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N W Daw

Publications and source records attributed to N W Daw.

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

Role of metabotropic glutamate receptors in the cat's visual cortex during development.

We have studied the effect of metabotropic glutamate receptors on the second messenger cAMP, and how it varies with age in light- and dark-reared cats; the overall level of the metabotropic glutamate receptors mGluR1, 2/3, and 5 during development; the laminar distribution of these receptors; and how the physiological effect of the metabotropic glutamate receptor agonist ACPD varies with layer. The increase in cAMP produced by ACPD correlates well with the critical period for ocular dominance plasticity in both light- and dark-reared animals. Basal levels of cAMP also correlate well, but overall levels of mGluRs do not. Thus, the second messenger is likely to be the critical factor in plasticity, rather than the mGluRs. Both group I mGluRs (1 and 5) and group II mGluRs (2 and 3) contribute to the increase in cAMP. However, mGluR5 is affected by rearing in the dark, while mGluR1 is not. Moreover, the laminar distribution of mGluRs 2/3 and 5 changes with age, while mGluR1 does not. The laminar distribution is correlated with the functional effect of ACPD, which varies with layer. In upper layers, ACPD has a depressive effect on both visual response and spontaneous activity, while in lower layers it has a depressive effect on visual response and a facilitatory effect on spontaneous activity. These variations in functional effect with layer need to be taken into account before the role of metabotropic glutamate receptors in development will be fully understood.

Animals↗
PubMed1996

Glycine at the NMDA receptor in cat visual cortex: saturation and changes with age.

1. Saturation of the glycine site at the N-methyl-D-aspartate (NMDA) receptor in cat visual cortex was tested by iontophoresing D-serine, and the contribution of this site to the visual response was tested by iontophoresing 7-chlorokynurenic acid (7-Cl-KYNA). Animals were tested at ages 3 wk, 6 wk, 5 mo, and adult. 2. In at least 40% of cells (24/57), D-serine increased the response significantly, showing that the glycine site was not saturated. However, the increase was rarely > 100%. 3. The amount by which D-serine increased the response did not vary significantly with age. 4. In five cases there was positive evidence for saturation of the glycine site. D-Serine did not increase the response significantly; however, when D-serine was applied on top of 7-Cl-KYNA, it did increase the response compared with that seen with 7-Cl-KYNA alone. These cases were all in 3-wk-old animals. In other cases (28/57), D-serine did not increase the response significantly, but we could not be absolutely certain that the D-serine had reached the site of action. 5. The effect of 7-Cl-KYNA was largest in 3-wk animals, in agreement with previous findings that the effect of D-2-amino-5-phosphonovalerate (APV) is largest at this age. 6. These results may provide a small part of the explanation for the finding that the NMDA receptor-mediated component of the visual response decreases between 3 and 6 wk of age, while the number of NMDA receptors is increasing. However, the magnitude of the results make it likely that other factors are more important.

Aging↗
PubMed1996

Metabotropic glutamate receptors potentiate responses to NMDA and AMPA from layer V cells in rat visual cortex.

1. With the use of whole cell recordings of layer V cells from slices of rat visual cortex, we demonstrate a potentiation of the response to N-methyl-D-aspartate (NMDA) by the metabotropic glutamate agonist (1S,3R)-1-Amino-1,3-cyclopentanedicarboxylic acid. This potentiation occurs within a few seconds and lasts a few minutes. 2. The potentiation is seen with tetrodotoxin in the perfusion solution, but is abolished by guanosine 5'-O-(2-thiodiphosphate) in the pipette solution, showing that it is a postsynaptic phenomenon. The potentiation is also abolished by alpha-methyl-4-carboxyphenylglycine in the bath solution, confirming that it is due to metabotropic glutamate receptors. 3. In 29 of 31 cases tested, the response to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid was also potentiated, and the potentiation remained in the presence of the NMDA antagonist D-2-amino-5-phosphonovalerate.

Animals↗
PubMed1995

Dark-rearing changes dendritic microtubule-associated protein 2 (MAP2) but not subplate neurons in cat visual cortex.

Sensory-dependent modification of cortical morphology is one component of the cortical plasticity that occurs during the critical period for ocular dominance changes. In this study, we used dark-rearing to examine the sensory dependency of subplate neuron death and the quantity of microtubule-associate protein 2 (MAP2)-positive dendrites. Kittens reared in total darkness until the peak of the critical period had fewer laterally extended MAP2-positive dendrites than age-matched normal kittens. This reduction was found in layer IV but not in layer V. Subsequent exposure to light for 10 days after dark-rearing was sufficient to bring the number of MAP2-positive dendrites to the normal level. Contrarily, dark-rearing did not prevent subplate neurons from dying. Exposure to light after dark-rearing did not increase the number of potential dying neurons. These results show that the quantity of MAP2-positive dendrites is sensory-dependent; however, the death of the subplate neurons is not. Therefore, the death of subplate neurons is probably not directly involved in sensory-dependent modifications of synaptic connections. The possible involvement of laterally extended MAP2-dendrites in visual plasticity is discussed.

Age Factors↗
PubMed1995

Immunohistochemical study of two phosphoinositide-linked metabotropic glutamate receptors (mGluR1 alpha and mGluR5) in the cat visual cortex before, during, and after the peak of the critical period for eye-specific connections.

The distribution of two phosphoinositide-linked metabotropic glutamate receptors (mGluR1 alpha and mGluR5) was studied immunohistochemically in area 17 before, during and after the peak of use-dependent modification of eye-specific connections. In the adult, mGluR1 alpha immunoreactivity is high in all layers except layer IV, where mGluR5 immunoreactivity is concentrated. This difference in distribution indicates different functions for these two receptor subtypes. The laminar pattern of mGluR1 alpha immunoreactivity is similar in all three ages, but the overall labeling intensity decreases after the peak (6 weeks of age) of the critical period. The laminar pattern of mGluR5 immunoreactivity changes with age. It is expressed in most layers at 2 days of age and is found mainly in layer IV in the adult. This laminar distribution and developmental pattern match the distribution and the development of the geniculocortical terminals. The change in mGluR1 alpha labeling intensity and mGluR5 laminar distribution over time is consistent with both of these mGluRs being involved in sensory-dependent plasticity for eye-specific connections in the visual cortex.

Animals↗
PubMed1995

Factors that are critical for plasticity in the visual cortex.

Factors that may be critical for plasticity in the visual cortex are evaluated according to three criteria. (1) Do antagonists to the factor abolish plasticity? (2) Does the concentration or activity of the factor peak with the critical period for plasticity? (3) Does rearing in the dark, which postpones the critical period, affect the factor in a similar fashion? N-methyl-D-aspartate receptors fulfil all three criteria. Metabotropic glutamate receptors fulfil two of them. Most other putative factors do not fulfil more than one.

Animals↗
PubMed1994

NMDA receptors in layers II and III of rat cerebral cortex.

Glutamate receptors are found in all layers of the cerebral cortex, but NMDA receptors are concentrated in layers II and III in the adult. We investigated the location of these receptors, and their contribution to the responses of cells in layers V and VI, by iontophoresing NMDA at various distances from the cell body along the apical dendrite of the cells, first in artificial CSF, then in TTX to abolish action potentials. Comparison of responses at various distances along the apical dendrite showed that the response generally increases as distance from the cell body decreases. Comparison of responses in layers II and III, before and after TTX, showed that TTX reduced the response considerably. We conclude first that NMDA receptors in layers II and III are located primarily on cells in layers II and III, rather than on the apical dendrites of cells in layers V and VI, and second that the contribution of NMDA receptors to the response of cells in layers V and VI comes primarily from receptors close to the cell body.

Animals↗
PubMed1994

Effect of longer periods of dark rearing on NMDA receptors in cat visual cortex.

1. Cats were reared in the dark to 3, 5, and 11 mo. We studied the N-methyl-D-aspartate (NMDA) receptor contribution to the visual response in the cortex, defined as the percentage reduction in visual response after application of 2-amino-5-phosphonovaleric acid (APV). We also studied the firing rate in response to the optimal visual stimulus and the spontaneous activity. We made comparisons of all these properties between light-reared and dark-reared animals. 2. The NMDA receptor contribution to the visual response in layers IV, V, and VI of dark-reared animals was substantially above that in light-reared animals at all ages tested. 3. The specificity of receptive field properties in dark-reared animals showed some degeneration between 6 wk and 3 mo of age. At > or = 3 mo, almost no cells were specific for orientation and direction of movement. 4. Firing rate was lower in dark-reared animals at all ages, suggesting a decrease in excitatory drive to the visual cortex. 5. Spontaneous activity was equal in dark- and light-reared animals, suggesting that the overall level of activity (including visual responses as well as spontaneous activity) in light-reared animals is higher than in dark-reared animals. This should tend to upregulate glutamate receptors in general in dark-reared animals.

2-Amino-5-phosphonovalerate↗
PubMed1993

Do NMDA receptors have a critical function in visual cortical plasticity?

The theoretical framework, by which we understand the function of NMDA receptors, is derived, in large part, from work conducted on the hippocampal slice preparation, where NMDA receptors are crucial for a form of synaptic plasticity known as long-term potentiation (LTP). Establishing their role in plasticity mechanisms in the neocortex is proving to be far more difficult than originally envisaged, in part due to the fact that the operation of NMDA receptors is different in the intact animal than in vitro. For example, NMDA receptors are activated at low levels of sensory input in intact animals but only by high levels of input in slice preparations. Recent results suggest that a re-evaluation of the role of NMDA receptors in neocortical plasticity is required. Here we discuss some of the issues and introduce four criteria by which any factor supposedly involved in plasticity can be judged. NMDA receptors fulfill more of these criteria than any of the other factors so far investigated in the visual cortex, but maybe this is because they have been studied more intensively.

Animals↗
PubMed1993

The role of NMDA receptors in information processing.

In this review, we have concentrated on the parallels between the cellular properties of the NMDA receptor and a variety of functional properties within sensory and motor systems. Of course, the NMDA channel exists within the cell in conjunction with a variety of other channels, including non-NMDA channels. Although the NMDA receptor is unique in a cellular sense--it is the only ligand-gated channel that is also voltage dependent and calcium permeable--it is not unique in a functional sense. A cell that has non-NMDA receptors and voltage-sensitive channels will also exhibit nonlinear behavior. Moreover, Buhrle & Sonnhof (1983) demonstrated some time ago that calcium flows into frog motor neurons through more than one type of calcium channel. The contribution to the inflow of calcium from NMDA channels may vary from cell to cell and could easily be a minor proportion of the total. Many authors have pointed out that the NMDA channel has a low conductance at a resting potential of -70 mV. However, many cells in the nervous system are depolarized from -70 mV by excitatory input. Thus, as pointed out above. NMDA receptors make a contribution to the tonic or spontaneous activity of cells in both visual cortex and spinal cord. In practice, many cells are probably working in a range of membrane potentials where the NMDA channels are always open to some extent. Even in the hippocampal slice where a substantial amount of afferent input is removed, NMDA receptors contribute to spontaneous activity (Sah et al 1989). Does the NMDA receptor act as a switch? Does it act as an AND gate? The suggestion that it may act as a switch comes from work on LTP in the hippocampus, which is readily produced by high-frequency stimulation and is abolished by APV. However, activation of the NMDA receptor is only the first in a sequence of reactions leading to LTP: In theory, switch-like behavior could also be produced by calcium-buffering systems within dendritic spines, or by enzymatic processes (Lisman 1985; Zador et al 1990). Fox & Daw (1992) have modeled the action of NMDA and non-NMDA receptors that are activated in parallel with each other, and shown that the occurrence of switch-like behavior depends on the relative density of NMDA versus non-NMDA receptors. Switch-like behavior is not seen in the visual cortex, but might be seen in the hippocampus if the relative density of NMDA receptors there was higher than in the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Critical period for monocular deprivation in the cat visual cortex.

1. Cats were monocularly deprived for 3 mo starting at 8-9 mo, 12 mo, 15 mo, and several years of age. Single cells were recorded in both visual cortexes of each cat, and the ocular dominance and layer determined for each cell. Ocular dominance histograms were then constructed for layers II/III, IV, and V/VI for each group of animals. 2. There was a statistically significant shift in the ocular dominance for cells in layers II/III and V/VI for the animals deprived between 8-9 and 11-12 mo of age. There was a small but not statistically significant shift for cells in layer IV from the animals deprived between 8-9 and 11-12 mo of age, and for cells in layers V/VI from the animals deprived between 15 and 18 mo of age. There was no noticeable shift in ocular dominance for any other layers in any other group of animals. 3. We conclude that the critical period for monocular deprivation is finally over at approximately 1 yr of age for extragranular layers (layers II, III, V, and VI) in visual cortex of the cat.

Aging↗
PubMed1991

An intracellular recording study of stimulus-specific response properties in cat area 17.

Stimulus-specific response properties, such as direction or orientation selectivity, were studied intracellularly in cells recorded from area 17 of the cat. In all 5 direction selective complex cells and one orientation selective simple cell successfully studied, visually evoked excitatory postsynaptic potentials (EPSPs) were tuned to the preferred direction or orientation. Visually evoked inhibitory postsynaptic potentials (IPSPs) were also tuned to the preferred direction/orientation of stimulus. IPSPs evoked by the non-preferred stimulus when present were smaller than those evoked by the preferred stimulus. IPSPs were undetected in two of the 5 cells tested. These results suggest that directionally/orientationally tuned EPSPs make a major contribution to stimulus specificity in visual cortical neurons but IPSPs evoked by a stimulus with null-direction/orientation may sharpen the stimulus specificity.

Animals↗
PubMed1991

Cortisol reduces plasticity in the kitten visual cortex.

We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5-1 microgram/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3-5 months of age does not seem to be due to a rise in cortisol levels during this time.

2-Amino-5-phosphonovalerate↗
PubMed1990

Rod pathways in mammalian retinae.

A variety of recent experiments has resolved the way in which signals are transmitted from rod photoreceptors to ganglion cells in the mammalian retina. Rods connect to a single class of rod bipolar cell, which depolarize in response to light. Rod bipolar cells are not connected directly to ganglion cells: they synapse onto rod amacrine cells, which excite ON-centre ganglion cells via gap junctions, and inhibit OFF-centre ganglion cells via inhibitory glycine synapses. Monoamines have particular influences on the rod system, through synapses with rod amacrine and rod bipolar cells, and a function for dopamine and indoleamines within this system can be hypothesized from recent experiments. There is evidence to suggest that dopaminergic amacrine cells bring the surround response into the rod system through synapses with the rod amacrine cell, and that an indoleamine, probably serotonin, increases the signal in the ON pathway through a feedback synapse onto the rod bipolar terminal.

Animals↗
PubMed1989

Identification and localization of 5-hydroxytryptamine receptor sites in macaque visual cortex.

The two main receptor subtypes for 5-hydroxytryptamine (5HT) were measured and localized in visual cortical areas of macaque monkey. [3H]5HT was used to label all 5HT-1 receptor subtypes and [3H]ketanserin was used to label 5HT-2 receptors. Both receptor types could be demonstrated in membranes prepared from macaque primary visual cortex. The specificity of these ligands for 5HT-1 or 5HT-2 receptors was demonstrated by the pharmacological profile of inhibitors of the specific binding. 5HT-1A receptor sites were detected by displacement experiments and by direct labeling with [3H]8-hydroxy-2(di-n-propylamino) tetralin 8OH-DPAT. Receptor autoradiography showed that the distribution of these receptor subtypes varied from one part of visual cortex to another. 5HT-1 receptors, labeled with [3H]5HT were present in several bands through layer IV of primary visual cortex with the densest band seen in and above layer IVA: another band was in lower layer VI. The band in layer VI was predominantly 5HT-1A sites. There were two main bands of 5HT-2 receptor sites, the most prominent around the IV/V boundary, and the other extending from layer IVA upwards. Adjacent areas showed 5HT receptors in a broad band corresponding to layer IV. 5HT-1A sites were found in superficial layers of adjacent areas, except V2. These layering patterns did not correspond precisely with cytoarchitectonic layering, nor with the pattern of 5HT-containing presynaptic fibres in published reports. It is important, therefore, in considering the role of the 5HT-containing neurons in cortical function to take account not only of the anatomy of the presynaptic terminals, but also of the postsynaptic receptors upon which the released transmitter will act, and their location within the cortex.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Effect of electrical stimulation of locus coeruleus on the activity of neurons in the cat visual cortex.

1. We studied the effect of electrically stimulating the locus coeruleus (LC) and iontophoresing noradrenergic antagonists on visual responses and spontaneous activity of individual cells in the cat primary visual cortex. 2. A bilateral projection from LC to visual cortex was demonstrated anatomically, by retrograde labeling using horseradish peroxidase. Where electrical stimulation of both ipsilateral and contralateral LC affected a cortical neuron, the effect induced by stimulating each side was similar. 3. One hundred and two cells were recorded in area 17: 52% of them had their activity suppressed and 36% had their activity facilitated by LC stimulation. The suppressive effect was predominant in cortical layers II + III and IV, whereas most cells in layer V and one-half of the cells in layer VI were facilitated by LC stimulation. This suggests that LC neurons innervate each cortical layer in a different manner. 4. Simple and complex cells were equally sensitive to LC stimulation. For simple cells, the suppressive effect of LC stimulation was dominant throughout all layers. For complex cells, the suppressive effect was dominant in layers II + III and IV, whereas the facilitatory effect was dominant in layers V and VI. 5. The suppressive effect of LC stimulation was blocked by iontophoretic application of beta-adrenergic receptor antagonists and the facilitatory effect was blocked by either alpha- or beta-adrenergic receptor antagonists. 6. Nonselective alpha-, and selective alpha 1- and alpha 2-receptor antagonists suppressed visual and spontaneous activity in almost all neurons tested, suggesting that these receptors are either facilitatory at a postsynaptic site or inhibitory at a site presynaptic to an inhibitory synapse in the visual cortex. 7. beta-Receptor antagonists facilitated activity in 45% and suppressed activity in 36% of the cells tested, suggesting there are both suppressive and facilitatory types of beta-receptors. 8. The effectiveness of alpha- and beta-antagonists on the activity of neurons without LC stimulation also suggested that spontaneously released noradrenaline activated noradrenergic receptors in the visual cortex even in the anesthetized and paralyzed cat. 9. In most cells tested, both alpha- and beta-receptor antagonists exerted effects on single neurons suggesting that endogenous noradrenaline acts on both alpha- and beta-receptors on the same cell. 10. The activation of LC did not improve the signal- (visual response)to-noise (spontaneous discharge) ratio of neurons in the visual cortex. 11. LC seemed to control the activity of each cortical layer differently, by activating different kinds of noradrenergic receptors in different layers.

Adrenergic alpha-Antagonists↗