylcholine-induced inhibition in the cat visual cortex is mediated by a GABAergic mechanism.

The influence of iontophoretically applied acetylcholine (ACh) on single-unit activity in the visual cortex was studied in anesthetized cats. The dominant effect consisted of a slow facilitation of neuronal responses to moving light bars. This cholinergic action was sometimes paralleled by a decrease of the cells' selectivity to the direction of stimulus movement. In about one-third of the neurons studied ACh-iontophoresis suppressed maintained and visually driven activity within a few hundred milliseconds from the onset of its application. This effect was antagonized by concurrent iontophoresis of the muscarinic ACh-receptor antagonist scopolamine and the GABAA-receptor antagonist bicuculline methiodide. In 7% of the units studied a fast excitation was elicited by ACh application showing a similar time course as the rapid suppressive effect. It is concluded that ACh-induced inhibition is mediated by an activation of GABAergic interneurons. The role of cholinergic depression and facilitation in cortical information processing is discussed.

Acetylcholine↗
PubMed1989

Postnatal development of vimentin-immunoreactive radial glial cells in the primary visual cortex of the cat.

In kitten area 17 vimentin-like immunoreactivity is expressed in radial glial fibres up to one month postnatally, i.e. the time for which neuronal migration continues. During this time fibre density gradually decreases. A subpopulation of these fibres also contains S-100 protein and glial fibrillary acidic protein. However, these latter antigens disappear earlier than vimentin. In addition, vimentin immunoreactivity can be observed in astroglial cells of the white matter between the second and fifth postnatal week. Many of these cells resemble mature astrocytes but partially they have an intermediate morphology suggesting the possibility that they originated from radial glia. Such displaced radial glial cells' are also positive for S-100 protein both in the cortex and white matter. Thus it is conceivable that at least part of the astrocytes of mature cat visual cortex originate from vimentin- or S-100-immunoreactive radial glia.

Animals↗
PubMed1988

Distribution of GABAergic perikarya and terminals in the centers of the higher auditory pathway of the chicken.

The distribution of presumed GABAergic neurons and axon terminals in nuclei of the higher auditory pathway of the chicken was investigated by immunocyto-chemical methods employing antisera to the rate-limiting enzyme of GABA synthesis, glutamic acid decarboxylase, and to GABA. In the mesencephalic auditory center (MLD) about 20% of the cells reveal immunoreactivity. In contrast, the thalamic relay station nucleus ovoidalis is devoid of immunostained somata. This nucleus contains a high density of punctate immunoreactive structures presumed to be GABAergic axon terminals. In the auditory forebrain center field L and the auditory portions of the hyperstriatum ventrale, up to 8% of the cells were immunopositive. These neurons were significantly smaller than estimated from measurements of the overall cell population in these nuclei. From the two-dimensional arrangement of immunopositive neurons it is suggested that the GABAergic system in the avian auditory telencephalon consists of two separate groups of neurons: one subgroup mediating local inhibitory interactions, the other responsible for lateral inhibition between different frequency representations.

Animals↗
PubMed1988

Contribution of GABAergic inhibition to the response characteristics of auditory units in the avian forebrain.

1. We tested the contribution of GABAergic inhibition to the response characteristics of 213 neurons in the auditory telencephalon of chronically prepared nonanesthetized chickens. Extracellular recordings were obtained with multibarrel glass electrodes containing a tungsten wire. Auditory stimuli consisted of tones, two-tone combinations, and noise bursts presented either free field or via earphones. 2. Response properties of the neurons were studied both before and during iontophoretic application of GABA, glutamate, bicuculline methiodide (BIC), and acetylcholine. 3. During BIC application excitatory responses were facilitated. With the exception of transient off-responses, which occasionally appeared only in the BIC condition, the temporal response patterns to tone stimuli at the units' best frequency usually were unaltered. In no case was an inhibitory response component to binaurally presented pure tones antagonized by BIC. 4. BIC iontophoresis enlarged the isointensity-response areas of the vast majority of neurons in the structures of the auditory forebrain lying postsynaptic to the thalamorecipient layer L2. This effect was not obtained when neurons were depolarized to perithreshold levels with glutamate. 5. Two-tone stimulation resulted in a suppression of the excitatory response to a neuron's best frequency when the second frequency lay outside the excitatory response area. In lamina L2, the frequency range inducing two-tone suppression was narrow, and the suppressive effect was not antagonized by BIC. In the postsynaptic layers, frequencies up to three octaves from the neurons' best frequency induced two-tone suppression that was sensitive to BIC. In addition, these neurons also displayed a BIC-insensitive suppression similar to the one seen in layer L2. 6. Neurons displaying no or only a poor response to white-noise stimulation strongly responded to this wide-band stimulus during BIC iontophoresis. 7. Neurons without tone responses usually displayed clear response areas to tones during BIC application. Iontophoretic application of acetylcholine, but not glutamate, also induced such tone responses. Two-tone combinations with frequencies lying within the response areas observed in the BIC condition elicited excitatory responses after full recovery from the BIC application. 8. During BIC iontophoresis nonmonotonic intensity-response functions were converted to monotonic functions in most of the neurons studied. 9. A model of GABAergic inhibitory interactions is proposed that is based on two independent GABAergic systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1988

Cholinergic mechanisms in the reticular control of transmission in the cat lateral geniculate nucleus.

1. We examined the hypothesis that the ascending reticular arousal system influences thalamic transmission through a cholinergic mechanism. Extra- and intracellular recordings were obtained from neurons of the dorsal lateral geniculate nucleus (LGNd) and the perigeniculate nucleus (PGN) of cats anesthetized either with N2O and pentobarbital or with N2O and halothane. We compared the effects that electrical stimulation of the mesencephalic reticular formation (MRF) and ionophoretically applied acetylcholine (ACh) have on spontaneous and evoked activity of individual neurons and tested whether these effects could be antagonized by ionophoretic administration of the muscarinic receptor blocker scopolamine. The effects of ionophoretically applied glutamate (GLU), N-methyl-D-aspartate, and bicuculline were examined in addition. 2. The prominent effects in LGNd relay cells of both ACh application and of MRF stimulation were an enhancement of the resting discharge, a facilitation of the excitatory responses to light, a reduction of the amplitude and duration of evoked inhibitory episodes, and a blockade of postinhibitory rebound burst. These latter effects resembled those induced with bicuculline. Under barbiturate anesthesia neither ACh application nor MRF stimulation elicited discharges when the excitatory input from the retina was blocked. Ionophoretic application of hte muscarinic antagonist scopolamine abolished the effects of ACh ionophoresis in all relay cells tested (n = 20), and in 10 cells it also antagonized completely the effects of MRF stimulation. In the remaining cells scopolamine reduced the effects of MRF stimulation. 3. Increasing the depth of anesthesia reduced or abolished the effects of ACh application and MRF stimulation on the cells' resting activity but did not interfere with the facilitation of evoked responses. 4. The effects of the excitatory amino acids GLU and NMDA differed from those of MRF stimulation and ACh application, since the former always enhanced both spontaneous and evoked discharges but neither shortened phases of evoked inhibition nor abolished postinhibitory rebound bursts. 5. There was a high correlation between the effectiveness of MRF stimulation and ACh application in individual neurons. On the average, the facilitation of evoked responses was more pronounced in X- than in Y-cells, and the fraction of cells responding with an increase of resting activity to both procedures was considerably higher among X- than among Y-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1987

GABAergic inhibition increases the neuronal selectivity to natural sounds in the avian auditory forebrain.

The influence of the iontophoretically applied GABA antagonist bicuculline-methiodide (BIC) on single cell selectivity to natural sounds in the auditory forebrain was studied in awake chickens. Units in the thalamo-recipient lamina showed no clear changes in neuronal selectivity during BIC application, while cells postsynaptic to this layer displayed a clear loss of response selectivity. The results are discussed in regard to the role of GABA-mediated inhibition in auditory processing within the telencephalon.

Acoustic Stimulation↗
PubMed1987

gamma-Aminobutyric acid immunoreactivity in brainstem auditory nuclei of the chicken.

Using an antiserum directed against gamma-aminobutyric acid (GABA), the presence of presumed GABAergic neurons is demonstrated in the chicken auditory brainstem nuclei: nucleus laminaris, nucleus angularis, superior olive, and the ventral nuclei of the lateral lemniscus. Nucleus magnocellularis contains no immunopositive neurons but numerous GABA-positive terminals surrounding the cells. Terminal labeling is also present in the other auditory nuclei, though scarcer and not always associated with cell bodies. These data suggest an involvement of GABAergic inhibition in auditory processing in the lower auditory pathway of birds.

Animals↗