Biomedical subjects

A Kossel

Publications and source records attributed to A Kossel.

12 recordsLinked to original sources

PubMed1999

Relative contribution of endogenous neurotrophins in hippocampal long-term potentiation.

Recent evidence has shown that brain-derived neurotrophic factor (BDNF) is involved in hippocampal long-term potentiation (LTP). Because the reagents used in acute experiments react not only with BDNF but also with neurotrophin-4/5 (NT4/5) and neurotrophin-3 (NT3), we examined the involvement of these neurotrophins in LTP using two highly specific, function-blocking monoclonal antibodies against BDNF and NT3, as well as a TrkB-IgG fusion protein. Our results show that NT3 antibodies did not have any effects on LTP. However, both TrkB-IgG fusion proteins and BDNF antibody similarly reduced LTP, suggesting that only BDNF but no other ligands of the TrkB-receptor are likely to be involved in LTP induction. The reduction in LTP depended on the inducing stimuli and was only observed with theta-burst stimulation (TBS) but not with tetanic stimulation. We further observed that LTP was only reduced if BDNF was blocked before and during TBS stimulation, and BDNF antibodies did not affect early or late stages of LTP if they were applied 10, 30, or 60 min after TBS stimulation. These results point toward a specific and unique role of endogenous BDNF but not of other neurotrophins in the process of TBS-induced hippocampal LTP. Additionally, they suggest that endogenous BDNF is required for a limited time period only shortly before or around LTP induction but not during the whole process of LTP.

Animals↗

PubMed1997

Area-specific regulation of gamma-aminobutyric acid type A receptor subtypes by thalamic afferents in developing rat neocortex.

Targeting and innervation of the cerebral cortex by thalamic afferents is a key event in the specification of cortical areas. The molecular targets of thalamic regulation, however, have remained elusive. We now demonstrate that thalamic afferents regulate the expression of gamma-aminobutyric acid type A (GABAA) receptors in developing rat neocortex, leading to the area-specific expression of receptor subtypes in the primary visual (V1) and somatosensory (S1) areas. Most strikingly, the alpha1- and alpha5-GABAA receptors exhibited a reciprocal expression pattern, which precisely reflected the distribution of thalamocortical afferents at postnatal day 7. Following unilateral lesions at the birth of the thalamic nuclei innervating V1 and S1 (lateral geniculate nucleus and ventrobasal complex, respectively), profound changes in subunit expression were detected 1 week later in the deprived cortical territories (layers III-IV of V1 and S1). The expression of the alpha1 subunit was strongly down-regulated in these layers to a level comparable to that in neighboring areas. Conversely, the alpha5 subunit was up-regulated and areal boundaries were no longer discernible in the lesioned hemisphere. Changes similar to the alpha5 subunit were also seen for the alpha2 and alpha3 subunits. These results indicate that the differential expression of GABAA receptor subtypes in developing neocortex is dependent on thalamic innervation, contributing to the emergence of functionally distinct areas.

Animals↗

PubMed1995

The specificity of interactions between the cortex and the thalamus.

The functioning of the adult mammalian cerebral cortex depends critically upon precise interconnections between specific thalamic nuclei and distinct cortical regions. Therefore, one central issue in understanding cortical development is determining the cellular and molecular strategies underlying the specification of thalamocortical projections. We address the role of axon-axon interactions and membrane-bound guidance molecules in the establishment of the development of layer-specific patterns of afferent and efferent cortical connections does not depend upon neuronal activity. We present evidence that activity conveyed by thalamic afferents is required for the elaboration of the columnar specificity of cortical circuits.

Animals↗

PubMed1995

Relationships between dendritic fields and functional architecture in striate cortex of normal and visually deprived cats.

We examined relationships between the pattern of geniculocortical innervation and the dendritic fields of cells in layer 4 of in cat primary visual cortex. Experiments were performed on normal animals and on cats in which the geniculocortical projection was altered by monocular deprivation or by the induction of divergent squint during the critical period. Thalamic afferents providing the input from the contralateral eye were anterogradely labeled by injecting the fluorescent tracer Dil into lamina A of the lateral geniculate nucleus. Intracellular staining with Lucifer yellow in slice preparations allowed simultaneous visualization of the morphology of individual cells and the thalamic afferents. Our results demonstrate that spiny stellate cells close to the upper and lower margin of the geniculocortical input have highly asymmetric dendritic fields, and thereby confine their dendrites to the termination zone of these afferents. This effect was specific for the cell class; it was not observed in pyramidal neurons. These dendritic asymmetries perpendicular to the laminar borders of spiny stellate cells were not altered by monocular deprivation or strabismus. In contrast, visual deprivation strongly influenced the dendritic arbors of spiny stellate cells near the borders between adjacent ocular dominance columns. In normal animals, the dendrites of cells near columnar borders remained preferentially within one column. These dendritic asymmetries became much more pronounced in strabismic animals. Monocular deprivation weakened the influence of the columnar borders on dendritic fields. Spiny stellate cells within the columns of the open eye exhibited a slight tendency to confine their dendrites to these columns. Cells in the columns of the deprived eye showed the opposite effect; they extended their dendrites preferentially into the adjacent columns of the open eye. These results demonstrate that the segregation of geniculocortical afferents into ocular dominance columns and its perturbation by manipulation of the visual input plays an important role in defining the morphology of cortical target cells. Thus, activity-dependent structural changes not only occur at the level of the presynaptic terminals, but also at the level of the postsynaptic target cells, and thereby contribute to build up the functional architecture of the cortex.

Animals↗

PubMed1990

Effects of NMDA antagonists on developmental plasticity in kitten visual cortex.

The existence of Hebb synapses in the visual cortex of young kittens has long been postulated. A mechanism for the correlation of activity in simultaneously active pre- and postsynaptic neurons could be provided by the properties of the N-methyl-D-aspartate (NMDA) receptor and its associated Ca2+ channel, which opens in a transmitter- and voltage-dependent manner. We have studied the effects on cortical plasticity of blocking NMDA receptors in different ways with competitive and non-competitive NMDA antagonists. In our first approach, the non-competitive NMDA antagonist ketamine, a short-acting dissociative anaesthetic, was injected systemically after each of a series of brief monocular exposures. This procedure prevented the development of an ocular dominance shift towards the experienced eye in the visual cortex. Other short-acting anaesthetics, such as xylazine or methohexital, while providing the same depth of anaesthesia, did not have the same effect on ocular dominance plasticity. We conclude, therefore, that ketamine quite specifically interferes with synaptic consolidation in the visual cortex. In order to establish a role of NMDA receptors for cortical plasticity directly in the visual cortex, we performed another series of experiments: 2-amino-5-phosphono-valerate (APV), a competitive NMDA antagonist, was infused intracortically by means of implanted osmotic minipumps in kittens, which were monocularly deprived for 1-2 weeks. Within a radius of 4-5 mm, the expected ocular dominance shift was prevented or reduced. In addition, however, physiologically determined cell density and responsiveness to visual stimuli were grossly abnormal around the infusion site, and histological cell density was also reduced. Similar effects were found when MK801 (a non-competitive NMDA antagonist) was used in the same type of experiment. The outcome of both experimental approaches makes it very likely that NMDA antagonists somehow interfere with cortical plasticity. Their mode of action, however, remains ambiguous. Although it is quite possible that blocking of the NMDA channel prevents the Hebbian correlative process necessary for synaptic consolidation, more complex effects, such as an interference with a neurotrophic action normally exerted via the NMDA receptor, may have to be taken into account as well.

2-Amino-5-phosphonovalerate↗

PubMed1990

Non-Hebbian synapses in rat visual cortex.

In the mammalian CNS, long term potentiation can be induced by repeatedly pairing presynaptic stimulation with postsynaptic depolarization of a single cell, similar to a model proposed by Hebb, that synaptic strengthening occurs as a result of correlated pre- and postsynaptic activity. However, our experiments indicate that the Hebbian rule is not strictly valid in the cortex. Double intracellular recordings showed that synaptic reinforcement is not confined to the depolarized postsynaptic neuron, but is also observed in adjacent but not coactivated neurons. The enhancement and its spread is stimulus-specific, it occurs only for fibres stimulated during the pairing procedure. During development, this spread might lead to a characteristic organizing principle of the cortex, the clustering of cells with similar functional properties.

Animals↗

PubMed1990