Biomedical subjects

G D Mower

Publications and source records attributed to G D Mower.

At least 19 recordsLinked to original sources

PubMed1997

Expression of two forms of glutamic acid decarboxylase (GAD67 and GAD65) during postnatal development of the cat visual cortex.

The postnatal development of GAD67 and GAD65 protein expression and of GAD67 positive neurons and GAD65 containing axon terminals in cat visual cortex was studied. Western blot analysis showed that the expression of both GAD67 and GAD65 increased to approximately two-thirds of the adult level during the first 5 postnatal weeks and gradually increased thereafter. In adult cats, immunohistochemistry showed that GABA and GAD67 containing neurons were found in all cortical layers. Faint cell body staining was seen with the antibody to GAD65, but it densely labeled puncta. In neonates, GABA and GAD67 immunoreactivity was most intense in two distinct bands, one superficial (Layer 1/Marginal zone), another deep (Layer VI/Subplate). Unlike in adults, GAD65 positive cell bodies were clearly evident in neonates and distributed similarly to, but less frequently than, GABA and GAD67. These GAD65 positive cells frequently had morphologies suggestive of embryonic cells and largely disappeared in older animals. During postnatal development, the neurochemical differentiation of GAD67 positive neurons and GAD65 positive axon terminals across visual cortical laminae followed an inside-outside developmental pattern, which reached adult levels after 10 weeks of age. These results suggest that postnatal development of the visual cortical GABA system involves three distinct processes: (A) a dying off of embryonic GABA cells which could play a role in formation of the cortical plate; (B) a period of relative quiescence of the VC GABA system in the first 5 postnatal weeks which could maximize excitatory NMDA effects during the rising phase of the critical period; (C) the prolonged postnatal maturation of the adult GABA system which could be involved in the crystallization of adult physiological properties and the disappearance of neural plasticity.

Aging↗

PubMed1996

Immediate early gene expression in cat visual cortex during and after the critical period: differences between EGR-1 and Fos proteins.

Immediate early gene (IEG) expression in the cat visual cortex is highly responsive to visual input and may initiate genetic mechanisms responsible for neuronal plasticity. The present study used immunohistochemical methods to address two issues regarding IEG expression in response to visual input. One was to define the differential response of distinct IEG families by comparing EGR-1 (also termed zif-268, NGFI-A, and Krox-24) and Fos proteins. The second was to determine whether IEG expression, in addition to reflecting neural activity, is related to the state of plasticity by comparing young and adult visual cortex. Immunoreactivity of the two IEG proteins was compared between 5-week-old and adult cats under three conditions of visual input: ambient light to assess basal levels of expression, 1 week of darkness to assess the effect of reduced activity, and exposure to light after 1 week of darkness to determine rapid changes in expression as a result of visual input. At both ages, there were marked differences in the expression of the two IEG proteins. EGR-1 responded to visual input with sustained changes in its level of expression. It showed high basal levels, reduced expression in darkness, and a rapid return to high constitutive levels with the introduction of light. Fos showed a markedly different profile. It had very low basal expression which was not demonstrably affected by darkness and its principal response was a marked transient induction upon exposure to light after darkness. These unique changes in expression highlight the complex response across IEGs to environmental input and suggest a genetic "on/off' signaling mechanism. There were marked differences in the laminar distribution of EGR-1 and Fos proteins between young and adult cats. In young animals, cells in all visual cortical layers showed high levels of EGR-1 and Fos proteins. In adults, immunostaining was largely specific to cells located above and below layer IV and only very faint labeling occurred within layer IV. These differences in laminar distribution between ages are inconsistent with a simple explanation of IEG expression in terms of neural activity level; rather, they suggest a relation between IEG expression and the state of plasticity in visual cortex.

Animals↗

PubMed1995

Developmental expression of the immediate early gene EGR-1 mirrors the critical period in cat visual cortex.

Immediate early gene (IEG) expression in the central nervous system is thought to play a role in coupling extracellular stimulation with the transcriptional events responsible for long-term functional changes in neurons. The goal of the present study was to determine the postnatal developmental profile of EGR-1 protein (also termed zif268, Krox-24, NGFI-A) expression across the layers of cal visual cortex and relate it to the state of visual cortical development and plasticity. Using a polyclonal antibody, EGR-1 immunoreactivity was studied in animals of various postnatal ages (from 0.5 week to adult). In very young animals (0.5 weeks), EGR-1 positive cells were restricted to deep cortical layers (layer VI/Subplate). With the increasing age, EGR-1 immunoreactivity spread across layers of the visual cortex in an inside-outside manner, and by 5 weeks of age, EGR-1 protein was highly expressed in all layers. EGR-1 expression remained high until approximately 10 weeks of age and then gradually began to decline in layer IV with little change in supra- and infragranular layers. In adult animals, EGR-1 was located predominantly in the layers above and below layer IV. This pattern of EGR-1 expression in developing cat visual cortex has both temporal and laminar similarities with the development of visual cortical connectivity, with the development of orientation selective receptive field properties, and with the level of visual cortical plasticity, suggesting an involvement of EGR-1 expression in these processes.

Animals↗

PubMed1994

Differences in the induction of Fos protein in cat visual cortex during and after the critical period.

The aim of this study was to compare the inducibility of Fos protein, in terms of magnitude and laminar distribution in visual cortex, between young (5-week-old) and adult cats. Immunohistochemical methods were used to detect Fos protein in visual and frontal cortex of young and adult cats who experienced brief (1 or 4 h) visual experience after a 1 week period of total darkness. In the 5-week-old kittens, densely stained Fos-immunoreactive neurons were found throughout all visual cortical layers as a result of 1 h of visual experience. In the adults, immunoreactive cells were concentrated in supra- and infragranular layers and only very faint labeling was found in layer IV. Immunoreactivity in young kittens persisted at much greater dilutions of primary antibody than in adults, suggesting a difference in the magnitude of induction between ages. The inductions were markedly greater in visual than in frontal cortex, where only scattered immunopositive cells were seen at the highest antibody concentration. The induction of Fos protein in visual cortex was transient and largely disappeared by 4 h at both ages. The differences between ages, both in the magnitude and laminar distribution of immunoreactivity, are inconsistent with a simple explanation of Fos inductions in terms of neural activity level. Rather, these results suggest a relation between Fos inducibility and the level of plasticity in visual cortex.

Aging↗

PubMed1994

Localization of cystatin mRNA in chicken brain by in situ hybridization.

The cystatins are a superfamily of proteins that inhibit the lysosomal cysteine proteinases, cathepsins B, H, and L. Members of this superfamily have been found in all tissues and biological fluids analyzed. Previous studies have shown that chicken cystatin mRNA is abundant in brain tissue. In this study, a definitive localization of chicken cystatin mRNA in chicken brain was determined by in situ hybridization. Chicken cystatin mRNA was heavily concentrated in the secretory epithelial cells of the choroid plexus. The rest of the brain failed to show a hybridization signal above that of the control sense strand probe, even after long exposures. We conclude that chicken cystatin is synthesized predominantly by the specialized secretory epithelial cells of the choroid plexus and secreted into the cerebrospinal fluid (CSF). We postulate that chicken cystatin functions to regulate proteinase activity in the CSF and therefore may function as a protective factor for the cellular elements of the central nervous system.

Animals↗

PubMed1993

Differences in c-fos immunoreactivity due to age and mode of seizure induction.

The aim of this study was to determine whether the regional distribution and time course of immunoreactivity to the c-fos protein varies with maturation and method of seizure induction. The effect of the two chemical convulsants, pentylenetetrazol (PTZ) and flurothyl, on the spatial and temporal pattern of c-fos-like immunoreactivity in immature (postnatal day (P) 10) was compared to that in adult rats. Patterns of c-fos-like immunoreactivity following O2 deprivation were also evaluated at the 2 ages because hypoxia is acutely epileptogenic in immature animals but not adults. C-fos-like immunoreactivity was examined at 2, 4, and 6 h after onset of chemically induced seizures or O2 deprivation at both ages. After PTZ or flurothyl seizures, both ages exhibited similar patterns of IR in amygdala, pyriform cortex, and hypothalamus. Age-dependent regional differences were most prominent in cortex: superficial layers of retrosplenial, cingulate, and neocortex stained in adults; staining was confined to deep layers of neocortex in P10 rats. Intense staining of dentate gyrus and hippocampus occurred with more prolonged seizures, but not brief seizures. PTZ administration resulted in staining at 2 h after seizure onset and was reduced by 4 h in adults, but immunoreactivity was not seen until 4 and 6 h after seizure onset in immature rats, indicating an age effect on the time course of IR. In immature rats, immunoreactivity patterns after hypoxia were markedly different from PTZ or flurothyl: staining was confined to layer VI of neocortex in these animals, and rarely involved limbic structures. These differences in the pattern of c-fos immunoreactivity suggest that the neuronal populations involved in epileptogenesis are influenced by age as well as seizure phenotype and intensity.

Aging↗

PubMed1993

Developmental and environmental changes in GAP-43 gene expression in cat visual cortex.

Northern/slot blot analysis was used to determine postnatal developmental and environmentally induced changes in the level of expression of GAP-43 mRNA in visual and frontal cortex. Both structures showed a precipitous decline during the first 5 weeks and a slight further decline to adult levels. Dark rearing resulted in a significant elevation of GAP-43 mRNA which was eliminated by brief visual experience. This effect was specific to visual cortex and did not occur in frontal cortex. The effect also did not occur in normal adult cats placed in prolonged darkness, indicating that GAP-43 mRNA levels are not simply activity dependent and are altered by visual input only during early postnatal life. These results are consistent with a role for GAP-43 in the state of visual cortical plasticity.

Animals↗

PubMed1992

Brief visual experience induces immediate early gene expression in the cat visual cortex.

Brief visual experience causes rapid physiological changes in the visual cortex during early postnatal development. A possible mediator of these effects is the immediate early genes whose protein products are involved in the rapid response of neurons to transsynaptic stimulation. Here we report evidence that the levels of immediate early gene mRNAs in the visual cortex can be altered by manipulating the visual environment. Specifically, we find that brief (1 h) visual experience in dark-reared cats causes dramatic transient inductions of egr1, c-fos, and junB mRNAs in the visual cortex but not in the frontal cortex. Levels of c-jun and c-myc mRNAs are unaffected. These results suggest that select combinatorial interactions of immediate early gene proteins are an important step in the cascade of events through which visually elicited activity controls visual cortical development.

Animals↗

PubMed1992

Changes in immediate early gene expression during postnatal development of cat cortex and cerebellum.

Postnatal brain development involves interactions between extracellular signals and preprogrammed genetic events. Immediate early genes (IEGs) are a group of genes that are induced by extracellular signals and their protein products alter transcription by binding regulatory elements in other genes. Using Northern and slot blot analysis of total RNA isolated from visual cortex, frontal cortex, and cerebellum of cats, we have determined the postnatal development patterns of mRNA expression for 5 of these genes, c-fos, erg-1, c-jun, jun-B, and c-myc. Each gene had a distinct developmental pattern of mRNA expression, and for a given gene, these patterns were often different in different brain structures. These results suggest that temporal changes in the combinatorial interaction of different IEGs during early postnatal life are important for normal brain development.

Aging↗

PubMed1991

Comparison of serotonin 5-HT1 receptors and innervation in the visual cortex of normal and dark-reared cats.

The visual cortical serotoninergic system was compared in normal and dark-reared cats to determine whether visual experience is necessary for its normal development. In vitro receptor binding of [3H]5-HT indicated an increase in 5-HT1 receptor number in dark-reared cats with no change in affinity. This elevation was specific to the visual cortex and no changes were found in the frontal cortex as a result of dark rearing. Autoradiographic histology revealed that in the normal cat visual cortex, 5-HT1 receptors were present in all cortical layers and were slightly more dense in supragranular and infragranular layers. In dark-reared cats, there was a marked elevation in receptor density in supragranular and infragranular layers and little change within layer IV. Immunohistochemical techniques (anti-5-HT) were used to compare serotoninergic innervation in the visual cortex of normal and dark-reared cats. In normal cat visual cortex, serotonin fibers were most dense in the superficial layers (I-III), least dense in layers IV and VI, and intermediate in layer V. No differences were found between normal and dark-reared cats in the laminar distribution or density of serotoninergic innervation. These results indicate that visual experience is necessary for the normal development of the visual cortical serotonin system. The findings that the effects of dark rearing were specific to the visual cortex and that within the visual cortex these effects were specific to supra- and infragranular layers are consistent with a possible role for serotonin in the prolonged physiological plasticity that occurs in the visual cortex of dark-reared cats.

Animals↗

PubMed1991

The effect of dark rearing on the time course of the critical period in cat visual cortex.

The effects of dark rearing on the time course of the postnatal critical period for monocular deprivation (MD) in visual cortex were determined in cats who experienced 2 days of MD at various postnatal ages. In normal development, plasticity (susceptibility to MD) was very low at 3 weeks, rose sharply at 6 weeks, and gradually declined over the next 10 weeks. This developmental profile was dramatically altered by dark rearing which slowed the entire time course of the critical period. In dark reared cats, plasticity rose steadily over the first 12 weeks, and was maintained at 16 weeks. There was a crossover of the two profiles of the critical period such that at young ages (6 weeks) normal cats were more plastic than dark reared cats while at later ages (after 9 weeks) dark reared cats were more plastic. A second experiment indicated that dark rearing slowed down the progression of the critical period even after it had been initiated by a period of normal vision. MD produced substantial effects after the normal critical period in cats who were reared normally for the first 6-8 weeks of life and then placed in darkness until 5 months of age. The results are discussed in terms of a simple model of the accelerating effect of visual input and the decelerating effect of total darkness on the time course of the critical period.

Animals↗

PubMed1989

Evidence for an enhanced role of GABA inhibition in visual cortical ocular dominance of cats reared with abnormal monocular experience.

The effects of microiontophoretic bicuculline, a gamma-aminobutyric acid (GABA) antagonist, on the ocular dominance of visual cortical neurons were compared in normal cats and cats reared with abnormal monocular visual experience (monocular deprivation, surgical strabismus, and monocular deprivation after dark rearing). Cells that were monocular prior to drug application showed disinhibitory effects on ocular dominance far more frequently than originally binocular cells in all rearing conditions. When the total population of neurons was considered there were marked differences among rearing conditions: only 17% of cells showed change in ocular dominance in normal cats whereas over 50% showed changes in cats reared with abnormal monocular visual experience. These results indicate that GABA inhibition plays an enhanced role in cats with abnormal cortical ocular dominance. The results are interpreted in the context that the GABA system is passively biased by alterations in the pattern of excitatory input to contribute to abnormal patterns of ocular dominance.

Animals↗

PubMed1988

Quantitative comparisons of gamma-aminobutyric acid neurons and receptors in the visual cortex of normal and dark-reared cats.

Physiological studies suggest that the function of the visual cortical gamma-aminobutyric acid (GABA) system is abnormal in cats reared in total darkness. The present study asked whether visual input is necessary for the normal postnatal anatomical development of the GABA system by comparing GABA neurons and receptors in the visual cortex of normal and dark-reared cats. Immunohistochemical techniques (anti-GABA) were used to localize GABA neurons. In both rearing conditions, GABA neurons were stained rather uniformly in all cortical layers. Counts of GABA cells indicated a marked increase in density in dark-reared compared to normal cats. Counts of total cellular density in cresyl-stained sections, however, indicated a comparable increase in dark-reared cats. When corrected for total cellular density, there were no differences between dark-reared and normal cats in the density of GABA cells per layer, or the relative proportion of GABA cells across cortical layers. In vitro receptor binding of 3H-muscimol was used to compare GABAA receptors in the two rearing conditions. When corrected for total cellular density, saturation kinetics indicated no difference in the total number or affinity of receptors. Similarly, autoradiographic histology indicated no difference in the laminar distribution of receptors across cortical layers between dark-reared and normal cats. These results indicate that the postnatal development of GABA neurons and receptors occurs normally in the absence of visual input.

Aging↗

PubMed1987

Effects of monocular occlusion and diffusion on visual system development in the cat.

The effects of two forms of monocular deprivation (occlusion or diffusion) on visual system development were investigated. One group of cats monocularly deprived of all form stimulation but permitted diffuse light stimulation (diffusion, n = 4) during development showed a pattern of deficits similar to those reported for monocularly sutured cats. Most cells in the visual cortex were driven exclusively by the non-deprived eye and there were eye-specific deficits in X-cell acuity, proportion of Y-cells, and cell body size (binocular and monocular segment) in the lateral geniculate nucleus (LGN). A second group of cats monocularly deprived of all form and light stimulation (occlusion, n = 4) during development showed a less severe pattern of deficits. There was no acuity loss in LGN X-cells driven by the deprived eye, and cell body shrinkage was of smaller magnitude than in diffusion reared cats and was restricted to the binocular segment. Cortical deficits and LGN Y-cell loss were similar in the two groups. The results are consistent with the idea that monocular occlusion produces only deficits due to binocular competition while monocular diffusion reflects the combined effects of binocular competition and abnormal stimulation.

Animals↗

PubMed1986

[3H]muscimol binding of GABA receptors in the visual cortex of normal and monocularly deprived cats.

In vitro receptor binding techniques were used to compare the total number, affinity and regional distribution of GABA receptors in visual cortex, as revealed by [3H]muscimol binding, in 5 normal and 5 monocularly deprived (MD) cats. Analysis of saturation kinetics and pharmacological specificity indicated that binding was to a single site having the characteristics of the GABAA receptor. No differences were found between normal and MD cats in either number or affinity of receptors. Within visual cortex, there were laminar differences in the density of binding, but no evidence for a lateral (columnar) organization. Label was densest in the superficial layers (I-IV), lowest in layer V and intermediate in layer VI. This pattern of label varied with incubation parameters with layer IV showing the densest label when high concentrations of [3H]muscimol and short rinse times were used. There were no differences between normal and MD cats in regional distribution of receptors under any incubation condition.

Animals↗

PubMed1985

Comparative pharmacological effects on visual cortical neurons in monocularly deprived cats.

Monocularly deprived (MD) cats show a loss of responsiveness to visual stimulation of the deprived eye among visual cortical neurons. Several lines of evidence suggest that this effect involves, at least in part, a suppression of deprived eye input, possibly mediated by GABA inhibition. In order to better understand the nature of this suppression we have evaluated the effectiveness of different types of disinhibitory and excitatory agents to reverse the effects of MD. We investigated bicuculline (a GABA antagonist); picrotoxin (a GABA antagonist with a different mechanism of action from bicuculline); strychnine (a glycine antagonist); ammonium ion (a blocker of membrane chloride channels); physostigmine (a cholinesterase inhibitor); and naloxone (an opiate antagonist and also a GABA antagonist). All drugs were given intravenously. Bicuculline restored binocularity to 50% of the visual cortical neurons tested and naloxone to 36%. With both drugs, receptive fields of the normal eye tended to lose specificity. The emergent deprived eye receptive fields were usually similar to those of the normal eye after drug administration. Ammonium ion produced binocular responses in 27% of neurons tested, but receptive fields were grossly abnormal; moreover, ammonium infusion tended to depress neuronal responsiveness. All other drugs tested failed to restore binocularity. These experiments lend further credence to the hypothesis that GABA inhibition contributes to the cortical effects of MD, since only drugs with GABA antagonistic action were effective in restoring neuronal responsiveness to the deprived eye.

Acetates↗

PubMed1985

Dark rearing prolongs physiological but not anatomical plasticity of the cat visual cortex.

Recent studies (Cynader and Mitchell, '80; Mower et al., '81) have shown that total dark rearing prolongs susceptibility to the physiological effects of monocular deprivation (MD) in visual cortex beyond the normal age limits. The present study addressed whether this delayed physiological plasticity is accompanied by delayed anatomical plasticity in the geniculocortical pathway. Ocular dominance (OD) columns as defined by transsynaptic autoradiography following injection of 3H proline into one eye were studied both qualitatively and quantitatively in 17 cats. Compared to normal rearing (N-3), both binocular eyelid suture (N-2) and total dark rearing (N-3) resulted in incomplete segregation of OD columns in area 17. This apparent immaturity after binocular deprivation, however, did not reflect a delayed capacity for development and plasticity. Visual experience after dark rearing produced no marked changes. In cats who experienced MD after dark rearing, injection of either the nondeprived (N-2) or deprived eye (N-3) resulted in a nearly uniform distribution of label throughout layer IV of area 17. The same result occurred with binocular vision after dark rearing (N-1). MD from birth, however, produced expansion of columns from the nondeprived eye (N-1) and contraction of columns from the deprived eye (N-1). MD imposed after 4 months of normal vision resulted in normal OD columns (N-1). Electrophysiological studies revealed a high proportion of binocular cells within layer IV in cats who experienced monocular or binocular vision after dark rearing. Outside of layer IV there were clear environmental effects on OD of single cells in these cats. Measurements of cell sizes in the clateral geniculate nucleus showed shrinkage of cells innervated by the deprived eye when MD was initiated at birth (N-3). MD after dark rearing (N-4) produced no differences in cell sizes. It is concluded that visual input is necessary for the formation of normal OD columns, the critical period for formation and environmental modification of OD columns is limited to early life, and the physiological effects of visual experience after dark rearing reflect changes occurring beyond the geniculocortical pathway.

Animals↗

PubMed1985

Role of visual experience in activating critical period in cat visual cortex.

Cats were reared in total darkness from birth until 4-5 mo of age (DR cats, n = 7) or with very brief visual experience (1 or 2 days) during an otherwise similar period of dark rearing [DR(1) cats, n = 3; DR(2) cats, n = 7]. Single-cell recordings were made in area 17 of visual cortex at the end of this rearing period and/or after a subsequent prolonged period of monocular deprivation. Control observations were made in normal cats (n = 3), cats reared with monocular deprivation from birth (n = 4), and cats monocularly deprived after being reared normally until 4 mo of age (n = 2). After rearing cats in total darkness, the majority of visual cortical cells were binocularly driven and the overall distribution of ocular dominance was not different from that of normal cats. Orientation-selective cells were very rare in dark-reared cats. Monocular deprivation imposed after dark rearing resulted in selective development of connections from the open eye. Most cells were responsive only to the open eye and the majority of these were orientation selective. These results were similar to, though less severe than, those found in cats reared with monocular deprivation from birth. Monocular deprivation imposed after 4 mo of normal rearing did not produce selective development of connections from the open eye in terms of either ocular dominance or orientation selectivity. In DR(1) cats visual cortical physiology was degraded in comparison to dark-reared cats after the rearing period. Most cells were binocularly driven but there was a higher frequency of unresponsive cells and a reduced frequency of orientation-selective cells. Subsequent monocular deprivation resulted in a further decrease in the number of binocularly driven cells and an increase in unresponsive cells. However, it did not produce a bias in favor of the open eye in terms of either ocular dominance or orientation selectivity. In DR(2) cats there was a high incidence of unresponsive cells and a marked loss of binocularly driven cells after the rearing period. Subsequent monocular deprivation failed to produce any significant changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗