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Biomedical subjects

M F Bear

Publications and source records attributed to M F Bear.

At least 73 records · Page 4Linked to original sources
PubMed1990

Binocular competition in the control of geniculate cell size depends upon visual cortical N-methyl-D-aspartate receptor activation.

The lateral geniculate nucleus relays visual information from the retina to cortex. One well-known anatomical consequence of monocular deprivation during early postnatal development is a shrinkage of neurons in the lamina of the lateral geniculate nucleus that receive input from the deprived eye. This is thought to reflect the competition of afferents subserving the two eyes, possibly at the level of the visual cortex. We find that blockade of N-methyl-D-aspartate receptors in kitten visual cortex disrupts this process of binocular competition. These data provide direct evidence that postsynaptic activation of cortical neurons is required for competitive changes in lateral geniculate cell size and suggest a role for N-methyl-D-aspartate receptors in anatomical as well as physiological plasticity in the mammalian visual system.

2-Amino-5-phosphonovalerate↗
PubMed1990

Basal forebrain projections to somatosensory cortex in the cat.

1. This investigation was designed to identify the source of cholinergic basal forebrain projections to somatosensory cortex in the cat. 2. Injections of horseradish peroxidase (HRP) into cortical areas 3a, 3b, and 1 after a 36 to 48-h survival period, labeled neurons in the basal forebrain. The distribution of retrogradely labeled neurons was compared with the distribution of cells labeled by choline acetyltransferase immunocytochemistry. Most retrogradely labeled neurons in the basal telencephalon were found on the border between the globus pallidus and adjacent structures. Sometimes labeled neurons were also found in both limbs of the diagonal band of Broca. 3. Excitotoxin lesions of these regions of the basal telencephalon led to a profound depletion of acetylcholinesterase-containing axons in primary somatosensory cortex. 4. These data lay necessary groundwork for tests of the hypothesis that the cholinergic projection modulates experience-dependent modifications in adult cat somatosensory cortex.

Acetylcholine↗
PubMed1990

Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist.

To assess the possibility that NMDA receptors play a special role in visual cortical plasticity, the selective antagonist 2-amino-5-phosphonovaleric acid (APV) was continuously infused into the striate cortex of kittens as the visual environment was manipulated during the critical period. The cortex was studied using single-unit recording from sites between 3 and 6 mm from the infusion cannulae. One week of D,L-APV infusion coincident with monocular deprivation or "reverse suture" produced a concentration-dependent increase in the percentage of neurons that (1) lacked normal orientation selectivity and (2) were responsive to stimulation of the deprived eye. These effects outlasted the presence of the drug in the tissue. APV treatment also prevented the acquisition of selectivity and visual responsiveness that normally results from monocular visual experience after dark-rearing. Lasting effects of chronic APV infusion were not observed in adult striate cortex. The effects of APV on kitten striate cortex depended on the presence of the D stereoisomer as infusion of L-APV was without effect. Estimates of extracellular concentration using 3H-APV indicated that significant effects could be obtained with concentrations as low as 20 microM D,L-APV. Recordings from units during infusion indicated that visual responses were reduced by APV. Nonetheless, a normal percentage of visually responsive neurons was found at sites greater than or equal to 3 mm from the infusion cannula. There was no evidence that chronic APV infusion affected the sampling frequency of recorded neurons or disrupted cytoarchitecture at the sites further than 3 mm from the infusion cannula. Taken together, the data indicate that the effects of APV on kitten striate cortex are likely due specifically to the blockade of NMDA receptors. These data are considered in relation to several hypotheses concerning the role of NMDA receptors in the experience-dependent development of striate cortex.

2-Amino-5-phosphonovalerate↗
PubMed1989

A biochemical correlate of the critical period for synaptic modification in the visual cortex.

Stimulation of phosphoinositide hydrolysis by excitatory amino acids was studied in synaptoneurosomes of kitten striate cortex at several postnatal ages. Ibotenate and glutamate stimulated phosphoinositide turnover during the second and third postnatal months; N-methyl-D-aspartate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) were without effect. The developmental profile of ibotenate-stimulated phosphoinositide turnover parallels the postnatal changes in cortical susceptibility to visual deprivation. The transient increase in ibotenate-stimulated phosphoinositide turnover does not occur in visual cortex of kittens reared in complete darkness.

Aging↗
PubMed1989

Blockade of NMDA-receptors prevents ocularity changes in kitten visual cortex after reversed monocular deprivation.

We investigated in the striate cortex of kittens whether the recovery from the effects of monocular deprivation that occurs after reverse occlusion requires activation of N-methyl-D-aspartate (NMDA) receptors. The right eye of 3-4-week-old kittens was closed by lid suture for one week. Subsequently this eye was reopened and the left eyelid sutured closed for another week. During this second week, the NMDA-receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), was infused from an osmotic minipump into the left visual cortex (50 nmol/h), while the right visual cortex was infused only with vehicle solution (saline) as control. At the end of the second week, the ocular dominance of striate cortical neurons was assessed with single unit recording. In the control hemispheres, the large majority of neurons was dominated by the newly opened eye, while in the APV-treated hemispheres most neurons were still dominated by the newly deprived eye. In addition, neurons in the APV-treated hemispheres were less responsive and showed a reduction of orientation tuning. These data confirm that chronic blockade of cortical NMDA-receptors disrupts the disconnection of deprived pathways after monocular deprivation and reduces both responsiveness and orientation selectivity of cortical neurons. In addition they indicate that blockade of NMDA-receptors prevents also vision-dependent recovery of deprived pathways after reverse occlusion.

2-Amino-5-phosphonovalerate↗
PubMed1989

Postnatal changes in glutamate stimulated phosphoinositide turnover in rat neocortical synaptoneurosomes.

Glutamate was found to stimulate the accumulation of [3H]inositol phosphate in synaptoneurosomes prepared from rat neocortex during a narrowly defined period of postnatal development. No glutamate stimulation was observed on the day of birth, even though high levels of phosphoinositide (PIns) turnover were observed with the muscarinic agonist carbachol. Glutamate-stimulated PIns turnover reached a maximum at one week of age, and decreased to adult levels by five weeks of age. Of the glutamate analogs tested, only ibotenate produced significant stimulation. N-Methyl-D-aspartate (NMDA) showed negligible stimulation and kainate showed only minor stimulation at the highest concentration tested (1 mM). Glutamate stimulation was not blocked by either the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) or the broad spectrum glutamate antagonist kynurenic acid. These results suggest that a specific subclass of excitatory amino acid receptor linked to PIns metabolism, or a phospholipase associated with the receptor, is transiently expressed in the neocortex during early postnatal development.

Aging↗
PubMed1989

Visual experience regulates gene expression in the developing striate cortex.

We have examined the regulation of expression of the genes for the neuronal growth-associated protein GAP43, the type II calcium/calmodulin-dependent protein kinase, and glutamic acid decarboxylase in the kitten visual cortex during normal postnatal development and after a period of visual deprivation. We find that the mRNA transcripts of these genes display very different patterns of normal development but are all increased in the visual cortex of animals reared in the dark. Upon exposure to light, the transcript of the GAP43 gene drops to near-normal levels within 12 hr.

Aging↗
PubMed1988

Experience-dependent modifications of kitten striate cortex are not prevented by thalamic lesions that include the intralaminar nuclei.

It has been shown previously that surgical lesions of the antero-medial thalamus interfere with ocular dominance modifications that normally result from monocular deprivation in young kittens (Singer 1982). The aim of the present study was to determine whether this effect was due specifically to the destruction of the visual cortical projections of the anterior intralaminar nuclei. We report here that large excitotoxin lesions of the anterior dorsal thalamus have no effect on the cortical response to monocular deprivation. These data indicate that the intralaminar projection is not essential for ocular dominance plasticity.

Animals↗
PubMed1987

Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex.

Intracortical infusion of the "N-methyl-D-aspartate" (NMDA) receptor blocker D,L-2-amino-5-phosphonovaleric acid (APV) renders kitten striate cortex resistant to the effects of monocular deprivation. In addition, 1 week of continuous APV treatment (50 nanomoles per hour) produces a striking loss of orientation selectivity in area 17. These data support the hypothesis that crucial variables for the expression of activity-dependent synaptic modifications are a critical level of postsynaptic activation and calcium entry through ion channels linked to NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1987

A physiological basis for a theory of synapse modification.

The functional organization of the cerebral cortex is modified dramatically by sensory experience during early postnatal life. The basis for these modifications is a type of synaptic plasticity that may also contribute to some forms of adult learning. The question of how synapses modify according to experience has been approached by determining theoretically what is required of a modification mechanism to account for the available experimental data in the developing visual cortex. The resulting theory states precisely how certain variables might influence synaptic modifications. This insight has led to the development of a biologically plausible molecular model for synapse modification in the cerebral cortex.

Action Potentials↗
PubMed1985

Postnatal changes in the distribution of acetylcholinesterase in kitten striate cortex.

We have traced the postnatal development of axons and cells in kitten striate cortex that contain acetylcholinesterase (AChE) by using a modification of Koelle's histochemical method. The maturation of AChE-positive axons was not found to be fully complete until at least 3 months of age, and was characterized by several distinct developmental trends. AChE-positive fibers in layers IVc-VI proliferate rapidly after birth until, by 4 weeks postnatal, they appear to exceed the adult density. They remain at this level as late as 8 weeks and then decrease to the adult density by 13 weeks. In contrast, the AChE-positive fibers in layer I do not show a substantial increase in density until 6 weeks of age and the adult level is not achieved before 3 months postnatal. Finally, the density of AChE-positive fibers in layers II and III appears to increase gradually from birth until the mature pattern is reached at about 6 weeks. AChE could also be localized histochemically to cell bodies whose position and appearance depended on postnatal age. Stained cells first appeared in the white matter subjacent to layer VI shortly after birth. By 2 weeks of age, most cells in layer VI were also AChE positive. The staining of these cells gradually disappears over the next 2 months until, at 3 months of age, there are no AChE-positive cells in cat striate cortex. However, a subpopulation of stained neurons appears in layer V by 1 year of age that persists throughout adulthood. The possible contributions of acetylcholine and AChE to the postnatal development of kitten striate cortex are discussed.

Acetylcholinesterase↗
PubMed1985

Glutamic acid decarboxylase activity decreases in mouse neocortex after lesions of the basal forebrain.

Glutamic acid decarboxylase (GAD) activity was measured in the cerebral cortex of animals after acute and chronic lesions to basal forebrain cholinergic nuclei. Such lesions were shown to result in an extensive depletion of cholinergic markers in parietal cerebral cortex. A statistically significant 30% decrease in GAD activity was first detected at 6 weeks postlesion and was still measurable 8 months after the lesion. These results suggest that cholinergic inputs to cortex indirectly or directly influence GABAergic transmission in cortex.

Animals↗
PubMed1985

An investigation of cholinergic circuitry in cat striate cortex using acetylcholinesterase histochemistry.

The organization of cholinergic inputs to cat striate cortex (area 17) was studied by using a histochemical stain for acetylcholinesterase (AChE). Axons were labelled in all layers of the striate cortex, with distinct plexuses occurring in layer I, lower layer III, layer IVc, and layer VI. In addition to the stained axons, a population of layer V pyramidal cells was intensely AChE-positive. Surgical undercutting eliminated virtually all of the AChE-positive axons in the striate cortex, thus indicating that this innervation arises entirely from an extrinsic source in the cat. To identify this source, cell groups projecting to area 17 were retrogradely labelled with horseradish peroxidase. Cell groups labelled with horseradish peroxidase that were also intensely AChE-positive were considered as possible candidates for providing the cholinergic input to the striate cortex. These included the basal forebrain, several intralaminar nuclei, and the lateral geniculate nucleus. Kainate lesions were then made in each of these structures to assess their individual contributions to the cortical AChE pattern. Cortical AChE was depleted only after lesions of the basal forebrain, suggesting that this is the sole source of AChE-positive axons in area 17. Because the cortically projecting cells in this region have been shown to contain choline acetyltransferase in a number of species, we postulate that the AChE-positive fibers we describe in the cat striate cortex are in fact cholinergic.

Acetylcholinesterase↗
PubMed1985

Glutamic acid decarboxylase in the striate cortex of normal and monocularly deprived kittens.

Degeneration of the thalamic fibers in the visual cortex of turtles leads to an increase in the numerical density of cortical synapses with flattened vesicles and symmetrical membrane differentiations (Smith, L. M., and F. F. Ebner (1980) Soc. Neurosci. Abstr. 6: 328). This change correlates with an increase in the cortical activity of glutamic acid decarboxylase (GAD), the synthetic enzyme for gamma-aminobutyric acid (GABA). These data are consistent with the hypothesis that removal of thalamic input activity is the stimulus for cortical GABAergic neurons to form new synapses. Pharmacological evidence suggests that even simple environmental deprivation may induce a similar increase in the numerical density of GABAergic synapses in kitten striate cortex (Duffy, F. H., S. R., Snodgrass, J. L. Burchfiel, and J. L. Conway (1976) Nature 260: 256-257). We have examined this possibility in monocularly deprived kittens using methods to localize and measure GAD. GAD in kitten striate cortex was localized using immunocytochemistry. GAD-positive cells were found in all layers and were uniformly distributed in layers II to VI. Immunoreactivity associated with axon terminals (puncta), in contrast, was laminated with a distinct band in layer IV. Monocular deprivation (MD), by either unilateral enucleation or lid closure, had no detectable effect on the distribution of GAD in striate cortex. The band of layer IV puncta remained uniform even under conditions that produced alterations in layer IV cytochrome oxidase activity. We measured GAD activity in homogenates of striate cortex to address the possibility that MD causes an absolute change in the density of GABAergic synapses. Again, however, GAD activity in the binocular and monocular segments of striate cortex was found to be unaffected by early enucleation. These data suggest two conclusions: first, that the numerical density of GABAergic synapses in visual cortex is not regulated directly by thalamic activity, and second, that changes in GABAergic synapse density do not account for the ocular dominance shift observed in kitten striate cortex after MD.

Animals↗
PubMed1984

The stability of 6-hydroxydopamine under minipump conditions.

A number of investigators have recently used osmotic minipumps to continuously deliver the neurotoxin 6-hydroxydopamine (6-OHDA) to kitten cerebral cortex for periods up to 7 days. Because this compound is known to be particularly labile, we studied the stability of 6-OHDA stored under conditions similar to those found in an osmotic minipump. In 0.4% ascorbic acid, 4 mM 6-OHDA-HBr was found to be stable for at least one week as determined by (1) assay of the drug by high performance liquid chromatography and electrochemical detection and (2) test of the drug's ability to deplete mouse heart norepinephrine.

Animals↗
PubMed1983

Somatostatin-like immunoreactivity in the forebrain of Pseudemys turtles.

Previous investigations of cortical organization in the brain of the turtle have revealed many features typical of mammalian neocortex. Recent evidence suggests that many neocortical neurons contain neuroactive peptides. The possibility that one such peptide, somatostatin, is found in the turtle brain was tested using immunocytochemical techniques. Intense somatostatin-like immunoreactivity was observed in many neurons and fibers in turtle cortex, as well as in several forebrain nuclei. Cortical neurons with several different dendritic configurations showed immunoreactive labelling, including bipolar, stellate and pyramidal cell types. In addition, stained cells and processes were observed in close association with the ependyma of the lateral ventricle. Other forebrain regions containing immunoreactive neurons included the dorsal ventricular ridge, the basal telencephalic nuclei and the hypothalamus. These data support the idea that peptidergic neurons existed in the pallium of an ancestor common to modern mammals and reptiles. We speculate that somatostatin plays a similar role in the normal function of all types of cortex and suggest that turtle cortex may provide a useful model for the study of this cortical neuropeptide.

Animals↗
PubMed1983

The plastic response to monocular deprivation persists in kitten visual cortex after chronic depletion of norepinephrine.

In order to clarify the role of norepinephrine (NE) in visual cortical plasticity, we monocularly deprived kittens that had received systemic injections of the neurotoxin 6-hydroxydopamine (6-OHDA) shortly after birth. We found, using high pressure liquid chromatography, that this means of drug treatment produces a permanent and substantial reduction in the level of cortical NE as compared with littermate controls. Nonetheless, single unit recording in area 17 of these kittens revealed no difference in the cortical response to monocular deprivation: both drug-treated and control kittens displayed large ocular dominance shifts to the open eye. Because local depletion of NE by intracortical 6-OHDA in kittens can prevent the expected ocular dominance shift after short-term monocular deprivation, we propose that neocortex has the capacity to compensate for chronic depletion of NE in a way which allows for the possibility of plastic changes.

Animals↗