Biomedical subjects

R S Zukin

Publications and source records attributed to R S Zukin.

At least 19 recordsLinked to original sources

PubMed1995

Alternatively spliced isoforms of the NMDARI receptor subunit.

Molecularly diverse forms of the NMDA-receptor subunit NRI are formed by alternative RNA splicing. Differential splicing of three exons generates as many as eight NRI splice variants, seven of which have been identified in cDNA libraries. The alternatively spliced exons encode a 21 amino acid sequence in the N-terminus domain (termed NI), and adjacent sequences of 37 and 38 amino acids in the C-terminus domain (termed C1 and C2, respectively). Splicing out the exon segment that encodes the C2 cassette removes the first stop codon, resulting in a new open reading frame that encodes an unrelated sequence of 22 amino acids (C2') before a second stop codon is reached. Differential RNA splicing alters the structural, physiological and pharmacological properties of receptors that comprise NRI subunits. Diversity of NMDA receptors is also caused by differential association with members of the NR2 gene family. The finding of cell-specific expression and developmental regulation of NRI splice variants, and of the NR2 subunits, provides an explanation for the diversity of properties of NMDA receptors in different neuronal populations.

Amino Acid Sequence↗

PubMed1994

Maturation and segregation of brain networks that modify seizures.

The mature brain is less susceptible to seizures than the immature brain. We demonstrate that in the mature substantia nigra (SN) there are two topographically discrete GABAA-sensitive regions which differ in the amount of mRNA expression of the GABAA receptor alpha 1 subunit. These two regions mediate separate anticonvulsant and proconvulsant effects and use divergent projection networks. By contrast, in the immature SN there is no special topography of mRNA expression of the alpha 1 subunit and only the proconvulsant network is present. The decreased seizure susceptibility of the mature brain may be related to postnatal segregation of GABAA-sensitive networks.

Animals↗

PubMed1994

Spermine potentiation of recombinant N-methyl-D-aspartate receptors is affected by subunit composition.

The present study shows that both the NR1 and NR2 subunits critically affect spermine potentiation of heteromeric recombinant N-methyl-D-aspartate receptors. NR1(011), the most prominent NR1 splice variant in rat forebrain, and NR1(100), prominent in midbrain, were expressed in Xenopus oocytes singly and in combination with NR2A, NR2B, and NR2C subunits. As for NR1(011) homomers, NR1(011)/NR2B receptors exhibited spermine potentiation by two mechanisms: by increasing glycine affinity and by increasing current through receptors with bound N-methyl-D-aspartate and glycine. NR1(011)/NR2A receptors exhibited only the increase in glycine affinity, and NR1(011)/NR2C receptors exhibited neither. As for NR1(100) homomers, NR1(100)/NR2B and NR1(100)/NR2A receptors exhibited spermine potentiation only by increasing the glycine affinity. Spermine produced no potentiation of NR1(100)/NR2C receptors. Thus, the NR2B subunit "permits" both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and th NR2C subunit permits neither form of potentiation. Spermine actions on NR1/NR2 showed little voltage dependence. These observations are of interest because the NR1 and NR2 subunits are differentially distributed and developmentally regulated. At early postnatal ages, NR2B subunit mRNA was more highly expressed than NR2A and NR2C mRNAs in hippocampus, neocortex, and caudate-putamen. These findings account for many of the observed differences among neurons in polyamine actions and suggest that these actions will vary in a cell-specific and age-related manner.

Alternative Splicing↗

PubMed1994

AMPA/kainate receptor gene expression in normal and Alzheimer's disease hippocampus.

Alzheimer's disease is a progressive dementia characterized by pronounced degeneration of certain populations of neurons in the hippocampus and cerebral cortex of the brain. One theory is that glutamate receptor-mediated toxicity plays a role in cell loss associated with Alzheimer's disease. We used in situ hybridization to examine GluR1, GluR2, and GluR3 messengerRNAs (encoding alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptor subunits) in sections of autopsy samples of Alzheimer's disease brains and age-, sex-, and post-mortem delay-matched brains from non-demented (control) subjects. GluR1 and GluR2 exhibited a heterogeneous distribution in control brain. GluR1 was expressed in granule cells of the dentate gyrus, in pyramidal cells of the CA1 and CA3 hippocampal subfields and in neurons of the subiculum and entorhinal cortex. GluR2 mRNA was at high density in the dentate gyrus and in CA3, but was at low density in CA1, subiculum, and entorhinal cortex. GluR3 hybridization was at very low levels but selectively localized to the dentate gyrus and CA3. In cerebellum, GluR1 was found in granule and Purkinje cell layers. In sections from Alzheimer's disease brain, a high degree of intersubject variability was observed: some samples showed markedly reduced GluR1 mRNA levels in dentate gyrus, CA1 and CA3 relative to controls; others showed no changes. Microscopic observation of emulsion-dipped sections revealed that the reduction of GluR1 seen in the dentate gyrus and CA3 of some Alzheimer's disease subjects was not due to cell loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Mutagenesis rescues spermine and Zn2+ potentiation of recombinant NMDA receptors.

Alternative splicing generates distinct forms of the NMDA receptor subunit NR1. NR1 subunits with an N-terminal insert (termed N1) form receptors in Xenopus oocytes with greatly reduced potentiation by spermine and Zn2+. Oocytes expressing NR1 receptors with N1 exhibited larger NMDA currents than oocytes expressing corresponding receptors without N1. In the present study, we used mutational analysis to investigate structural features of the N1 insert that control current amplitude and spermine and Zn2+ potentiation. Neutralization of positive charges in N1 rescued spermine and Zn2+ potentiation. Positive charges in N1 did not affect spermine or Zn2+ affinity. Neutralization of positive charges in N1 diminished the responses to the level of NR1 receptors lacking N1. The positively charged N1 may increase NMDA currents by causing a conformational change similar to that produced by spermine and Zn2+ in NR1 receptors lacking N1.

Amino Acid Sequence↗

PubMed1994

NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists.

Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ permeability, is preferentially reduced in CA1 at a time point preceding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), protects CA1 neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor antagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but were unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modification of GluR2 expression changes.

Animals↗

PubMed1994

Glutamate receptor gene expression in spinal cord of arthritic rats.

Injury to peripheral tissue leads to hyperalgesia that appears to be partly mediated by functional changes at the level of the spinal cord. Glutamate receptors are thought to play a role in acute and short-term (minutes to hours) spinal cord nociceptive responses and may be involved in prolonged or chronic pain (hours to days). We used in situ hybridization to examine AMPA/kainate (GluR1, GluR2, and GluR3) and NMDA (NR1) receptor gene expression in spinal cord following induction of prolonged inflammation by a unilateral intraarticular injection of lipopolysaccharide (LPS; 10 micrograms) into the hindpaw. In control rats, GluR1 expression was prominent throughout the layers of the gray matter of the spinal cord. Microscopic examination revealed labeling of neuronal cell somata in all major nuclei. GluR2 was abundant in substantia gelatinosa and motor nuclei; emulsion-dipped sections exhibited intense labeling over densely packed neurons in the superficial laminae of dorsal horn and individual motoneurons of ventral horn. GluR3 and NR1 were expressed at low levels throughout spinal cord gray matter. One day after LPS injection, when joint swelling was maximal, GluR1 expression was bilaterally decreased by 25% in the substantia gelatinosa at the level of the lumbar cord. In contrast, no significant change was apparent in GluR2, GluR3, or NR1 expression in any nucleus of the cord. At 72 hr after injection, when joint diameter approached control values, all four transcripts were expressed at near control levels. These findings provide evidence for a specific decrease in GluR1 expression in the cord in response to joint inflammation.

Animals↗

PubMed1994

Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study.

In adult rats, intraperitoneal administration of kainic acid, a glutamic acid analog and potent neurotoxin, induces persistent seizure activity that results in electrographic alterations and neuropathology that closely resemble human temporal lobe epilepsy. We used in situ hybridization to identify regions of altered glutamate and GABAA receptor gene expression following kainate-induced status epilepticus. In the CA3/CA4 area, the hippocampal region most vulnerable to neurodegeneration after kainate acid treatment, expression of GluR2 (the AMPA/kainate receptor subunit that limits Ca2+ permeability) and GluR3 was decreased markedly at 12 and 24 hr, times preceding neurodegeneration. These findings raise the possibility that increased formation of Ca(2+)-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABAA alpha 1, subunit was also reduced, indicating a possible decrease in inhibitory transmission, which would also enhance excitotoxicity. GluR1 and NR1 expression was not significantly changed. In the dentate gyrus, a region resistant to neurodegeneration, concomitant increases in GluR2 and GluR3 expression were observed; GluR1, NR1, and GABAA alpha 1 mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABAA alpha 1 expression represented changes in mRNA content per neuron and were specific to pyramidal cells of the CA3/CA4 area and to granule cells of the dentate gyrus. These findings indicate that kainate seizures modify hippocampal glutamate and GABAA receptor expression in a cell-specific manner. Timing of the changes in glutamate and GABAA receptor mRNAs indicates that these changes may play a causal role in hippocampal neuronal cell loss following kainate-induced seizures.

Animals↗

PubMed1993

Serotonergic lesions decrease mu- and delta-opiate receptor binding in discrete areas of the hypothalamus and in the midbrain central gray.

Serotonergic nerve terminals in the brain were lesioned by intraventricular infusion of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and levels of mu- and delta-opiate binding were measured in brain areas implicated in reproductive behavior and gonadotropin secretion. The lesion decreased mu-receptor binding in the preoptic area (mPOA) and the midbrain central gray, while delta-receptor binding was decreased in the mPOA and the dorsomedial nucleus of the hypothalamus. Hypothalamic serotonergic lesions also attenuated morphine inhibition of female sexual behavior. These results indicate the existence of serotonergic-opiate interactions in select regions of the brain and suggest that these interactions may be important in the regulation of lordosis behavior.

Animals↗

PubMed1993

Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C.

The N-methyl-D-aspartate (NMDA) receptor NR1 gene encodes RNA that is alternatively spliced to generate at least seven variants. The variants arise from splicing in or out of three exons; one encodes a 21-amino acid insert in the N-terminal domain, and two encode adjacent sequences of 37 and 38 amino acids in the C-terminal domain. Splicing out of the second C-terminal exon deletes a stop codon and results in an additional open reading frame encoding an unrelated sequence of 22 amino acids before arriving at a second stop codon. We denote the NR1 variants by the presence or absence of the three alternatively spliced exons (from 5' to 3'); thus, NR1(111) has all three exons, NR1(000) has none, and NR1(100) has only the N-terminal exon. We report here electrophysiological characterization of six splice variants of the NR1 receptor expressed in Xenopus oocytes. NR1 receptors that lacked the N-terminal exon (NR1(000), NR1(010), and NR1(011)) exhibited a relatively high affinity for NMDA (EC50 approximately 13 microM) and marked potentiation by spermine. In contrast, those receptor variants with the N-terminal insert (NR1(100), NR1(101), and NR1(111)) showed a lower agonist affinity and little or no spermine potentiation at saturating glycine. All six variants showed spermine potentiation at low glycine and inhibition by spermine at more negative potentials. Variants differing only in the C-terminal domain differed little in agonist affinity and spermine potentiation. These findings indicate that the N-terminal insert either participates in agonist and polyamine binding domains or indirectly modifies their conformations. The splice variants differed in the extent to which they could be potentiated by activators of protein kinase C (PKC) from 3- to 20-fold. Presence of the N-terminal insert and absence of the C-terminal sequences increased potentiation by PKC. These findings identify the contributions of the separate polypeptide domains to modulation by polyamines and PKC and provide further support for the concept that subunit composition determines functional properties of NMDA receptors.

Alternative Splicing↗

PubMed1993

Effects of polyamines on NMDA-induced currents in rat hippocampal neurons: a whole-cell and single-channel study.

Actions of the polyamines spermine and spermidine on NMDA-induced currents were examined in cultured hippocampal neurons from embryonic rat. In whole-cell patch experiments using voltage-clamp, spermine (300 microM) produced about a two-fold potentiation of responses to NMDA (at -70 mV in the presence of saturating glycine); half-maximal potentiation was elicited at 207 microM. The potentiation produced by spermine was somewhat greater at positive potentials. The onset of potentiation was fast (t1/2 < 1 s), indicative of an extracellular site of action. Spermidine was of comparable potency but less efficacious than spermine in potentiating NMDA responses. In excised outside-out patches, spermine exhibited two actions on NMDA-induced single-channel responses. In some patches, it increased the channel open probability; both frequency of channel opening and burst length were increased with no significant change in the mean open duration, which accounted for much of the potentiation seen in whole-cell experiments. In all patches, spermine decreased channel conductance at negative voltages, an effect ascribable to fast channel block (with a possible contribution by charge screening). These results are consistent with opposing actions of polyamines mediated at distinct sites on the NMDA receptor.

Action Potentials↗

PubMed1993

Developmental regulation of mRNAs encoding rat brain kainate/AMPA receptors: a northern analysis study.

Functionally diverse kainate/alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptors are generated by assembly of glutamate receptor (GluR)1, 2, and 3 subunits into homomeric and heteromeric channels. We examined GluR1, 2, and 3 gene expression in embryonic, neonatal, and adult rat brain by northern analysis under conditions of high stringency. In the adult, hybridization to a GluR1 riboprobe revealed the presence of an abundant RNA species, 5.2 kb in size, and minor bands of 3.2 and 3.9 kb. GluR2 hybridized to two species, 3.9 and 5.9 kb, of comparable abundance, presumably attributable to alternate splice products. Hybridization to the GluR3 riboprobe showed a major species of 5.2 kb. This pattern of RNA species was invariant over all the brain regions examined. Examination of GluR expression in development revealed that in the postnatal period, GluR1, 2, and 3 mRNAs are regulated as a function of age. In adult rat brain, GluR1 and 2 mRNA expression was highest in hippocampus; GluR3 was expressed at highest density in hippocampus and frontal cortex. The three transcripts were first detected at embryonic day 16 and then exhibited changes in expression levels in a region-specific manner. In hippocampus, all three transcripts exhibited elevated expression in the late neonatal period; in frontal cortex, elevated expression was observed for GluR2 and 3 only. In striatum, all three transcripts were expressed at relatively low levels throughout development, with a modest peak at postnatal day 14. In cerebellum, the GluR1 mRNA level was high from postnatal day 28 to adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

Molecular biology of PCP and NMDA receptors.

The studies described demonstrate that rat brain mRNA directs the synthesis of at least four types of functional EAA receptors in the Xenopus oocyte system, whereas in this system NCB-20 cell mRNA directs the synthesis of only the NMDA type of EAA receptor. The NMDA channel expressed in the oocyte, using either rat brain mRNA or NCB-20 cell mRNA, exhibits the pharmacologic properties of the neuronal receptor, including the functional association with the PCP receptor located within the NMDA-gated channel. The demonstration that mRNA isolated from NCB-20 cells lacking functional NMDA-activated channels, but bearing PCP binding sites, can encode functional NMDA-activated channels in the oocyte indicates some defect or regulating step in posttranslational processing or insertion of the receptors into the plasma membrane in the cell of origin. This is the only cell line known to (1) have PCP receptors that appear to be associated with NMDA receptors and (2) provide a homogeneous, self-replicating population of cells that can be manipulated genetically and by changing the extracellular environment. Consequently, the NCB-20 cell line will be useful for the study of the NMDA receptor and its expression.

Animals↗

PubMed1992

Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats.

Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca(2+)-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death.

Analysis of Variance↗

PubMed1992

Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C.

Molecular cloning identified complementary DNA species, from a rat ventral midbrain library, encoding apparent splice variants of the N-methyl-D-aspartate (NMDA) receptor NMDAR1 (which we now term NR1a). Sequencing revealed that one variant, NR1b, differs from NR1a by the presence of a 21-amino acid insert near the amino end of the N-terminal domain and by an alternate C-terminal domain in which the last 75 amino acids are replaced by an unrelated sequence of 22 amino acids. NR1b is virtually identical to NR1a in the remainder of the N- and C-terminal domains, at the 5' and 3' noncoding ends, and within the predicted transmembrane domains and extracellular and cytoplasmic loops. These findings suggest that the two forms of the receptor arise by differential splicing of a transcript from the same gene. Sequencing of other clones indicates the existence of a third variant, NR1c, identical to NR1b in its C terminus but lacking the N-terminal insert. NR1b RNA injected into Xenopus oocytes generated functional homomeric NMDA channels with electrophysiological properties distinct from those of NR1a homomeric channels. NR1b channels exhibited a lower apparent affinity for NMDA and for glutamate. NR1b channels exhibited a lower affinity for D-2-amino-5-phosphonovaleric acid and a higher affinity for Zn2+. The two receptor variants showed nearly identical affinities for glycine, Mg2+, and phencyclidine. Spermine potentiation of NMDA responses, prominent in oocytes injected with rat forebrain message, was also prominent for NR1a receptors, but was greatly reduced or absent for NR1b receptors. Treatment with the protein kinase C activator phorbol 12-myristate 13-acetate potentiated NMDA responses in NR1b-injected oocytes by about 20-fold; potentiation of NMDA responses in NR1a-injected oocytes was much less, about 4-fold. These findings support a role for alternate splicing in generating NMDA channels with different functional properties.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Are Ca(2+)-permeable kainate/AMPA receptors more abundant in immature brain?

The permeability properties of kainate/AMPA receptors are determined by subunit composition. The GluR1 and GluR3 subunits form Ca(2+)-permeable channels and exhibit inward rectification; heteromeric receptors containing the GluR2 subunit are Ca(2+)-impermeable and electrically linear. These observations raise the possibility of a developmental 'switch' in which turning on or off of GluR2 expression regulates the level of Ca2+ permeable kainate/AMPA receptors. We examined the ratio of GluR1 and GluR3 to GluR2 gene expression in developing and adult rat brain by in situ hybridization. A larger value of this ratio is likely to be associated with greater Ca2+ permeability. Our data suggest that in neocortex, striatum and cerebellum the number of Ca(2+)-permeable kainate/AMPA receptors is high at P4 and declines monotonically with age. In hippocampus, the number increases from P7 to P21, after which it declines. These findings provide evidence for a developmental 'switch' in which Ca2+ permeable glutamate receptors are turned off following early developmental events.

Aging↗

PubMed1991

Neuroanatomical localization of kappa 1 and kappa 2 opioid receptors in rat and guinea pig brain.

The neuroanatomical localization of kappa opioid receptors in rat and guinea pig brain was determined by quantitative in vitro receptor autoradiography. Our study shows striking differences in kappa 1 and kappa 2 receptor distributions both between species and within each species. In the rat brain, kappa 1 sites (labeled by [3H]U-69,593) are of low density and confined to a small number of structures. These include the claustrum, endopiriform nucleus, caudate putamen, nucleus accumbens, midline nuclear group of the thalamus, superficial grey layer of the superior colliculus, and central grey. kappa 2 sites (labeled by [3H]ethylketocyclazocine or [3H]bremazocine under conditions in which mu, delta, and kappa 1 binding was suppressed) are more widely distributed throughout all levels of rat brain. kappa 2 sites occur at high density in the caudate putamen, nucleus accumbens, amygdala, thalamus, and interpeduncular nuclei. In guinea pig brain, kappa 1 sites predominate and are of high density in layers I and VI of the neocortex, claustrum, endopiriform nucleus, caudate putamen, nucleus accumbens, and molecular layer of the cerebellum. As in rat brain, kappa 2 sites in guinea pig are more uniformly and widely distributed throughout the brain than are kappa 1 sites. The highest density of kappa 2 sites is in the dorsal parabrachial nucleus, interpeduncular nuclei, mammillary nuclei, and posterior thalamic nuclei. Results from this study demonstrate important interspecies differences in the distribution of kappa 1 and kappa 2 opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1991

Differential expression of three glutamate receptor genes in developing rat brain: an in situ hybridization study.

Non-N-methyl-D-aspartate glutamate receptors (GluRs) are encoded by a gene family, known members of which are designated GluR-1, -2, -3, -4, and -5. The present study examined the developmental pattern of GluR-1, -2, and -3 gene expression in rat brain. In situ hybridization revealed different spatial patterns throughout the brain for the cognate mRNAs at all ages examined, as well as different temporal patterns during development. In the adult all three mRNAs were expressed prominently in the pyramidal and granule layers of the hippocampus and in the Purkinje cell layer of the cerebellum, where detailed differences were apparent at the cellular level. In neocortex, GluR-2 mRNA exhibited prominent lamination and regional differences, which were less marked for GluR-1 and -3 mRNAs. In caudate-putamen GluR-2 mRNA was at high levels, but GluR-1 and -3 mRNAs were not. At early ages transcripts were transiently elevated relative to adult levels. GluR-1 mRNA reached peak expression in cortex at postnatal day 14 (P14) (225% of adult), in striatum at P4 (255% of adult), in hippocampus at P14 (195% of adult), and in cerebellum at P21 (150% of adult). GluR-3 exhibited more modest peaks in neocortex and hippocampus. In contrast, GluR-2 mRNA was at near adult levels throughout the first days of postnatal life and exhibited a peak only in cerebellum at P14 (168% of adult). The finding of differential developmental regulation of the GluR-1, -2, and -3 genes indicates that the receptors they encode may have different influences on synaptic plasticity, neuronal survival, and susceptibility to excitatory amino acid toxicity.

Aging↗