Biomedical subjects

N Daw

Publications and source records attributed to N Daw.

7 recordsLinked to original sources

PubMed1992

The effect of visual experience on development of NMDA receptor synaptic transmission in kitten visual cortex.

We have studied the effect of dark rearing on the development of excitatory amino acid transmission in 6-week-old kittens. In normal kittens, the NMDA component of the visual response decreases between 3 and 6 weeks of age for cells located in layers IV, V, and VI (Fox et al., 1991). Dark rearing to 6 weeks of age prevents this decrease. Subsequent exposure to light allows the decrease to proceed. Ten days in the light after 6 weeks in the dark was sufficient to decrease the NMDA component of the visual response to the same levels seen in light-reared animals of the same age. Comparison of the effect of the non-NMDA antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione with the NMDA antagonist aminophosphonovalerate showed that the changes were due to the relative contributions of NMDA and non-NMDA receptors to the visual response rather than the overall contribution of glutamate receptors. We also studied the receptive field properties of the cells in the various groups of kittens. Cells given 4 d in the light after 6 weeks in the dark showed increased direction selectivity but little change in response firing rate. After 10 d in the light, visual responses did show some recovery toward adult values, but neither average firing rates nor the proportion of direction-selective cells reached the levels found in normal 6-week-old animals, contrary to the suggestion that a short period in the light can reverse the effect of dark rearing completely. These results show that the decrease in the NMDA component of the visual response seen during normal development of the cortex is caused by visual experience. Changes in NMDA receptors and developmental events such as geniculocortical afferent segregation and acquisition of orientation tuning covary as a function of visual experience rather than age, strongly suggesting that NMDA receptors are involved in experience-dependent developmental processes.

2-Amino-5-phosphonovalerate↗

PubMed1991

The effect of age on binding of MK-801 in the cat visual cortex.

We have examined the effect of age on the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801) in the cat visual cortex. We hypothesized that this binding might change with age because: (1) MK-801 binds to a site associated with the N-methyl-D-aspartate (NMDA) receptor; (2) the NMDA receptor complex has been implicated in neural plasticity; (3) plasticity in the cat visual cortex is age dependent. We used standard receptor binding techniques to measure MK-801 binding in membrane homogenates in cats aged 7 days (d), 21 d, 43 d, 83 d, 7-8 months (mo) and over 2 years. Glutamate (100 microM), glycine (30 microM) and spermidine (20 microM) were used to enhance binding. We found that MK-801 binding is maximal at about 6 weeks of age, decreases slightly by 83 days and then decreases more dramatically in adults. Saturation analysis showed that the of binding with age resulted from variation in number of binding sites and not from variation in affinity. The ability of Mg2+ to inhibit MK-801 binding did not change with age. Dark rearing did not alter the development of MK-801 binding sites.

Aging↗

PubMed1991

Dark-rearing delays the loss of NMDA-receptor function in kitten visual cortex.

Some features of the visual cortex develop postnatally in mammals. For example, geniculocortical axons that initially overlap throughout cortical layer IV segregate postnatally into two sets of interleaved eye-specific bands. NMDA (N-methyl-D-aspartate) receptors are necessary for eye-specific axon-segregation in the frog tectum, and as NMDA receptors play a greater part in synaptic transmission in early life and decrease in function during the period of axon segregation, they may be involved in the segregation of geniculocortical axons: they are well placed to do so as they transduce retinally derived signals essential for segregation. Rearing animals in the dark in early life delays segregation and prolongs the critical period for plasticity. We now report that dark-rearing of kittens also delays the loss of NMDA receptor function in the visual cortex, supporting the view that they play an important part in neuronal development and plasticity.

2-Amino-5-phosphonovalerate↗

PubMed1990

GAP-43 in the cat visual cortex during postnatal development.

GAP-43 levels have been determined by immunoassay in cat visual cortex during postnatal development to test the idea that GAP-43 expression could be related to the duration of the critical period for plasticity. For comparison, GAP-43 levels have also been assayed in primary motor cortex, primary somatosensory cortex, and cerebellum at each age. GAP-43 levels were high in all regions at 5 d (with concentrations ranging from 7-10 ng/microgram protein) and then declined 60-80% by 60 d of age. After 60 d of age, GAP-43 concentrations in each region continued a slow decline to adult values, which ranged from 0.5-2 ng/microgram protein. To test for the involvement of GAP-43 in ocular dominance plasticity during the critical period, the effect of visual deprivation on GAP-43 levels was investigated. Monocular deprivation for 2-7 d, ending at either 27 or 35 d of age, had no effect on total membrane levels of GAP-43. The concentrations of membrane-associated GAP-43 prior to 40 d of age correlate with events that occur during postnatal development of the cat visual cortex. However, the slow decline in membrane-associated GAP-43 levels after 40 d of age may be an index of relative plasticity remaining after the peak of the critical period.

Aging↗

PubMed1990

The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex.

1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1989

A GAP-43-like protein in cat visual cortex.

We have purified a protein that changes in relative concentration during the development of the kitten visual cortex. It resembles GAP-43 (a neuronal protein that is expressed at elevated levels during periods of development and regenerative axon growth) in the following respects: (1) it is an acidic protein (pI = 4.7) whose electrophoretic mobility on SDS-PAGE is similar to, but lower than rat GAP-43, suggesting that the cat protein is larger; (2) its electrophoretic mobility varies with the acrylamide concentration in a manner that is characteristic of GAP-43; (3) its concentration in kitten forebrain is elevated during early postnatal development; (4) the sequence of ten consecutive amino acids from a chemically generated fragment matches the expected sequence from GAP-43; and (5) its amino-acid content also matches GAP-43. We conclude that our purified protein is cat GAP-43. Immunoblots with an antibody prepared against rat GAP-43 suggested that the concentration of GAP-43 in the visual cortex declines with age.

Acrylamide↗

PubMed1989

The location and function of NMDA receptors in cat and kitten visual cortex.

The role of N-methyl-D-aspartate (NMDA) receptors in cat visual cortex was studied as a function of both layer and age by iontophoresis of the NMDA antagonist (D)-2-amino-5-phosphonovaleric acid (APV). Effects on both visual responses and spontaneous activity were observed. In superficial layers (II and III), D-APV reduced visual responses substantially at all ages. Iontophoresis of D-APV with 10 nA of ejecting current for 2-3 min was sufficient to reduce the response to approximately one third of control levels. The magnitude of the reduction did not vary with age. In granular and deep layers (IV, V, and VI), D-APV affected the visual response in young animals but only spontaneous activity in older animals. On average, visual responses were reduced to about half at 20-23 days of age and to about 75% at 4 weeks of age but in most cases were not significantly affected in adults. The rapid change in the functional effect of NMDA receptors over the third and fourth week in granular and deep layers suggests a role in development. There was a reasonable age correlation between the change in effect and the period of geniculocortical afferent segregation. Further experiments will be necessary to determine whether NMDA receptors are necessary for segregation to occur. The presence of an NMDA component to the visual response in the adult in layers II and III argues either that these layers retain some form of plasticity in the adult or that NMDA receptors play a role in the transmission of normal visual input to these layers.

2-Amino-5-phosphonovalerate↗