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M Kossut

Publications and source records attributed to M Kossut.

At least 19 recordsLinked to original sources

Delayed upregulation of GABA(A) alpha1 receptor subunit mRNA in somatosensory cortex of mice following learning-dependent plasticity of cortical representations.

Experience-dependent modifications of cortical representational maps are accompanied by changes in several components of GABAergic inhibitory neurotransmission system. We examined with in situ hybridization to 35S-labeled oligoprobe changes of expression of GABA(A) receptor alpha1 subunit mRNA in the barrel cortex of mice after sensory conditioning training. One day and 5 days after the end of short lasting (3 daily sessions) training an increased expression of GABA(A) alpha1 mRNA was observed at the cortical site where the plastic changes were previously found. Learning associated activation of the cerebral cortex increases expression of GABA(A) receptor mRNA after a short post-training delays.

Animals↗

PSD95 protein level rises in murine somatosensory cortex after sensory training.

Proteins of the postsynaptic density are implicated in mechanisms of synaptic plasticity. We examined involvement of PSD95 and alphaCaMkII in learning-dependent plastic changes of representational maps in somatosensory cortex of mice. The barrel cortex of mice was examined following a 3 day long classical conditioning training, in which activation of facial vibrissae was linked to an aversive stimulus. This procedure produced expansion of cortical representations of vibrissae involved in the training. In subcellular fraction enriched in postsynaptic densities from the barrel cortex, it was estimated by Western blotting that the level of PSD95 increased after the training by about 50%, while the level of CaMkII remained unchanged. The results indicate involvement of PSD95 in learning-dependent cortical plasticity.

Afferent Pathways↗

Rapid regulation of GAD67 mRNA and protein level in cortical neurons after sensory learning.

Cortical representations of different modalities can be modified by sensory learning. Our previous studies in the barrel cortex showed that expansion of the cortical representation of a row of vibrissae could be induced by pairing stimulation of a row of vibrissae with a tail shock. The plastic change in cortical reactivity to the input used during the training was accompanied by increased density of GABA immunoreactive neurons in the involved row of cortical barrels. Using the same paradigm, the present study examined the pathway of GABA synthesis-expression of GAD67 mRNA and immunoreactivity of GAD67 isoenzyme in the barrel cortex of mice after sensory learning. In situ hybridization revealed that the GAD67 mRNA level was elevated in one row of barrels in the trained group as well as in controls receiving vibrissae stimulation alone. In contrast, elevation of immunoreactivity of the GAD67 protein occurred only in the trained group. The density of GABA-immunoreactive neurons in the hollows of barrels representing the row of vibrissae activated during the training was increased by 50%. These data indicated that sensory stimulation alone affected expression of the 67 kDa glutamate decarboxylase isoenzyme synthesis pathway, whereas the processes involved in cortical plasticity induced by associative learning modified this pathway additionally at the level of translation.

Animals↗

Mice can learn roughness discrimination with vibrissae in a jump stand apparatus.

An adaptation of roughness discrimination task successfully used on rats was performed on mice. It was found that mice can master discrimination of rough surfaces using only mystacial vibrissae. This task can be used for studying sensory abilities of genetically modified mice as well as dynamics and pharmacology of complex sensory learning.

Animals↗

Age-dependent response of the mouse barrel cortex to sensory deprivation: a 2-deoxyglucose study.

The effect of age on the plastic response of vibrissal barrel cortex to deprivation was examined in adolescent (1 month at the start of the procedure, 2 months at testing) and mature (10- to 11-month-old) mice. A single vibrissa was plucked out for 3 weeks and allowed to regrow for 10 days; it was previously found that this deprivation paradigm induces strong downregulation of the deprived input. The results of deprivation were assessed with 2-deoxyglucose functional brain-mapping autoradiography. Deprivation was found to reduce the ability of the deprived vibrissa to activate the cortex both in adolescent and mature mice. However, while in young animals the decrease of the extent of cortical labeling, compared with the normal control, was observed in all examined cortical layers (II/III, IV, and V), in older mice the effect was reduced in layers II/III and absent in layer IV. The suppression of response of the infragranular layers was not affected by age. Transition from adolescent to mature adulthood brings about a layer-specific decline in depression of the cortical response to the deprived input.

Aging↗

GABA immunoreactivity in mouse barrel field after aversive and appetitive classical conditioning training involving facial vibrissae.

We have previously reported that a classical conditioning paradigm involving stimulation of a row of facial vibrissae produced an expansion of the cortical representation of the "trained row", labeled with 2-deoxyglucose (2DG), in layer IV of the barrel field. The present study has examined the pattern of GABA immunoreactivity (GABA-IR) in the cortical representation of row B of the facial vibrissae after (i) 3 days of aversive training, and (ii) 2 months of appetitive training, where stimulation of row B of vibrissae on one side of the snout was used as a conditioned stimulus. The most notable observation was a greater density of GABA-IR cells concentrated in the hollows of the "trained row" B barrels compared to the hollows in the barrel field of the opposite hemisphere in the same mouse. After aversive training, we noted a 2-fold increase in the density of GABA-IR neurons in the hollows of row B; after reward training, the increase amounted to 49%. In contrast, GABA-IR was unchanged in the control groups, which received only stimulation of vibrissae without the unconditioned stimulus. The classification of labeled neurons according to size revealed that the increase in density of GABA-IR neurons was confined to the small (12-15 microm) diameter group. We concluded that the GABAergic system undergoes up-regulation, after both associative learning paradigms, and that the population of small, GABAergic neurons plays an active role in use-dependent plasticity.

Animals↗

Deafferentation induced changes in GAD67 and GluR2 mRNA expression in mouse somatosensory cortex.

Partial vibrissectomy in adult mice induces body map plasticity in SI barrel cortex. To examine if the disturbed balance of cortical activation affects the excitatory and inhibitory neurotransmitter systems, we studied glutamic acid decarboxylase (GAD 67) and AMPA receptor subunit GluR2 mRNA expression in the barrel cortex. At varying times post-vibrissectomy, sparing row C of whiskers on one side of the snout, the brains were processed for in situ hybridization using specific [(35)S]oligonucleotides to detect the laminar localization of GAD67 and GluR2 mRNAs. Three and seven days after vibrissectomy, the expression of GAD67 was decreased in the deafferented cortex, while 30 days post-lesion, no effects were observed. At 3 days post-lesion, an ipsilateral decrease in GAD67 mRNA expression was also observed. No decreases in GluR2 transcripts were found in the deafferented cortex, but an increased expression was observed in the representation of the spared row C of whiskers 3 days after vibrissectomy. Seven and 30 days post lesion no changes in GluR2 expression were found. These data indicate that in the barrel cortex, peripheral deafferentation transiently regulates GAD67 and GluR2 expression at the transcriptional level. We suggest that this may be a manifestation of adaptive processes.

Afferent Pathways↗

Anatomical correlates of representational map reorganization induced by partial vibrissectomy in the barrel cortex of adult mice.

We examined the potential for changes in cortical connectivity to accompany long-term plastic changes in functional cortical representations of mystacial vibrissae. Plasticity in the barrel cortex of young adult mice was evoked by vibrissectomy that spared row C of whiskers. We found that 2-deoxyglucose brain mapping causes a progressive expansion of cortical representation of the spared vibrissae. Two months after vibrissectomy, when the width of the cortical map of the spared row of vibrissae doubled, living cortical slices of the barrel cortex were injected with fluorescent dextrans. The injections were centered on spared, deprived and control vibrissal columns. The injections labeled three intracortical projection systems: (i) local connections from one vibrissal column to neighboring columns; (ii) long-range projections running in the septa and walls of the barrels and spanning several barrels; and (iii) very-long-range fibers running horizontally in the lower part of layer V. The local, short-range projection system was analysed following small injections into the centers of columns in layers III and IV. We found that injections into spared barrels labeled axons extending for significantly greater distances in all layers (except layer V), and labeled cell bodies situated significantly further, than after injections into deprived or control barrels. Also, the total axonal density labeled by injections into the spared barrel was higher by 70% than for the deprived or control barrels. Alterations of topographical maps in adult somatosensory cortex may occur immediately after functional denervation, but may also increase with time, as in the case of our experimental situation. Our results indicate that persistent, long-term plastic change can remodel connectivity in the barrel cortex.

Animals↗

Learning-induced expansion of cortical maps--what happens to adjacent cortical representations?

The present study was designed to investigate the effects of learning-dependent enlargement of cortical representation of a row of vibrissae upon the appearance of adjacent cortical representations. We have found previously that three sessions of classical conditioning, during which stimulation of row B of vibrissae is paired with a tail shock, result in an increase of cortical representation of the trained row, as visualized with 2-deoxyglucose (2DG) metabolic functional mapping. In the present experiment, after the training in which row B was stimulated, we mapped with 2DG the cortical representations of rows A and C, not stimulated during the training. We found that these representations do not differ from normal. Because of expansion of cortical representation of the trained row, the overlap between representations of neighboring rows of vibrissae became greater and the two maps co-existed within the same cortical space.

Animals↗

Development of laminar distributions of kainate receptors in the somatosensory cortex of mice.

Kainate receptors were present at birth in the murine somatosensory cortex as revealed by quantitative in vitro autoradiography. During the first five postnatal days [3H]kainate binding rapidly increased and the maximum density in layer IV was reached at P12. The adult laminar pattern of receptor binding distribution was established by the third postnatal week with the heaviest labeling of infragranular layers. The sharp increase of kainate receptor during the first postnatal week coincides with the critical period for cytoarchitectonic plasticity of the barrels and establishment of functional thalamo-cortical connections in the barrel field.

Animals↗

Experience-dependent changes in function and anatomy of adult barrel cortex.

Manipulations of sensory input to vibrissal mechanoreceptors can modify columnar functioning of the barrel cortex in adult animals. In mice, partial vibrissectomy sparing one row of vibrissae in young adults results 7 days later in an increase in the functional cortical column activated by the spared whiskers and visualized with 2-deoxyglucose autoradiography. The increase in the extent of the labelled area is visible in all cortical layers, but particularly in layer V, where the metabolic labelling is more intense in the representation of the spared vibrissae. Two months after vibrissectomy the enlargement of the labelled area is accentuated. Deprivation of a row of vibrissae results in a decrease in the areal extent of its cortical representation. Investigations of cortico-cortical connections carried out in living slices of the barrel cortex of mice 2 months after vibrissectomy sparing one row of whiskers, revealed elongation and increased branching of axons originating in the spared cortical column. The dendritic spine density was increased on the basal dendrites of layer V pyramidal neurons of the spared column and decreased on layer III apical dendrites of the deprived column. Thus, prolonged changes in functional activation of adult barrel cortex are accompanied by rearrangement of cortico-cortical circuitry.

Adaptation, Physiological↗

Neonatal serotonin depletion modifies development but not plasticity in rat barrel cortex.

Effects of serotonin depletion (induced by neonatal injection of 5,7-dihydroxytryptamine) upon dimensions of cortical barrels and their metabolic activation, and upon effects of neonatal vibrissectomy sparing row C, were examined in 1-month-old rats. Dimensions of row C barrels, and of [14C]2-deoxyglucose (2-DG) labelling in the cortex obtained after stimulation of the row C vibrissae, were measured. Serotonin depletion did not change dimensions of barrels, but reduced the extent of 2-DG labelling of cortical representation of the row C whiskers by 30%. Vibrissectomy sparing this row resulted in an expansion of the row C barrels and of 2-DG labelling in the barrel cortex that were similar in both control and serotonin-depleted rats.

5,7-Dihydroxytryptamine↗

Glutamate receptors in cortical plasticity: molecular and cellular biology.

Glutamate receptors (GluRs) provide the major excitatory input to cortical neurons. Four main subtypes of GluRs are distinguished, namely, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and metabotropic receptors. All of them have been implicated in neuronal plasticity, and this paper reviews data that may be pertinent to the role played by GluRs in neocortical plasticity both in adult animals as well as during postnatal development. Emphasis is given to receptor distribution analyzed by various means, such as physiological responses, ligand binding as revealed by receptor autoradiography, and expression of receptor subunits at both mRNA and protein (immunoreactivity) levels. Possible mechanisms of involvement of GluRs in plastic changes on cortical neuron response are reviewed, and data on up- and downregulation of GluRs in neocortical plasticity are summarized. Functional studies involving either activation or blocking, and effects of such manipulation on cortical plasticity are discussed.

Animals↗

Transient increase of AMPA and NMDA receptor binding in the barrel cortex of mice after tactile stimulation.

The effects of sensory stimulation and sensory conditioning upon [3H]MK-801 [(+)-5-methyl-10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5, 10-imine] binding to N-methyl- d-aspartate (NMDA) receptor sites and [3H]AMPA (alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid) binding to AMPA receptor sites were examined in the primary somatosensory (SI) cortex of mice. Following short-lasting unilateral tactile stimulation of a selected row of vibrissae, and tactile stimulation paired with noxious stimulus (the pairing procedure was found to alter cortical representation of vibrissae), in vitro receptor binding autoradiography was performed on the sections of the barrel cortex of mice. One hour after the end of tactile stimulation or training procedure there was an increase of [3H]MK-801 and [3H]AMPA binding in the corresponding row of barrels in layer IV of the SI cortex of adult mice. These effects disappeared 24 h after the end of each experimental procedure. The results suggest that both subtypes of glutamate receptors are regulated in an activity-dependent way and that sensory stimulation transiently modifies local cortical processing.

Afferent Pathways↗

The involvement of dopamine in the striatum in passive avoidance training in the chick.

Quantitative receptor autoradiography was used to investigate the distribution of binding of [3H]SCH 23390 to dopamine (D1) and [3H]spiroperone to D2 receptors in regions of the forebrain of the one-day-old domestic chick (Gallus domesticus). High levels of specific binding of the D1 and D2 ligands were found in the striatal regions (paleostriatum augmentatum and lobus parolfactorius) of the one-day-old chick, as reported previously in the pigeon, turtle and rat, whilst binding levels were considerably lower in the pallidum (paleostriatum primitivum), hippocampus and hyperstriatum ventrale. The proportions of D1 and D2 receptor binding in the chick were relatively similar in the striatum and pallidum, apart from the paleostriatum augmentatum, where D2 receptors outnumber those of D1 by a factor of two. Binding of the D1 and D2 ligands to forebrain regions was also investigated 30 min after one-trial passive avoidance training of one-day-old chicks in which the aversive stimulus was a bead coated with a bitter tasting substance, methyl anthranilate. These experiments demonstrated a large and highly significant bilateral increase (compared to control birds) in binding to D1 (but not D2) receptors in the lobus parolfactorius. In this striatal region, equivalent to the caudate-putamen of mammals, previous studies have shown that synaptic and dendritic alterations occur following avoidance training. It is concluded that alterations in dopamine binding may be involved in processes that result in modification of the pecking response in chicks after avoidance training.

Animals↗

Overlap of sensory representations in rat barrel cortex after neonatal vibrissectomy.

Cortical representation of the common fur of mystacial pad is situated outside postero-medial barrel subfield (PMBSF) in rat primary somatosensory cortex. Following neonatal vibrissectomy, stimulation of the common fur activates the neurones in PMBSF. We examined if sparing of one mystacial vibrissa from the neonatal ablation, which results in a very extensive increase of its cortical representation, would prevent the invasion of the common fur inputs into the PMBSF. The cortical representations were mapped with 2-deoxyglucose (2DG). It was found that six weeks after neonatal vibrissectomy sparing C3 vibrissa and common fur inputs were represented in the PMBSF. Their representation shifted from its normal location into the barrel field. This effect was observed in cortical layers II/III, IV and V.

Animals↗

Partial blocking of NMDA receptors restricts plastic changes in adult mouse barrel cortex.

Changes of cortical body maps can be evoked in brains of adult animals by injury to sensory nerves. We investigated changes of functional representation of row C of mystacial vibrissae in the barrel cortex of mice. Plastic changes of cortical representations were mapped with 2-deoxyglucose autoradiography. Seven days after lesions of all vibrissae except row C, cortical representation of the spared row increased in width by 60%. Partial blocking of N-methyl-D-aspartate (NMDA) receptors by subdural implants of thin sheets of Elvax impregnated with DL-2-amino-5-phosphonovaleric acid (APV) prevented development of the increase of row C representation. Low level of NMDA receptor blocking did not affect significantly the basal level of 2DG uptake and stimulus evoked uptake but prevented the plastic change of the body map.

Animals↗