Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouse

Glutamate is the primary excitatory neurotransmitter in the brain, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors mediate most fast synaptic transmission. AMPA receptors are tetrameric assemblies composed from four possible subunits (GluR1-4). In hippocampal pyramidal cells, AMPA receptors are heteromeric receptors containing the GluR2 subunit and either GluR1 or GluR3. It is generally accepted that the trafficking of GluR1/GluR2 receptors to synapses requires activity, whereas GluR2/GluR3 receptors traffic constitutively. It has been suggested that the trafficking is governed by the cytoplasmic C termini of the subunits. Because the basis for this theory relied on the introduction of unnatural, homomeric, calcium-permeable AMPA receptors, we have used the GluR2(-/-) knock out mouse to determine whether the expression of mutated forms of GluR2 can rescue WT synaptic responses. We find that GluR2, lacking its entire C terminus, or a GluR2 chimera containing the C terminus of GluR1, is capable of trafficking to the synapse in the absence of activity. These findings suggest that the GluR2 C terminus is not required for GluR2 synaptic insertion.     

Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission

Extracellular signal-regulated kinase (ERK) signaling is important for neuronal synaptic plasticity. We report here that the protein kinase ribosomal S6 kinase (RSK)2, a downstream target of ERK, uses a C-terminal motif to bind several PDZ domain proteins in heterologous systems and in vivo. Different RSK isoforms display distinct specificities in their interactions with PDZ domain proteins. Mutation of the RSK2 PDZ ligand does not inhibit RSK2 activation in intact cells or phosphorylation of peptide substrates by RSK2 in vitro but greatly reduces RSK2 phosphorylation of PDZ domain proteins of the Shank family in heterologous cells. In primary neurons, NMDA receptor (NMDA-R) activation leads to ERK and RSK2 activation and RSK-dependent phosphorylation of transfected Shank3. RSK2-PDZ domain interactions are functionally important for synaptic transmission because neurons expressing kinase-dead RSK2 display a dramatic reduction in frequency of AMPA-type glutamate receptor-mediated miniature excitatory postsynaptic currents, an effect dependent on the PDZ ligand. These results suggest that binding of RSK2 to PDZ domain proteins and phosphorylation of these proteins or their binding partners regulates excitatory synaptic transmission.     

Endocytosis and recycling of AMPA receptors lacking GluR2/3

Excitatory synapses in the mammalian brain contain two types of ligand-gated ion channels: AMPA receptors (AMPARs) and NMDA receptors (NMDARs). AMPARs are responsible for generating excitatory synaptic responses, whereas NMDAR activation triggers long-lasting changes in these responses by modulating the trafficking of AMPARs toward and away from synapses. AMPARs are tetramers composed of four subunits (GluR1-GluR4), which current models suggest govern distinct AMPAR trafficking behavior during synaptic plasticity. Here, we address the roles of GluR2 and GluR3 in controlling the recycling- and activity-dependent endocytosis of AMPARs by using cultured hippocampal neurons prepared from knockout (KO) mice lacking these subunits. We find that synapses and dendritic spines form normally in cells lacking GluR2/3 and that upon NMDAR activation, GluR2/3-lacking AMPARs are endocytosed in a manner indistinguishable from GluR2-containing AMPARs in wild-type (WT) neurons. AMPARs lacking GluR2/3 also recycle to the plasma membrane identically to WT AMPARs. However, because of their permeability to calcium, GluR2-lacking but not WT AMPARs exhibited robust internalization throughout the dendritic tree in response to AMPA application. Dendritic endocytosis of AMPARs also was observed in GABAergic neurons, which express a high proportion of GluR2-lacking AMPARs. These results demonstrate that GluR2 and GluR3 are not required for activity-dependent endocytosis of AMPARs and suggest that the most important property of GluR2 in the context of AMPAR trafficking may be its influence on calcium permeability.     

The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus

Neurotrophins are involved in the modulation of synaptic transmission, including the induction of long-term potentiation (LTP) through the receptor TrkB. Because previous studies have revealed a bidirectional mode of neurotrophin action by virtue of signaling through either the neurotrophin receptor p75NTR or the Trk receptors, we tested the hypothesis that p75NTR is important for longterm depression (LTD) to occur. Although LTP was found to be unaffected in hippocampal slices of two different strains of mice carrying mutations of the p75NTR gene, hippocampal LTD was impaired in both p75NTR-deficient mouse strains. Furthermore, the expression levels of two (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits, GluR2 and GluR3, but not GluR1 or GluR4, were found to be significantly altered in the hippocampus of p75NTR-deficient mice. These results implicate p75NTR in activity-dependent synaptic plasticity and extend the concept of functional antagonism of the neurotrophin signaling system.     

异氟醚预处理通过上调海马 AMPA 受体GluR1亚基表达改善局灶性脑缺血再灌注损伤大鼠学习记忆功能

目的：探讨异氟醚预处理对脑缺血再灌注损伤大鼠学习记忆的影响及其可能机制。方法36只雄性成年Sprague-Daw ley大鼠,采用随机数字表法分为假手术组、缺血再灌注组和异氟醚预处理组,每组12只。采用改良线栓法制作大脑中动脉闭塞（ middle cerebral artery occlusion, MCAO）脑缺血再灌注模型。异氟醚预处理组每天吸入1.5％异氟醚1 h,连续5 d,末次预处理后24 h制作MCAO模型。 MCAO后24 h时采用2,3,5-氯化二苯四氮唑染色检测脑梗死体积;MCAO后1、3、7和14 d时进行改良神经功能缺损程度评分（modified Neurological Severity Score, mNSS ）;MCAO后9 d时采用水迷宫实验评价大鼠学习记忆;14 d时采用蛋白质印迹法检测缺血侧海马组织谷氨酸受体1（glutamate receptor 1, GluR1）蛋白表达水平。结果假手术组大鼠未见明显梗死灶,异氟醚预处理组大鼠梗死体积较脑缺血再灌注组显著缩小[（26.383±3.128）％对（19.107±1.661）％;P<0.05]。假手术组未见神经功能缺损（0分）,异氟醚预处理组MCAO 后1、3、7和14 d时mNSS评分较缺血再灌注组均显著降低[1 d：（9.000±1.195）分对（11.500±1.414）分;3 d：（6.625±1.407）分对（6.625±1.407）分;7 d：（5.875±0.707）分对（7.375±1.407）分;14 d：（3.375±1.187）分对（5.125±1.246）分;P均＜0.05]。水迷宫实验显示,异氟醚预处理组MCAO 后1~5 d时逃避潜伏期分别为（95.992±15.734） s、（70.949±14.708） s、（39.660±7.413） s、（22.692±5.778） s和（14.906±4.336）s,显著短于缺血再灌注组的（103.008±11.654）s、（94.705±14.709）s、（65.716±10.155）s、（35.240±8.553）s和（22.890±10.381）s（P均<0.05）。异氟醚预处理组穿越平台次数和目标象限停留时间百分比为（4.556±1.333）次和（33.014±5.223）％,显著多于和高于脑缺血再灌注组的（2.889±1.536）次和（21.978±6.697）％（P均＜0.01）。假手术组、脑缺血再灌注组和异氟醚预处理组缺血侧海马GluR1蛋白水平分别为0.871±0.153、0.456±0.130和0.689±0.126,3组间存在显著性差异（ F=18.329,P<0.001）,异氟醚预处理组显著高于缺血再灌注组（ P<0.05）。结论异氟醚预处理可改善脑缺血再灌注大鼠的学习记忆,其机制可能与上调海马组织G luR1表达有关。     

Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor

Phosphorylation of synaptic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) (AMPA) receptors (AMPARs) is an essential component of cerebellar long-term depression (LTD), a form of synaptic plasticity involved in motor learning. Here, we report that protein phosphatase 2A (PP-2A) plays a specific role in controlling synaptic strength and clustering of AMPARs at synapses between granule cells and Purkinje cells. In 22- to 35-day cerebellar cultures, specific inhibition of postsynaptic PP-2A by fostriecin (100 nM) or cytostatin (10-60 microM) induced a gradual and use-dependent decrease of synaptic current evoked by the stimulation of a single granule cell, without altering receptor kinetics nor passive electrical properties. By contrast, PP-2A inhibition had no effect on immature Purkinje cells (12-15 days). Concurrent PP-2A inhibition and AMPAR stimulation induced a reduction of miniature synaptic currents and a reduction of AMPAR density at synapses. Either PP-2A inhibitor alone or AMPA stimulation alone had no significant effect. Inhibition of PP-1 by inhibitor 1 (10-27 units/microl) had no effect on synaptic current. Synaptic depression induced by PP-2A inhibition occluded subsequent induction of LTD by conjunctive stimulation and was abolished by a calcium chelator or a protein kinase inhibitor, suggesting a shared molecular pathway and involvement of PP-2A in LTD induction.     

PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression

The dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses is crucial for synaptic transmission, plasticity, learning, and memory. The protein interacting with C-kinase 1 (PICK1) directly interacts with GluA2/3 subunits of the AMPARs. Although the role of PICK1 in regulating AMPAR trafficking and multiple forms of synaptic plasticity is known, the exact molecular mechanisms underlying this process remain unclear. Here, we report a unique interaction between PICK1 and all three members of the protein kinase C and casein kinase II substrate in neurons (PACSIN) family and show that they form a complex with AMPARs. Our results reveal that knockdown of the neuronal-specific protein, PACSIN1, leads to a significant reduction in AMPAR internalization following the activation of NMDA receptors in hippocampal neurons. The interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis. Similarly, the binding of PICK1 to the ubiquitously expressed PACSIN2 is also regulated by the homologous phosphorylation sites within the PACSIN2-variable region. Genetic deletion of PACSIN2, which is highly expressed in Purkinje cells, eliminates cerebellar long-term depression. This deficit can be fully rescued by overexpressing wild-type PACSIN2, but not by a PACSIN2 phosphomimetic mutant, which does not bind PICK1 efficiently. Taken together, our data demonstrate that the interaction of PICK1 and PACSIN is required for the activity-dependent internalization of AMPARs and for the expression of long-term depression in the cerebellum.     

Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence.

The Ca2+ permeability and the rectifying properties of the glutamate receptors assembled from the subunits GluR1-GluR4 depend upon a critical Arg in the GluR2 subunit located in a domain that has been proposed to span the membrane. The GluR2 subunit gene encodes a Gln (CAG) at this position, whereas the mRNA is edited so that it encodes an Arg (CGG) at this position [Sommer, B., Kohler, M., Sprengel, R. & Seeburg, P. H. (1991) Cell 67, 11-20]. The editing process is specific since only the GluR2 subunit RNA is edited even though the GluR1, GluR3, and GluR4 RNAs have a similar sequence. We show that this selective RNA editing depends upon a critical intron sequence in the GluR2 gene. This critical intron sequence is sufficient to cause editing of the GluR3 subunit exon in a chimera minigene constructed so that the GluR3 exon is placed upstream to the GluR2 intron sequence. Transfections of a neuronal cell line, N2a, with minigene constructs encoding different fragments of the GluR2 gene demonstrate that the 5' part of the 3' intron is essential for editing. Part of the exon and this critical intron sequence contains an inverted repeat that can fold into a structure consisting of three helical elements. Similar conclusions were reached by Higuchi, M., Single, F. n., Köhler, M., Sommer, B., Sprengel, R. & Seeburg, P. H. [(1993) Cell 75, 1361-1370]. These experiments demonstrate that the low Ca2+ permeability of the ionotropic non-N-methyl-D-aspartate glutamate receptors depends upon RNA editing, which requires a sequence in an intron 3' to the exon.     

Expression of Erk kinase,AMPA receptor subunits GluR1 and GluR2,and protection of chondroitin sulfate in brain of rats with chronic fluorosis

<正>Objective To study the mechanism of central nervous system (CNS) injury in chronic fluorosis and the neuroprotective effect of chondroitin sulfate (CS).Methods Forty-eight female Sprague-Dawley rats weigh-     

Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid

We report the crystal structure of the glycosylated ligand-binding (S1S2) domain of the kainate receptor subunit GluR6, in complex with the agonist domoate. The structure shows the expected overall homology with AMPA and NMDA receptor subunit structures but reveals an unexpected binding mode for the side chain of domoate, in which contact is made to the larger lobe only (lobe I). In common with the AMPA receptor subunit GluR2, the GluR6 S1S2 domain associates as a dimer, with many of the interdimer contacts being conserved. Subtle differences in these contacts provide a structural explanation for why GluR2 L483Y and GluR3 L507Y are nondesensitizing, but GluR6, which has a tyrosine at that site, is not. The structure incorporates native glycosylation, which has not previously been described for ionotropic glutamate receptors. The position of the sugars near the subunit interface rules out their direct involvement in subunit association but leaves open the possibility of indirect modulation. Finally, we observed several tetrameric assemblies that satisfy topological constraints with respect to connection to the receptor pore, and which are therefore candidates for the native quaternary structure.     

Novelty acquisition is associated with induction of hippocampal long-term depression

Homosynaptic long-term depression (LTD) consists of a persistent nonpathological decrease in synaptic transmission, which is induced by low-frequency stimulation. In vivo, low-frequency stimulation (1 Hz, 900 pulses) induces LTD in Wistar but not Hooded Lister rats. In this study, we investigated the influence of behavioral learning and behavioral state on the expression of LTD in both rat strains. Recordings were taken from freely moving animals that had undergone chronic implantation of a recording electrode in the hippocampal CA1 region and a bipolar stimulating electrode in the ipsilateral Schaffer collateral-commissural pathway. Exposure of the rat strains to stress induced a significant elevation in serum corticosterone levels but did not facilitate LTD expression. However, LFS given during exploration of a novel environment resulted in LTD expression in Hooded Lister, and LTD enhancement in Wistar, rats. Reexposure to the same environment did not result in new expression of LTD. Behavioral comparison between the first and second environmental exposure confirmed that the animals had habituated to the novel environment. These observations strongly implicate an association between novelty acquisition and LTD.     

Transsynaptic neuronal loss induced in hippocampal slice cultures by a herpes simplex virus vector expressing the GluR6 subunit of the kainate receptor.

Patients with severe temporal lobe epilepsy lose neurons within the CA3 and hilar regions of the hippocampus. Loss of CA3 and hilar neurons was also induced by transducing organotypic hippocampal slice cultures with a replication-defective herpes simplex virus (HSV) vector expressing the GluR6 kainate subtype of the glutamate receptor (HSVGluR6). In transduced fibroblasts, HSVGluR6 expressed a M(r) 115,000 protein that reacted with anti-GluR6 serum. After exposure of fibroblast to HSVGluR6, a kainate-dependent toxicity appeared in cells that were previously resistant to kainate. Microapplication of nanoliter amounts of recombinant HSV stocks into organotypic hippocampal slice cultures resulted in localized transduction and gene transfer at the site of microapplication. Microapplication of 100 HSVGluR6 virions into CA3 stratum pyramidale induced a large loss of CA3 pyramidal cells and hilar neurons, despite the small number of transduced neurons. This effect was not seen when 100 virions of HSVGluR6 were microapplied to CA1 stratum pyramidale. Tetrodotoxin or N-methyl-D-aspartate receptor antagonists inhibited the large loss of CA3 and hilar neurons, suggesting that the small cluster of HSVGluR6-transduced cells induced an N-methyl-D-aspartate-dependent transsynaptic loss of non-transduced neurons.     

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

How persistent synaptic and spine modification is achieved is essential to our understanding of developmental refinement of neural circuitry and formation of memory. Within a short period after their induction, both types of modifications can either be stabilized or reversed, but how this reversibility is controlled is largely unknown. We have shown previously that AMPA receptors (AMPARs) are delivered to perisynaptic regions after the induction of long-term potentiation (LTP) but are absent from perisynaptic regions after the full expression of LTP. Here, we report that perisynaptic AMPARs are GluR2-lacking and they translocate to synapses in a protein kinase C (PKC)-dependent manner. Once entering synapses, these AMPARs quickly switch to GluR2-containing in an activity-dependent manner. Absence of postinduction activity or blocking interactions between GluR2 and NSF, or GluR2 and GRIP/PICK1 results in LTP mediated by GluR2-lacking AMPARs. However, these synaptic GluR2-lacking AMPARs are not sufficient to allow reversibility of LTP. On the other hand, postsynaptic inhibition of PKC activity holds AMPARs at perisynaptic regions. As long as perisynaptic AMPARs are present, both LTP and spine expansion remain labile: they can be reverted to the baseline state together with removal of perisynaptic AMPARs, or they can enter a stabilized state of persistent increase together with synaptic incorporation of perisynaptic AMPARs. Thus, perisynaptic GluR2-lacking AMPARs play a critical role in controlling the reversibility of both synaptic and spine modifications.     

NR2B subunit of the NMDA glutamate receptor regulates appetite in the parabrachial nucleus

Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing agouti-related protein (AgRP) in adult mice leads to anorexia and starvation within 7 d that is caused by hyperactivity of neurons within the parabrachial nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic plasticity-based behavioral modifications, we hypothesized that modulation of the NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to the anorexia phenotype. We observed by Western blot analyses that ablation of AgRP neurons results in enhanced expression of NR2B along with a modest suppression of NR2A. Interestingly, systemic administration of LiCl in a critical time window before AgRP neuron ablation abolished the anorectic response. LiCl treatment suppressed NR2B levels in the PBN and ameliorated the local Fos induction that is associated with anorexia. This protective role of LiCl on feeding was blunted in vagotomized mice. Chronic infusion of RO25-6981, a selective NR2B inhibitor, into the PBN recapitulated the role of LiCl in maintaining feeding after AgRP neuron ablation. We suggest that the accumulation of NR2B subunits in the PBN contributes to aphagia in response to AgRP neuron ablation and may be involved in other forms of anorexia.NMDA receptors form glutamate-gated ion channels that mediate many forms of synaptic plasticity under physiological conditions and neuronal death under excitotoxic pathological conditions (1, 2). NMDA receptors are tetrameric complexes composed of two obligatory NR1 subunits and two regulatory NR2 and/or NR3 subunits. Multiple subtypes of NMDA receptors are identified with distinct pharmacological and biophysical properties that are predominantly determined by the type of NR2 subunit (NR2A to NR2D). NR2A and NR2B subunits are the most abundant subunits in the adult brain and differ in channel properties, synaptic localization, and protein interaction elements, all of which can contribute to the induction of synaptic plasticity (3). Some recent studies suggest that NMDA receptors play a major role in regulating feeding behavior and energy homeostasis. For example, antagonism of hindbrain NMDA receptors increases food intake, whereas activation of NMDA receptors in the nucleus tractus solitarius (NTS) is necessary for cholecystokinin-induced reduction of food intake (4, 5). Injection of NMDA receptor agonists into the lateral hypothalamus elicits feeding in satiated animals, whereas NMDA blockade suppresses food intake and can reduce body weight (6). Genetic inactivation of NR1 subunits specifically in agouti-related protein (AgRP) neurons results in marked loss of food intake and body fat and impaired feeding after a fast (7). These findings implicate NMDA receptor signaling within several neuronal circuits in the control of feeding and energy balance.Emerging evidence suggests that a complex neural network including GABAergic AgRP neurons in the hypothalamic arcuate nucleus plays a pivotal role in the control of appetite and energy metabolism (8–10). Activation of AgRP neurons promotes food intake and body weight gain by inhibiting postsynaptic target neurons in the paraventricular hypothalamus (10). Ablation of AgRP neurons by administration of diphtheria toxin (DT) to mice that express the diphtheria toxin receptor (DTR) selectively in AgRP neurons (Agrp^DTR mice) results in aphagia and a fatal loss of body weight caused by the hyperactivity of postsynaptic neurons in the parabrachial nucleus (PBN) as a consequence of losing inhibitory GABAergic signals (11–13). This anorexic response can be prevented by benzodiazepine potentiation of GABA signaling, by genetic blockade of NMDA glutamate receptor signaling in the PBN, or by reducing glutamatergic input or output from the PBN, including knockdown of NMDA expression in the PBN (14). However, the physiological roles of NMDA receptors in the PBN in modulating appetitive behavior have not been identified.We explored the potential benefit of pretreatment with LiCl because this salt has been shown to affect the activity of the PBN and to modulate NMDA receptor functions. Lithium is commonly used to treat bipolar mood disorder, but it also can elicit robust neuroprotection against excitotoxicity in CNS neurons (15, 16). Long-term exposure to LiCl protects cultured cerebellar, cortical, and hippocampal neurons against glutamate-induced excitotoxicity; this protection can be attributed, in part, to the inhibition of NMDA receptor-mediated calcium influx (17). Significant weight gain is associated with prolonged lithium therapy in patients with bipolar disorder; these patients have enhanced preference for a high-calorie diet, but the mechanism(s) causing this metabolic effect are unknown (18). It is well documented that a single i.p. dose of LiCl produces gastrointestinal malaise that is coincident with the induction of Fos in certain brainstem structures, including the NTS and the PBN (19, 20). Exposure of rodents to a novel taste followed by LiCl treatment produces robust conditioned aversion to that taste, and electrolytic lesions of the PBN prevent LiCl-mediated conditioned taste aversion (21). These results are consistent with the idea that LiCl activates vagal afferents to the NTS, which then relays an excitatory, glutamatergic signal to the PBN where it induces Fos in a subpopulation of PBN neurons. We hypothesized that robust glutamatergic signaling induced in the PBN by LiCl treatment might lead to synaptic plasticity involving NMDA receptors and that these changes might influence the anorexia phenotype associated with the sudden loss of GABAergic input to the PBN from AgRP neurons.     

Expression of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate (GluR2/3) receptors and N-methyl-D-aspartate receptor subtype 1 (NMDAR1) was carried out by immunohistochemistry, double immunofluorescence and real-time RT-PCR analysis in the pineal glands of 1-day to 6-wk-old rats in the present study. GluR2/3 immunopositive cells were distributed throughout the pineal gland and showed branching processes in all age groups. The NMDAR1 immunoreactivity, however, was observed in fewer branched cells. A constitutive mRNA expression of NMDAR1, GluR2 and GluR3 was detected in the pineal glands of various ages and showed no significant difference between the age groups studied. Immunohistochemical and double immunofluorescence results showed that the GluR2/3 were mainly expressed and co-localized with OX-42-positive microglia/macrophages and the glial fibrillary acidic protein (GFAP)-positive astrocytes. Co-localization of NMDAR1 with OX-42- and GFAP-positive cells was much less. The expression of these receptors on the glial cells suggests that they may be involved in the development and growth of the pineal gland in the early postnatal period (1 day to 3 wk) and subsequently in the regulation of melatonin synthesis.     

短时重复游泳调节SAM8鼠AMPA受体GluR1亚单位的磷酸化

目的观察短时重复游泳训练对SAM鼠AMPA受体GluR1亚单位磷酸化的影响,探讨运动改善脑功能的可能机制。方法选取3月龄SAMP8(prone/8)亚系为研究对象,运动模型采用2 w游泳方案:2次/d,每次6 min的游泳,结束后给予浴巾擦干放回鼠笼;对照组则在相同时间每天给予两次相同的浴巾安抚刺激。采用Western印迹方法,检测SAM8鼠海马和皮层AMPA受体GluR1亚单位Ser831和Ser 845位点的磷酸化水平的变化。结果 SAMP8海马、皮层中AMPA受体GluR1亚单位Ser831和Ser845磷酸化水平与对照组相比均增加(P<0.05)。结论 2 w的短时间重复游泳运动作为一种应激诱导剂促进了AMPA受体的活化,这可能是运动改善脑功能的机制之一。