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Biomedical subjects

M Kossut

Publications and source records attributed to M Kossut.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

Elevated AP-1 transcription factor DNA binding activity at the onset of functional plasticity during development of rat sensory cortical areas.

The patterns of three transcription factor DNA binding activities, namely AP-1, Octamer and CREB, were examined in barrel and visual cortices of rat brain during early postnatal development, when activity-dependent plasticity of neuronal responses and connectivity was described. Main peak levels of AP-1 DNA binding activity have been observed at 21 days postnatally in both cortical areas. In addition, slightly elevated AP-1 levels were detected at 3-7 postnatal days in the barrel and in the visual cortex. In contrast, Octamer DNA binding activities were at the highest levels in both areas at 7 days postnatally, and CREB DNA binding activities were not appreciably modulated throughout the development. The AP-1 protein complex at 21 days postnatally was composed of JunD, JunB, Fra-2, FosB and to much lesser extent of c-Fos in both cortical areas. Treatment of 21 day old rats with MK-801, an NMDA receptor antagonist, provoked a dramatic decrease in AP-1 DNA binding activities in the barrel cortex, but not in the visual cortex. Elevated AP-1 DNA binding activity can be taken as a good correlate of an onset of functional plasticity in the rat sensory cortex, although in the two primary sensory cortices examined it seems to be regulated in different ways.

Aging↗
PubMed1995

NMDA receptors in mouse barrel cortex during normal development and following vibrissectomy.

The development of N-methyl-D-aspartate (NMDA) receptors and the effects of vibrissectomy upon [3H]MK-801 binding were examined in the barrel cortex of mice. Autoradiographic studies showed that initially very low binding of [3H]MK-801 sharply increased during the second postnatal week reaching the adult level by the end of the third week. Scatchard analysis performed on cortical membrane preparations indicated that this rise of [3H]MK-801 labelling was due to an increase in the number of binding sites and a decrease of Kd at postnatal day 15 and 28. The interlaminar differences of labelling were registered from postnatal day 8. Changes of interlaminar distribution were found during the second and third postnatal weeks. In adult barrel cortex the highest binding was found in supragranular layers. In layer IV of the cortex, the pattern of binding resembled the pattern of barrels. Unilateral denervation of vibrissae performed in neonatal and adult mice did not alter the intensity of [3H]MK-801 labelling or the laminar distribution of binding sites. These results suggest that NMDA receptor binding does not reflect the plastic changes occurring in the barrel cortex.

Analysis of Variance↗
PubMed1995

Temporal dynamics and regional distribution of [14C]serine uptake into mouse brain.

In order to examine the uptake of L-serine into brain structures and brain metabolic compartments, L-[U-14C]serine was injected into tail vein of mice. The uptake was examined 30 min, 90 min, 3 h and 5 h after injection by both quantitative autoradiography of coronal brain sections and by biochemical analysis. Brain radioactivity was extracted and partitioned into protein associated pellets, metabolites soluble in aqueous phase and lipids soluble in the organic phase. Most of the radioactivity was found in the aqueous phase, about 10% was incorporated into lipids. Among phospholipids the highest label was found in phosphatidylserine, then in phosphatidylethanolamine and in phosphatidylcholine, it amounted to 52%, 30% and 18% of label by 90 min after injection, respectively. The brain distribution of L-serine uptake resembled that described for strychnine-insensitive [3H]glycine binding, with cortical structures being preferentially labelled.

Animals↗
PubMed1994

Plasticity of mystacial fur representation in SI cortex of adult vibrissectomized rats--a 2DG study.

Localization of cortical representation of the common fur of mystacial pads was mapped with 2-deoxyglucose autoradiography in adult rats after vibrissectomy. Normal representation of mystacial fur was found in locations outside the posteromedial barrel subfield (PMBSF). Vibrissectomy performed in young adult resulted in fur inputs activating the PMBSF. This plastic change took more than two weeks and less than one month to complete.

Animals↗
PubMed1994

Reduction of GABAA receptor binding of [3H]muscimol in the barrel field of mice after peripheral denervation: transient and long-lasting effects.

The effect of peripheral sensory deprivation upon GABAA receptor binding of [3H]muscimol was investigated in the barrel cortex--cortical representation of mystacial vibrissae of mice--by means of in vitro quantitative autoradiography. Unilateral lesions of all vibrissae or selected rows of whiskers were performed neonatally or in adulthood. [3H]muscimol binding was examined after various survival times up to 60 days. Both types of lesions performed in adult mice resulted in a transient decrease (10-25%) of binding values in the deafferented areas of the barrel field as compared with the unoperated control side. Sixty days after denervation [3H]muscimol binding returned to control values. Similar results were found after neonatal removal of all vibrissae. Neonatal lesion of selected rows of vibrissae, however, resulted in a decrease of [3H]muscimol binding (by about 26%) lasting up to 60 days in corresponding rows of barrels. This last result was accompanied by severe cytoarchitectonic malformation of the barrel field. The results support the hypothesis that a decrease of inhibition plays a facilitatory role in the plastic reorganization of cortical circuitry.

Aging↗
PubMed1994

Short term changes of cortical body maps following partial vibrissectomy in adult mice.

Vibrissae-to-barrels pathway is often used as a model for investigating CNS plasticity. We examined early changes in the cortical representation of row C of vibrissae in adult mice, following vibrissectomy removing all whiskers except row C. The changes of cortical representation of the spared row of vibrissae were mapped with 2-deoxyglucose autoradiography. We found that one day after lesion of vibrissal follicles the areal extent of cortical representation of row C is smaller than normally, but 7 days post lesion it increases significantly, by 60 to 90%, in all cortical layers. Additionally, seven days post-lesion the intensity of labelling was increased in cortical layer V. The result suggest that plasticity that can be observed with 2-deoxyglucose mapping in the barrel cortex is not due to unmasking of existing connection, but to reorganization of connectivity at many levels.

Animals↗
PubMed1993

Loss of glutamate immunoreactivity from mouse first somatosensory (SI) cortex following neonatal vibrissal lesion.

Whisker follicles were surgically ablated (lesioned) on two entire rows (B and C) of the left snout of two groups of Swiss mice, in the first 2 days after birth (neonatally lesioned) with the animals being allowed to survive for 4 weeks. In the second group at 8 weeks of age (adults), the whisker follicles of rows B and C were similarly lesioned and a survival period of 3 days allowed. Glutamate-immunoreactivity (Glu-IR) was examined in tangential sections of the first somatosensory (SI) 'barrel' cortex of these two groups (at which time it was also confirmed that the follicles had not regrown). In the neonatally lesioned mice, barrel rows B and C were more poorly defined in the right (experimental) hemisphere sections and a semi-quantitative study showed that there was a decrease in Glu-IR cell number (up to 41%) in rows B and C of the right hemisphere compared to the spared barrel rows (A and D). The loss appears to occur over almost the entire area of each deprived barrel rather than being confined to the sides or hollows. In contrast to neonatally lesioned animals, the barrels of the adult-lesioned mice appeared intact and visually similar in both the experimental (right) and control hemispheres (left). The only notable change in Glu-IR observed in the adult-lesioned animals was a decrease of 38% in the number of Glu-IR cells in the sides between the two deafferented rows of barrels (B and C), compared to the cell number between the unaffected barrels (D and E), a change also seen in the neonatally lesioned mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Development of NMDA receptor-channel complex and L-type calcium channels in mouse hippocampus.

In vitro binding autoradiography was used to examine the pattern and intensity of binding of [3H]glutamate to NMDA receptors, [3H]MK 801 to NMDA receptor associated channels, and [3H]PN-200 110 to L-type calcium channels in the hippocampus of mice aged 3-70 days. The distribution of NMDA receptors and NMDA receptor associated channels was similar but not identical at the tested ages. Beginning with postnatal day 8, high binding levels were confined mostly to the hippocampal strata: the oriens and radiatum (CA1 and CA3 with [3H]MK 801 labeling but only CA1 with NMDA displaced [3H]glutamate labeling), the moleculare (higher labeling with [3H]MK 801 than with NMDA displaced [3H]glutamate binding), and the lucidum. The binding values for NMDA receptor-channel complex rose in the examined period (especially within the second and third week), reaching a plateau at the end of the third postnatal week. Sharp growth of binding within the second and third week of life was about 50% greater with [3H]MK 801 than with NMDA displaced [3H] glutamate labeling. L-type calcium channels were found to be most abundant in the strata: the oriens of the CA3 field, the moleculare, and the lucidum. The time course of binding value changes for the calcium channel was similar to the time course found for the NMDA receptor-channel complex.

Age Factors↗
PubMed1993

Effects of implantation of Alzet 1007D osmotic minipumps upon 2-deoxyglucose uptake in the cerebral cortex of mice.

The smallest Alzet osmotic minipumps (1007D) were implanted into mouse cerebral cortex. The flow of saline from a minipump produced a large necrosis of cortical tissue and still larger zone of decreased metabolic activity around the site of cannula implantation. Stimulus evoked uptake of 2-deoxyglucose located several millimeters from the implantation site was not affected.

Animals↗
PubMed1993

Metabolic conversion of phosphatidylserine via phosphatidylethanolamine into phosphatidylcholine in rat brain.

Exogenous, liposomal [14C]phosphatidylserine, and that synthesized from [14C]serine, were very slowly metabolized in cortex and hippocampus slices of rat brain; phosphatidylethanolamine (PE) formed from phosphatidylserine (PS) was not methylated to phosphatidylcholine (PC) for up to 6 hours of incubation. Among homogenates prepared from 7 separate brain regions, the cerebellum showed the highest, and the striatum and pons the lowest rate of PS synthesis and its further decarboxylation to PE; in all of these regions the stepwise methylation of PE to PC was very low. Isolated microsomal and mitochondrial fractions of whole rat brain, mixed together and incubated with [14C]serine and S-adenosylmethionine, displayed a high level of newly synthesized mitochondrial PE, and a low level of methylated PC in the microsomes. Moreover, PE formed in brain microsomes by the base exchange reaction was converted into PC in an insignificant range. These data show a limited activity for sequential methylation of PE into PC in rat brain, and suggest that it is probably not caused by the slow movement of mitochondrial PE.

Animals↗
PubMed1993

Functional plasticity and neurotransmitter receptor binding in the vibrissal barrel cortex.

A form of activity dependent, functional plasticity can be induced in the barrel cortex by sensory deprivation without damage to the sensory receptors. Changes of cortical representation of a spared C3 vibrissa, when all other whiskers were plucked out, were mapped with 2-deoxyglucose autoradiography in mice and rats after a short-lasting deprivation. An increase in the volume of cortical column activated by the spared vibrissa was found already after one week of deprivation. We have found previously that if deprivation is commenced immediately after birth, the changes in cortical representation of the spared whisker appeared in the third week of life. In search of a possible reason for the delayed expression of functional plasticity in neonatal animals we examined the developmental curves of neurotransmitter receptor binding for several transmitters though to be involved in plastic processes of the cerebral cortex. We found that the beta noradrenergic and muscarinic cholinergic receptor binding increased rapidly at the end of the second postnatal week and subsequently remained high. By contrast, the metabotropic glutamate receptor binding decreased during the first month of postnatal development. The AMPA receptors binding values rose during the first two weeks of life, and then decreased. Together with our previous data on the development of NMDA and GABAa receptor and voltage dependent calcium channel binding, the results suggest that slow development of functional plasticity in neonatal animals may be due to low levels of receptors of several neurotransmitters implicated in brain plasticity.

Animals↗
PubMed1992

Voltage-dependent L-type calcium channels in the development and plasticity of mouse barrel cortex.

Entry of calcium ions into the neuron is a triggering signal for initiation of several processes which may lead to modification of synaptic connectivity. The developmental changes of voltage-dependent L-type calcium channel (VDLCC) were studied using [3H]PN 200 110 nifedipine displaceable binding in the barrel cortex of mice, a model structure for studying cortical plasticity. In vitro binding autoradiography was used to examine quantitatively the pattern of [3H]PN 200 110 binding to brains of animals aged from 3 to 70 days. The binding values in the somatosensory cortex rose two-fold in the period examined, reaching a plateau in the 4th postnatal week. The laminar pattern of binding changed during development, with the locus of heaviest labeling shifting from layer IV to II/III in the third postnatal week and thin bands of labeling developing in layers IV and VI. A very faint barrel-like pattern of labeling in the barrel field was observed. Neither this pattern nor the binding values were altered by unilateral neonatal removal of all vibrissal follicles. Saturation studies of binding to crude synaptosomal fractions of cerebral cortex of mice aged 3, 15, 28 and 70 days revealed the presence of a single binding site, with Bmax increasing from 48.7 +/- 5.1 fmol/mg protein at postnatal day 3 to 191.7 +/- 9.6 fmol/mg protein at day 70. No developmental changes in KD values were found. No correlation was found between the critical period for cytoarchitectonic plasticity of the barrels and the time when high values of VDLCC binding were observed.

Aging↗
PubMed1992

Effects of sensory deprivation upon a single cortical vibrissal column: a 2DG study.

Effects of sensory deprivation upon ability of a vibrissa to activate a functional column in the barrel field of somatosensory cortex were examined with 2 deoxyglucose (2DG) autoradiography in the rat. After six weeks of whisker plucking started at birth, and one week of recovery, the cortical column activated by the deprived whisker and labeled with 2DG had a reduced diameter but higher labeling density than the normal vibrissal column. Loss of a peri-barrel labeling zone, possibly due to loss of intracortical activation, is suggested.

Animals↗
PubMed1992

5-HT1 receptors in the structures of visual pathway of normal and monocularly deprived kittens.

The density and pattern of distribution of 5-HT1 receptor sites was examined using quantitative in vitro autoradiography with [3H]5-HT as a ligand in the visual structures of 5 weeks old kittens. One group of animals had normal binocular vision, the other was monocularly deprived during the last three days of life. The density of 5-HT1 receptor sites and the pattern of their distribution in the visual structures showed distinct regional, areal and laminar differences. In the primary visual cortex (area 17) a high labelling density was found as compared with other cortical areas investigated. Three bands of high binding density were observed corresponding to cortical layers II-III, IV c and VI. This pattern distinguished area 17 from other cortical areas investigated. In subcortical visual structures very high labelling was present in the superficial visual layers of superior colliculus, but LGN showed rather weak labelling although the lamination of LGN was also seen in the pattern of distribution of 5-HT1 sites. Neither density nor pattern of 5-HT1 sites in the visual cortex and superior colliculus were affected by 3 days of monocular deprivation. High density of labelling and the distinct pattern of 5-HT1 receptor sites in the primary visual cortex suggest the important role of serotonergic transmission in the modulation of visual afferent input activity.

Animals↗