Induction of long-term potentiation at Schaffer collateral-CA1 synapses in mice hippocampus after IMPX977 administration / 中草药·英文版

Objective: To investigate the effects of IMPX977 on long term potentiation (LTP) at Schaffer collateral-CA1 synapses in vitro and on methyl CpG binding protein 2 (Mecp2) expression in mice cortex and hippocampus. Methods: Thirty-two C57BL/6 mice were randomly divided into four groups: control, olive oil (vehicle), IMPX977 low (5 mg/kg) and high (15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting. Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced fEPSP (field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to (179.6 ± 17.8)% and (191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated MeCP2 protein level in cortex. Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.

Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function / 神经科学通报·英文版

Rho-associated kinases (ROCKs) are serine-threonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton. Two ROCK isoforms (ROCK1 and ROCK2) are expressed in the mammalian central nervous system. Although ROCK activity has been implicated in synapse formation, whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear. Here, we used a genetic approach to address this long-standing question. Both Rock1 and Rock2 mice had impaired glutamatergic transmission, reduced spine density, and fewer excitatory synapses in hippocampal CA1 pyramidal neurons. In addition, both Rock1 and Rock2 mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests. However, the spine morphology of CA1 pyramidal neurons was altered only in Rock2 but not Rock1 mice. In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time. Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.

Analysis of Differences of Antidepressant Effect of Yueju Pill between Balb/c Mice and C57BL/6J Mice / 世界科学技术-中医药现代化

This paper aimed at comparing the differences of antidepressant effects of Yueju Pill between the Balb/c mice and C57 BL/6 J mice and analyzing the effects on synaptic transmission in mice prefrontal cortex. Healthy adult Balb/c mice and C57 BL/6 J mice were randomly divided into control group and Yueju Pill group. Control group was treated with saline, Yueju Pill group was treated with single dose of Yueju Pill (13.5 g·kg-1) . The forced swimming test (FST) was measured 30 min after administration. The field excitatory postsynaptic potential (fEPSP) and long-term potentiation (LTP) of mice prefrontal cortex were detected by the electrophysiological experiment. In FST, the immobility time of Balb/c mice in Yueju Pill group was significantly lower than that in control group (P ＜ 0.01), and the immobility time of C57 BL/6 J mice showed no remarkable difference between Yueju Pill group and control group (P＞ 0.05) . In electrophysiological experiment, the percentage of slope of fEPSP in Balb/c mice in Yueju Pill group was significantly higher than that in control group (P ＜ 0.01), while there was no significantly difference in C57 BL/6 J mice between Yueju Pill group and control group (P＞ 0.05) . The LTP of Balb/c mice in Yueju Pill group was significantly increased than that in control group (P ＜ 0.01), while there was no significantly difference in LTP of C57 BL/6 J mice between Yueju Pill group and control group (P＞ 0.05) . Yueju Pill may display rapid antidepressant effect via increasing fEPSP and LTP in prefrontal cortex of Balb/c mice and then enhancing the synaptic transmission.

Research Progress in Synaptic Plasticity Impairment of Diabetic Encephalopathy / 中国药学杂志

Previous studies demonstrate that diabetes mellitus induces cognitive impairment,leading to diabetic encephalopathy(DE), which is closely related with hippocampal synaptic plasticity impairment,including synaptic structural and functional damage. Structural damage mainly embodied in the synapse degeneration.Functional damage mainly reflects in the LTP damage, including the composition variation and functional lesions of N-methyl-D-aspartate receptors(NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and patassium channels.Abnormal synaptic plasticity may be critical in the pathogenesis of diabetic encephalopathy. In this review, we summarized the relationship between DE and synaptic plasticity impairment.

Effects of Kaixin Powder on LTP in vivo and expression of PSD-95 in APP/PS1 transgenic mice / 中成药

AIM To explore the effects of Kaixin Powder (Polygalae Radix,Ginseng Radix et Rhizoma,Poria and Acori tatarinowii Rhizoma) on hippocampal long-term potentiation (LTP) in vivo in APP/PS1 transgenic mice and expression of PSD-95 in hippocampus CA1 area and cerebral cortex.METHODS Thirty-two 3-monthold male APP/PS1 mice were randomly divided into model group,Donepezil [0.75 mg/(kg · d)] group,Kaixin Powder [1.5,3 g/(kg · d)] groups.C57/BL6 mice were used as the control group.Kaixin Powder and Donepezil were administered to the APP/PS1 mice for three months,respectively.Afterwards,the LTP in vivo was recorded in a perforant pathway-dentate gyrus in the hippocampus.Immunohistochemical method was used for measuring the expression of PSD-95 in hippocampus CA1 area and cerebral cortex.RESULTS The fEPSPs slopes were significantly decreased in the model group as compared with the control group.Kaixin Powder or Donepezil treatment significantly enhanced the fEPSPs slopes in the model group.The average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex was obviously decreased in the model group.Donepezil increased the average optical density of PSD-95 positive cells in hippocampus CA1 area.Kaixin Powder [1.5 g/(kg · d)] increased the average optical density of PSD-95 positive cells in hippocampus CA1 area and cerebral cortex.Kaixin Powder [3 g/(kg · d)] increased the average optical density of PSD-95 positive cells in cerebral cortex.CONCLUSION Kaixin Powder can promote the LTP formation in APP/PS1 transgenic mice and enhance synaptic plasticity,which may be related to the regulation of protein expression of PSD-95.

Effects of Tiaoxin Formula on Spatial Learning and Memory Ability and LTP in Hippocampus of APP/PS1 Double Transgenic Mice with Alzheimer Disease / 中国中医药信息杂志

Objective To investigate the effects of Tiaoxin Formula on spatial learning and memory ability and long-term potentation (LTP) in the hippocampus of APP/PS1 transgenic mice with Alzheimer disease; To discuss its mechanism of action. Methods Totally 54 three-month-old APP/PS1 transgenic mice were randomly divided into model control group, Tiaoxin Formula group and positive control group, with 18 mice in each group. Another 18 three-month-old C57BL/6J wild mice were chosen as normal control group. All administration groups receive relevant medicine. 12 weeks later, Morris water maze test was used to test behavior and in vitro electrophysiology record. Results The Morris water maze test showed that in place navigation test, compared with the model control group, escape latency time in Tiaoxin Formula group was significantly reduced (P0.05). Conclusion Tiaoxin Formula can improve the spatial learning and memory ability and LTP of APP/PS1 transgenic mice with Alzheimer disease, thus can realize cognitive protection effects.

Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram

Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/ depression (LTP-/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses.

Unraveling the mystery of cognitive reserve.

In 1913, no less than Santiago Ramon y Cajal, pioneer of the neuron doctrine, wrote, ‘In the adult brain, nervous pathways are fixed and immutable; everything may die, nothing may be regenerated’ (Cajal 1913/1959, p 750). This stagnant view of the brain lingered in neurology for several decades, and was regularly provided as an explanation when a patient’s recovery from a stroke or brain injury was minimal or elusive. Our current understanding, however, is radically and very importantly different. The human brain – even the adult human brain – is, in fact, remarkably plastic. This enduring neuroplasticity is fundamental to the brain’s mechanisms for coping with disease and injury. As the world’s population ages, this is becoming increasingly evident. The question now emerging in the field, however, lies not in the ubiquity of agerelated disorders such as Alzheimer’s disease (AD), but in the individual variability of their onset. Alzheimer’s can now be diagnosed with reasonable consistency: several academic centres report up to 90% correlation between clinical diagnoses and autopsy diagnoses of AD (Cummings et al. 1998). However, the relationship between the severity of clinical symptoms and observable neuropathology is far from direct. This was particularly brought to light in 1989, when Katzman et al. performed postmortem analyses of the brains of 137 nursing home patients. The patients’ cognitive abilities had been monitored at the nursing home, and these records were compared with the neuropathology observed during dissection. They unexpectedly found that the brains of 10 of the subjects, who had been assessed as having unimpaired cognitive function throughout their lives, in fact displayed neuropathology that surpassed the criteria for diagnosis of AD. These individuals also happened to have heavier and more neuron-dense brains than controls, which they concluded must have afforded some ‘reserve’ that prevented the symptoms of the disease from manifesting. There are two primary theories that attempt to explain such a discrepancy. Brain reserve (BR) refers to tangible individual differences such as brain size and dendritic density, as was noticed by Katzman et al. (1989), BR is considered a passive ‘threshold’ model of reserve: once a certain threshold for brain damage is exceeded, symptoms of cognitive decline begin to manifest. Cognitive reserve (CR), on the other hand, is considered an active model: the brain attempts to compensate for cognitive damage by implementing alternate mechanisms in place of the damaged networks. A brain that has engaged in activities that enhance this cognitive flexibility is therefore better equipped to cope with damage than one that has not (Stern, 2002). Barulli and Stern (2013) argue that these theories are complementary rather than competing. Like any complex human trait, resilience against brain damage appears to be constructed of a cocktail of genetics, environment and experience. The greater the resolution with which brain structures can be visualized and molecular pathways leading to plasticity are understood, the more the two theories are liable to overlap. Nevertheless, it remains that the environmental component can be manipulated to favour reserve. As a result, much of the current literature concerning reserve focuses on identifying lifestyle factors that may improve CR. Higher level of education, occupational complexity and physical and intellectual leisure activities have all been found to consistently correlate with increased CR (Verghese et al. 2003; Potter et al. 2008; Valenzuela and Sachdev 2009). Recently, bilingualism as a CR-improving factor has received much attention. The original studies in this area found a highly significant effect of lifelong bilingualism on the onset of AD, and are textbook examples of CR in effect. The first, by Craik, Bialystok and Freedman (2010), retrospectively analysed the medical records of 211 elderly Canadians diagnosed with AD. The records contained detailed language histories, based on which 102 were classified as bilingual and 109 as monolingual. On comparison, the bilingual group showed an onset of AD symptoms on average 5.1 years

Factors associated with conversion of long-term non-progressors to progressors: A prospective study of HIV perinatally infected paediatric survivors.

Background & objectives: Survival pattern among children infected with the human immune deficiency virus (HIV) follows a bimodel distribution. Some children survive beyond 9 years age and are known as long term survivers (LTS) while others had a more rapid course to death during the first few years of life. In the LTS group of children, two sub-populations have emerged, the long term non-progressors (LTNP) who have remained asymptomatic over a period of years and those who have survived despite clinical and laboratory evidence of disease progression, the long term progressors (LTP). The aim of the present study was to determine the factors influencing the conversion of LTNPs to LTPs in a group of perinatally HIV infected children who were followed up for five years. Methods: A total of 26 HIV seropositive paediatric patients were monitored from 2006 to 2011 with CD4 cell counts, onset of clinical manifestations, body weight, biochemical, haematological and immunological parameters. Statistical analyses, both qualitative and quantitative, were used to determine the degree of conversion of non-progressors to progressors. Results: All 26 (13 female and 13 male) perinatally HIV infected children, born during1991-1996 were healthy until 2006. But by 2011, 18 were placed in progressors group with antiretroviral therapy (ART), while six remained in non progressors group and two died. As per the Kaplan-Meier survival analysis, AIDS free median survival period (years) in LTP group (CD4 count) of the cohort was 10±0.66 (<200; P=<0.05); 11±0.61 (200-350, P=<0.05), 12±0.18 (>350, P=<0.05). Intercurrent and opportunistic infections (OIs) were observed in LTPs only. The incidence of OI in LTPs was higher when compared to general paediatric population. Interpretation & conclusions: Our findings show that CD4 counts and OIs play an important role in influencing the survival chances of perinatally HIV infected children.

Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase Cdelta and epsilon

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration-dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 (10microM); the selective PKCdelta inhibitor, rottlerin (1microM); and the PKCepsilon inhibitor, TAT-epsilonV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50microM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCdelta and/or PKCepsilon, and confirm that NMDAR activity is required for this effect.

A Functional Role for CREB as a Positive Regulator of Memory Formation and LTP

cAMP response element-binding protein (CREB), a transcription factor, has been shown to play a central role in memory formation, and its involvement in this process has been investigated using a wide range of animal models, from nematodes to higher animals. Various CREB mutant mice have been developed and investigated. Several types of mutant mice with loss of CREB function have impaired memory formation and long-term potentiation (LTP), suggesting that CREB plays essential roles in these processes. To characterize the roles of CREB in memory formation and LTP further, mutant mice displaying gain of CREB function have been generated and analyzed. Importantly, CREB-DIEDML mice and CREB-Y134F mice showed enhanced memory formation, whereas CREB-VP16 mice displayed a lowered threshold of long-lasting LTP (L-LTP) induction, strongly suggesting that CREB functions as a positive regulator of memory formation and LTP. In this review, I focus on the effects of the genetic activation of CREB in LTP and memory formation and summarize previous findings.

Long-term potentiation and long-term depression: a clinical perspective

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Effect of Electroacupuncture on Hippocampal LTP in Alzheimer's Disease Rats Induced by A?_(25-35) / 针刺研究

Objective To observe the effect of electroacupuncture(EA) on the learning-memory ability in Alzheimer's disease(AD) rats.Methods Thirty SD rats were equally randomized into control,model and EA groups.AD model was established by injecting ?-amyloid(A?25-35,10?g) into the bilateral dentate gyri of the hippocampal CA 1 area(AP-3.5mm,ML?2.0mm,DV 2.7mm).EA(4Hz,1-2mA) was applied to "Baihui"(GV 20),"Dazhui"(GV 14),bilateral "Shenshu"(BL 23) and bilateral "Yongquan"(KI 1) for 30min,once daily for 7 days.The learning-memory ability was detected by using step-down test.Long term potentiation(LTP) of hippocampal CA 1 area was recorded by using tungsten microelectrodes after high frequency stimulation(HFS) conditioning of the cortical anterior perforated substance.Results In AD rats,the error number and total error time of step-down test were increased significantly(P

NR2B receptor antagonist Ro25-6981 inhibits newborn neuron induced long-term potentiation in the dentate gyrus of adult rats / 中国组织工程研究

BACKGROUND: Newborn neurons have bean shown to induce long-term potentiation (LTP). Activation of N-methyl-D-aspartic acid (NMDA) receptor subunit NR2B plays an important role in mature neurons-induced LTP. But there have been no reports addressing on the effects of NR2B activation on newborn neuron-induced LTP.OBJECTIVE: To investigate the effects of NR2B receptor antagonist Ro25-6981 on LTP induced by newborn neurons in adult rat dentate gyrus.DESIGN, TIME AND SETTING: An electrophysiological recording trial was performed at the Department of Neuroblology,Shanxi Medical University from February to June 2007.MATERIALS: Twenty-six male Wistar rats, aged 3 months, were provided by Laboratory Animal Center, Shanxi Medical University.METHODS: Following sacrifice for brain harvesting under anesthesia, the hippocempus was taken to preparation of 400 μ mol/L brain slices. Using extracellular field potential recordings, low-frequency stimulation was performed in the medial molecular layer of dentate gyrus with insulated bipolar tungsten electrodes. After having stable recordings, LTP was induced under high-frequency tetanic stimulation. LTP was induced with a protocol developed previously (4 trains, 500 ms each, 100 Hz within the train, repeated every 20 s). Only those slices which produced the field excitatory postsynaptic potential of 1 mV or cerebrospinal fluid (ACSF)-induced LTP (ACSF-LTP): brain slices were divided into 2 groups: ACSF group, in which, slices were continuously perfused using ACSF bubbled with 95% O2 and 5% CO2; ACSF+ Ro25-6981 group: a 10-minute treatment with 3μ mol/L Ro25-6981 was performed prior to tetanic stimulation, and the remaining procedures were the same as ACSF divided into 2 groups: BIC group: a 10-minute treatment with 10 μmol/L BIC was performed prior to titanic stimulation; BIC+Ro25-6981 group: 3μ mol/L Ro25-6981 and 10μ mol/L BIC were simultaneously perfused 10 minutes prior to tetanic stimulation.MAIN OUTCOME MEASURES: LTP recording results.minutes of titanic stimulation, LTP was (164.67±2.40)% and (147.56±6.63)% in the BIC and BIC+ Ro25-6981 groups,respectively, and a significant difference existed between the two groups (P ＜ 0.05).

Effects of Glutamate Transporters on Synaptic Plasticity in Status Epilepticus Rats / 生物化学与生物物理进展

The effects of glutamate transporters on synaptic plasticity in rat models of pilocarpine-induced status epilepticus were investigated. Male Wista rats ((304.06?13.79) g) were randomly divided into 5 groups, short-term seizures (SE) and its control (SC), long-term seizures (LE) and its control(LC), normal control (Sham) groups. Epilepsy rat models were induced by injection of pilocarpine(25 mg/kg, i.d.). Glutamate transporter inhibitor, DL-threo-benzyloxyaspartate (TBOA, 7.5 nmol,1 ?l) was microinjected into right side of hippocampus after 14 days of initial status epilepticus in SE and LE groups. The same volumes of artificial cerebrospinal fluid were injected into same side of hippocampus in SC and LC groups. Electroencephalographys (EEG) were detected in SE and SC groups after 2 h of drug injection. Long term potential (LTP) at perforant pathway and dentate gyrus(PP-DG) and EEG were recorded in LE and LC groups after two weeks of drug injection. Example of Fluoro-Jade-B staining in the rat brain was made at the end of electrophysiological experiment. The results showed that there was a significant decrease in theta band power of EEG in SE group compared with that of SC group (P 0.05). The slope of excitatory postsynaptic potential (EPSP) was significantly increased in LE group compared with that of LC group (P

Role of retrograde messenger NO in long-term potentiation / 基础医学与临床

As an important messenger molecule, NO exists in both peripheral and central nervous system (CNS). Recently, NO was proved to play a critical role in CNS, especially in synaptic plasticity. As a kind of retrograde messenger, it plays some roles in the induction and maintenance of LTP through activation of downstream pathway or molecules, such as NO-cGMP-PKG, ADPRT and C-FOS.

Role of Src kinase in the induction and maintenance of spinal long-term potentiation / 西安交通大学学报(医学版)

Objective To evaluate the role of Src kinase in the induction and maintenance of spinal long-term potentiation(LTP).Methods The C-fiber evoked field potentials were recorded at the superficial layers of spinal dorsal horn at the lumbar enlargement.Results ① Genistein(200?mol/L) or PP2(100?mol/L),a selective Src kinase inhibitor,completely blocked LTP induction when administered at 30min prior to tetanic stimulation.② Genistein or PP2 reversed spinal LTP in a time-dependent manner.At 15min after LTP induction,Genistein(200?mol/L) or PP2(100?mol/L) reversed LTP completely.At 30min after LTP induction,however,the same concentration of Genistein or PP2 did not affect the spinal LTP.Conclusion Activation of Src kinase in spinal dorsal horn may be crucial for the induction and early-phase maintenance of LTP of C-fiber evoked field potentials.

The electrophysiological properties of visual cortical neurons in binocular form-depri-vated rats / 第三军医大学学报

Objective To investigate the electrophysiological properties of neurons in visual cortex of binocular form-deprivated rats during the developmental stages and to explore the synaptic and cellular mechanisms of plasticity in the visual cortex. Methods Whole cell patch clamp technique was applied to the visual cortex slices prepared from 61 Wistar rats of both genders, which were divided into two groups; control group and binocular form-deprivation (BFD) group. Excitatory postsynaptic currents (EPSCs) and long term potentiation (LTP) of the neurons were recorded. Results (1) The percentage of silent response in BFD group was significantly higher than that in the control group(P

MAPK cascade signaling and long-term potentiation / 中国药理学通报

Long-term potentiation(LTP) of synaptic activity in the hippocampal is the most widely researched model of synaptic plasticity,which is believed to underlie the brain function of learning and memory.Mitogen-activated protein kinases(MAPK) respond to a variety of cellular and extracellular stimuli, such as growth factors,cytokines,extracellular mitogen and stresses.MAPK are involved in complex processes such as in cell differentiation,proliferation and programmed cell death.It has been reported that the upstream regulators and downstream substrats of MAPKs still widely exist in the mature neuron.MAPKs cascade induces phosphorylation of many functional protein including some receptors and kinases that is associated with induction and maintain of the LTP in the neuron,indicating that MAPKs do play a crucial role in the synaptic plasticity.Extracellular signal-regulated kinase(ERK),c-Jun N-terminal kinase(JNK) and p38 activity and its relationship with LTP are reviewed.

TYROSINE PROTEIN KINASE-DEPENDENT LONG-TERM POTENTIATION IN RAT BASOLATERAL AMYGDALA / 解剖学报

Objective To compare the effects of different intervals of theta burst stimulation(TBS) on the expression of long-term potentiation(LTP) and to explore whether LTP is tyrosine protein kinase(TPK)-dependent.in basolateral amygdala(BLA).Methods Basolateral amygdala slices of rats were prepared.Field excitatory post-synaptic potentials(field potential,fEPSPs) of BLA were recorded by stimulating the external capsule.Two TBS's were applied to induce LTP in BLA.Each TBS included a brief,high-frequency pulse train(5 pulses at 100 Hz) given at the theta-rhythm(5Hz) for 4 seconds.Experiments compare the effects of different intervals of two TBS's on the expression of LTP in BLA.The role of tyrosine protein kinase(TPK) on LTP was then determined using bath application of TPK inhibitor genistein.Results Two TBS's of 10 seconds interval failed to induce LTP in BLA.However,two TBS's increased to 10 min and 30 min intervals,individually,both types of stimulations enhanced f-EPSPs.The enhanced f-EPSPs lasted for more than 30 min.LTP induced by two TBS's of 10 min and 30 min interval were blocked by the TPK inhibitor genistein.Conclusion Two TBS's of 10 min intervals was better at the induction of LTP in BLA.The activation of TPK was possibly involved in the induction and maintenance of LTP in the amygdala.