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N W Daw

Publications and source records attributed to N W Daw.

At least 19 recordsLinked to original sources
PubMed2003

Long term potentiation varies with layer in rat visual cortex.

Long term potentiation (LTP) in various layers of rat visual cortex was studied in 90 cells with visually identified, whole-cell recordings. LTP was induced in layer II/III, layer V or layer VI with theta burst stimulation (TBS), but was not observed in layer IV. In the presence of a NMDA antagonist, D-AP5, in the bath solution, potentiation was blocked in layer II/III, some depression was seen in layer V, and potentiation still remained in layer VI. After addition of a specific mGluR1 antagonist, LY367385, to the bath solution, LTP was reduced in layer II/III and layer V, and was blocked in layer VI. After a specific mGluR5 antagonist, MPEP was applied in the bath solution, LTP was enhanced in layer VI, and blocked in layer V. We conclude that: (1) LTP in layer VI is different from other layers, depending on mGluR1, but not NMDA receptors. (2) In layer II/III, LTP is NMDA-dependent and is not blocked by group I mGluR antagonists. (3) LTP in layer V is both NMDA receptor and mGluR5 receptor-dependent. (4) LTP was not induced in layer IV with TBS.

Animals↗
PubMed2001

Cyclic AMP-dependent protein kinase mediates ocular dominance shifts in cat visual cortex.

Visual experience during a critical period early in postnatal development can change connections within mammalian visual cortex. In a kitten at the peak of the critical period (approximately P28-42), brief monocular deprivation can lead to complete dominance by the open eye, an ocular dominance shift. This process is driven by activity from the eyes, and depends on N-methyl-D-aspartate (NMDA) receptor activation. The components of the intracellular signaling cascade underlying these changes have not all been identified. Here we show that inhibition of protein kinase A (PKA) by Rp-8-Cl-cAMPS blocks ocular dominance shifts that occur following monocular deprivation early in the critical period. Inhibition of protein kinase G by Rp-8-Br-PET-cGMPS had no effect, indicating a specificity for the PKA pathway. Enhancement of PKA activity late in the critical period with Sp-8-Cl-cAMPS did not increase plasticity. PKA is a necessary component of the pathway leading to cortical plasticity during the critical period.

Animals↗
PubMed2001

Effect of the group I metabotropic glutamate agonist DHPG on the visual cortex.

Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3-4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.

Action Potentials↗
PubMed2001

Developmental changes and ocular dominance plasticity in the visual cortex.

There is a shift in ocular dominance of cells recorded in the visual cortex which occurs after closure of one eye during a critical period lasting from eye opening to puberty. Three criteria distinguish factors that are crucially related to ocular dominance plasticity: 1) the factor should be more concentrated or active at the peak of the critical period; 2) dark rearing, which makes the cortex less plastic early in the critical period and more plastic late in the critical period, should have a similar effect on the factor, and 3) antagonists or inhibitors of the factor should block ocular dominance plasticity. The second criterion can be used to distinguish activity-related factors that may simply increase or decrease with development from factors that are more specifically related to plasticity. Two factors currently fulfill these criteria, namely N-methyl-D-asparate (NMDA) receptors and protein kinase A (PKA). PKA and NMDA receptors are linked through calcium, since calcium influx through the NMDA receptor increases the production of cyclic AMP by calcium-sensitive adenylate cyclase, which in turn activates PKA. PKA is specifically involved, since protein kinase G and protein kinase C antagonists do not inhibit ocular dominance plasticity. However, NMDA agonists and PKA activators by themselves are not known to bring back plasticity. Thus there may be two or more pathways for ocular dominance plasticity acting in parallel with each other: for example, metabotropic glutamate receptors may act in parallel with NMDA receptors to change calcium levels within the cell.

Aging↗
PubMed2000

2R,4R-4-Aminopyrrolidine-2,4-dicarboxylate (APDC) attenuates cortical EPSPs.

We studied the effect of the Type II metabotropic glutamate receptor (mGluR 2,3) agonist APDC on the response of neurons in slices of rat visual cortex. In all cortical layers, APDC attenuated the EPSP produced by stimulation of the predominant excitatory input. This EPSP attenuation was seen in both younger and older rat slices and was present with G-protein blockade in the cell recorded, demonstrating that it was a presynaptic effect. Further, this EPSP attenuation was blocked by the mGluR 2,3 antagonist EGLU. A postsynaptic depressive effect of APDC on the NMDA response was seen in layers 2 and 3, but not in layers 5 and 6. Thus, the predominant action of Type II mGluRs in the visual cortex is a presynaptic reduction of glutamate release which persists through development. This regulation may be important in the setting of excitatory tone in visual cortex and in the extraction/processing of visual information.

Animals↗
PubMed1999

Development and function of metabotropic glutamate receptors in cat visual cortex.

Metabotropic glutamate receptors have been implicated in plasticity in the hippocampus and cerebellum. Are they also involved in plasticity in the visual cortex? This is a complicated question because of the diversity of metabotropic glutamate receptors and the variations in both receptors and plasticity with layer. Inhibition driven by group II metabotropic glutamate receptors is certainly correlated with ocular dominance segregation in layer IV of the cortex. Of the group I metabotropic glutamate receptors, mGluR5 may be involved in plasticity, but mGluR1 is unlikely to be. Both group I and group II receptors produce increases in cyclic adenosine monophosphate which are clearly related to plasticity. Further conclusions await the development of agonists and antagonists specific for individual metabotropic glutamate receptors, as opposed to groups of the receptors.

Animals↗
PubMed1999

Injection of MK-801 affects ocular dominance shifts more than visual activity.

Kittens were given intramuscular injections of the N-methyl--aspartate (NMDA) antagonist MK-801 twice daily (morning and midday) during the peak of the period of susceptibility for ocular dominance changes. They were then exposed to light with one eye closed for 4 h after each injection. The ocular dominance of these kittens was shifted significantly less than that of kittens injected with saline and exposed to light over the same period at the same age. After recording a sample of cells for an ocular dominance histogram, the kittens were injected with the same dose of MK-801 that was used during rearing to observe its effect on the activity of single cells in the visual cortex. In the majority of cells (7/13) there was no significant change in activity. Positive evidence for a reduction in activity was seen in only a minority (3/13) of cells. In a separate series of experiments, dose-response curves were measured for cells in the visual cortex in response to iontophoresis of NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and the effect of an injection of MK-801 on these curves was measured. MK-801, at doses similar to those used in the ocular dominance experiments, had a significant effect on the dose-response curves for NMDA, but little effect on the dose-response curves for AMPA, or the visual responses of the cells. We conclude that ocular dominance shifts can be reduced significantly by a treatment that has little effect on the level of activity of cells in the visual cortex but does specifically affect the responses of the cells to NMDA as opposed to the responses to AMPA.

Algorithms↗
PubMed1999

Effect of the group II metabotropic glutamate agonist, 2R,4R-APDC, varies with age, layer, and visual experience in the visual cortex.

Group II metabotropic glutamate receptors (mGluR 2/3) are distributed differentially across the layers of cat visual cortex, and this distribution varies with age. At 3-4 wk, mGluR 2/3 receptor immunoreactivity is present in all layers. By 6-8 wk of age, it is still present in extragranular layers (2, 3, 5, and 6) but has disappeared from layer 4, and dark-rearing postpones the disappearance of Group II receptors from layer 4. We examined the physiological effects of Group II activation, to see if these effects varied similarly. The responses of single neurons in cat primary visual cortex were recorded to visual stimulation, then the effect of iontophoresis of 2R,4R-4 aminopyrrolidine-2, 4-decarboxylate (2R,4R-APDC), a Group II specific agonist, was observed in animals between 3 wk and adulthood. The effect of 2R, 4R-APDC was generally suppressive, reducing both the visual response and spontaneous activity of single neurons. The developmental changes were in agreement with the immunohistochemical results: 2R, 4R-APDC had effects on cells in all layers in animals of 3-4 wk but not in layer 4 of animals >6 wk old. Moreover, the effect of 2R, 4R-APDC was reduced in the cortex of older animals (>22 wk). Dark-rearing animals to 47-54 days maintained the effects of 2R, 4R-APDC in layer 4. The disappearance of Group II mGluRs from layer 4 between 3 and 6 wk of age is correlated with the segregation of ocular dominance columns in that layer, raising the possibility that mGluRs 2/3 are involved in this process.

Aging↗
PubMed1998

The effect of ACPD on the responses to NMDA and AMPA varies with layer in slices of rat visual cortex.

The effect of 1S,3R-aminocyclopentane dicarboxylic acid (ACPD) was measured on cells from various layers in slices of the rat visual cortex using whole-cell recording techniques. The position of the recorded cell was estimated by distance from pia to the layer VI/white matter boundary, and verified in 34/97 cells by staining with biocytin. Potentiation or depression of the responses to NMDA and AMPA by the metabotropic glutamate agonist ACPD was examined by iontophoresis of the drugs close to the cell body. Iontophoresis of ACPD had different effects in different layers. In layer VI, ACPD produced a substantial depolarization, which augmented the responses to NMDA and AMPA. In layer V, ACPD did not produce a significant depolarization, but potentiated the response to NMDA and AMPA. In layer IV, ACPD produced a small hyperpolarization, and depressed the response to NMDA. In layers II and III, the results were small and variable. Most recordings from stained cells were from pyramidal cells. Where recordings from non-pyramidal cells were obtained (3/34), results were the same as from pyramidal cells in the same layer. The same results were obtained when tetrodotoxin was in the bath solution. We conclude that the potentiation or depression of the response to NMDA and AMPA by ACPD varies with layer in rat visual cortex.

Animals↗
PubMed1998

The group III metabotropic glutamate receptor agonist, l-AP4, reduces EPSPs in some layers of rat visual cortex.

The action of the specific Group III metabotropic glutamate receptor, l-2-amino-4-phosphonobutanoic acid (l-AP4) was tested in slices of rat visual cortex. When the predominant input to the cell was stimulated, l-AP4 generally reduced the EPSP that was produced. This result was specific to the layer: it was found when recording cells in layers II/III, V and VI, but not when recording cells in layer IV. The effect was the same when G-proteins in the cell recorded were inactivated. Also, l-AP4 had little effect on membrane potential and input impedance of the cell recorded, and little effect on the response to NMDA in that cell. Thus, Group III metabotropic glutamate receptors act presynaptically to reduce the release of glutamate onto cells in layers II/III, V and VI in visual cortex, but not cells in layer IV.

Alanine↗
PubMed1998

Critical periods and amblyopia.

During the past 20 years, basic science has shown that there are different critical periods for different visual functions during the development of the visual system. Visual functions processed at higher anatomical levels within the system have a later critical period than functions processed at lower levels. This general principle suggests that treatments for amblyopia should be followed in a logical sequence, with treatment for each visual function to be started before its critical period is over. However, critical periods for some visual functions, such as stereopsis, are not yet fully determined, and the optimal treatment is, therefore, unknown. This article summarizes the current extent of our knowledge and points to the gaps that need to be filled.

Adolescent↗
PubMed1997

Developmental and sensory-dependent changes of phosphoinositide-linked metabotropic glutamate receptors.

Metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission, and there is evidence that phosphoinositide (PI)-linked mGluRs may be involved in sensory-dependent plasticity during the development of cat visual cortex. Consequently, we asked the questions: Where are the PI-linked mGluRs (mGluR1alpha and mGluR5) in the visual cortex? Does the quantity and distribution of these receptors change in the cat visual cortex during postnatal development, and are these features sensory-dependent? We found that the quantity of mGluR1alpha decreases with age, whereas the laminar distribution of mGluR1alpha remains the same. Quantity of mGluR5 also decreases, but the laminar distribution of mGluR5 changes during development. The pattern and timing of the mGluR5 change in distribution follow the development of geniculocortical afferents. Immunostaining indicates that reduction of receptor occurs mainly in layers V-VI for mGluR1alpha and outside layer IV for mGluR5. Dark-rearing postpones the laminar change of mGluR5 and produces an increased level of mGluR5 between postnatal 1.5-6 weeks of age but has no significant effect on the mGluR1alpha distribution or the mGluR1alpha quantity. These results suggest that mGluR1alpha and mGluR5 are involved in different aspects of cortical development. The mGluR5 is more likely to be involved in sensory-dependent events than mGluR1alpha. The lack of developmental correlation between mGluR quantities and the critical period for ocular dominance plasticity also suggests that other factors besides mGluR quantities are important for ocular dominance plasticity.

Aging↗
PubMed1996

cAMP levels increased by activation of metabotropic glutamate receptors correlate with visual plasticity.

We have investigated the cAMP level increased by stimulation of metabotropic glutamate receptors (mGluRs) in cat visual cortex during development. The cAMP level increases activated by the general mGluR agonist (1S,3R)-1-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were closely correlated with the critical period for ocular dominance plasticity in both light- and dark-reared animals. Activation of either group I or group II mGluRs increased the cAMP level. Group II mGluR activation also reduced the forskolin-stimulated cAMP increase. The correlation was emulated by a mixture of groups I, II, and III mGluR agonists but not by agonists applied singly; therefore, the correlation is attributable to activation of multiple groups of mGluRs. The cAMP level increased by the mixture was greater than the sum of the increases produced by the agonists applied singly (super-additive effect), suggesting an interaction between the G-proteins and/or second messengers controlled by these mGluRs. The basal cAMP level also correlated closely with the critical period until shortly after the peak of the critical period. Therefore, the major factor that contributes to the correlation between the ACPD-stimulated cAMP increase and the peak of the critical period is the basal level of cAMP: the activation of multiple mGluRs amplifies the basal cAMP. We suggest that both basal activity of cAMP production and activation of mGluRs may be important in plasticity in the visual cortex.

Animal Husbandry↗
PubMed1996

The contribution of NMDA receptors to the visual response in animals that have been partially monocularly deprived.

Kittens were monocularly deprived to give a partial shift in the ocular dominance histograms from their visual cortices. Responses were measured for the normal and deprived eyes at a variety of contrasts, and curves fitted to give measurements of background activity and peak visual response. The N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5-phosphonovalerate (APV) was then applied, and the effect on the contrast-response curves was measured, and compared in the two eyes. In normal animals, the effect of APV on the contrast-response curve was similar in the two eyes. In monocularly deprived animals, on average, peak visual response was affected similarly in the two eyes, although there was wide variability from cell to cell. When the effect of APV on background activity was measured, there was difference between the normal and deprived eyes. APV reduced background activity in the normal eye more than it reduced background activity in the deprived eye. In other words, the NMDA contribution to background activity in the deprived eye was reduced compared to the NMDA contribution to background activity in the normal eye. This could represent a reduction of NMDA receptors in the pathway from the deprived eye, like the reduction of acetylcholine receptors associated with the losing input at the neuromuscular junction before the nerve is eliminated.

2-Amino-5-phosphonovalerate↗
PubMed1996

Inhibition of nitric oxide synthase does not alter ocular dominance shifts in kitten visual cortex.

1. Since nitric oxide has been proposed as a feedback factor in plasticity in the hippocampus, we tested whether it might also be a feedback factor in sensory-dependent plasticity in the cat visual cortex. 2. The effects of monocular deprivation were compared between eight hemispheres with infusion of a nitric oxide synthase inhibitor, and eight control hemispheres with either infusion of the inactive isomer, or no infusion. Although nitric oxide synthase activity was reduced significantly, the ocular dominance histograms were not substantially different in the two groups of animals. We conclude that the feedback factor for sensory-dependent plasticity in the visual cortex is likely to be some factor other than nitric oxide.

Animals↗
PubMed1996

Glutamate receptors and development of the visual cortex: effect of metabotropic agonists on cAMP.

Glutamate receptors are more active in several respects in young animals than in adults. Here we examine the effect of metabotropic glutamate agonists on rat cortical cAMP during and after the critical period for visual cortex plasticity. Quisqualate produced a substantial increase in cAMP, which was larger during the critical period than in the adult. The increase was not affected by CNQX or APV, showing that it was not due to the action of quisqualate on ionotropic glutamate receptors. Both Type I mGluRs (mGluRs 1 and/or 5) and Type II mGluRs (mGluRs 2 and/or 3) probably contributed to the cAMP increase because (i) ACPD and L-CCG-I, which are more active on Type II mGluRs, were more effective than DHPG, which is more active on Type I mGluRs; and (ii) there was a significant difference in the effect of ACPD on the increase in cAMP, comparing mGluR1 knockout mice with control mice. Agonists which produce large stimulation of cAMP production (ACPD, L-CCG-I), as well as L-AP4, also produced small attenuations of forskolin-stimulated cAMP, but only at high concentrations. Thus, we conclude that it is the stimulation and/or potentiation of cAMP production that is significant, rather than the attenuation of forskolin-stimulated cAMP. Since this stimulation and/or potentiation is higher during the critical period than in the adult, and the cAMP second messenger system has been implicated in hippocampal plasticity, it may also play a role in visual cortex plasticity.

Animals↗