酪氨酸蛋白激酶依赖性大鼠基底外侧杏仁核的长时程增强

目的 比较不同时间间隔的两串θ频率波刺激在大鼠离体脑片基底外侧杏仁核(BLA)长时程增强(LTP)形成中的作用,并探讨BLA的LTP是否为酪氨酸蛋白激酶(TPK)依赖性.方法 制备杏仁核脑片,刺激外囊记录BLA场电位,应用两串θ频率波刺激诱导LTP,每串θ频率波刺激为20个(频率5Hz)短时间高频串脉冲(5个脉冲,频率为100Hz),通过改变两串θ频率波的刺激间隔,分析不同参数诱导的LTP是否存在差异,并在灌流的人工脑脊液中加入TPK抑制剂genistein,观察其对杏仁核I胛的影响.结果 间隔10s的两串θ频率波未能在BLA诱导出LTP;增大串刺激间隔为10min或30min,均可观察到记录的场电位(f-EPSPs)明显增大,增强的场电位持续时间超过30min,串间隔为10min的参数诱导的LTP最明显;两串θ频率波刺激诱导的LTP可被TPK抑制剂genistein所阻断.结论 串间隔为10min的两串θ频率波刺激(TBS)是BLA诱导LTP的较好参数;杏仁核的LTP可能涉及TPK的激活.     

5-羟色胺诱导冠状动脉收缩的机制研究

目的:探讨5-羟色胺(5-HT)诱导冠状动脉收缩的机制。方法:取雄性Wistar成年大鼠,制备离体冠状动脉环,经血管张力测定仪测定动脉环的张力变化,并探讨给予不同信号通路抑制剂对5-HT诱导的冠状动脉收缩的影响。结果:首先发现给予5-HT_(2A)受体阻断剂沙格雷酯(sarpogrelate,1μmol/L)可完全消除5-HT引起的冠状动脉浓度依赖性收缩;磷脂酶C_β(PLC_β)抑制剂U73122(10μmol/L和50μmol/L)、Rho相关蛋白激酶抑制剂Y-27632(3μmol/L和10μmol/L)和蛋白激酶Cδ亚基(PKCδ)抑制剂rottlerin(3μmol/L和10μmol/L)孵育后,均可明显抑制5-HT引起的冠状动脉环收缩(P0.05);此外,L-型钙通道(Cav1.2)阻断剂硝苯地平(1μmol/L)及细胞内钙池操纵性钙内流(SOCE)抑制剂SKF96365(10μmol/L和30μmol/L)和2-氨基乙氧基苯硼酸(2-APB,50μmol/L和100μmol/L)孵育后,5-HT诱导的血管收缩张力较未处理组明显下降(P0.05);另外,在含硝苯地平(1μmol/L)的无钙Kerbs-Henseleit(K-H)液中,发现5-HT仍可诱导血管收缩。结论:5-HT通过激活5-HT_(2A)受体诱导冠状动脉收缩,其机制可能与PKC和Rho激酶信号通路,以及钙调控有关。     

突触后突触结合蛋白在长时程增强过程中介导AMPA受体的胞吐作用

<正>N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体依赖性长时程增强(long-term potentiation,LTP)引起的突触联系增强具有重塑神经环路及调节学习和记忆的作用。在NMDA受体依赖性LTP诱导过程中,Ca2+内流会刺激突触α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid,AMPA)受体的募集,从而强化突触联系。然而,Ca2+诱导AMPK受体募集的机制尚未明确。Wu等的研究发现,在小鼠海马CA1区的锥体神经元中同时阻断突触结合蛋     

小鼠脊髓背角Ⅰ层-PAG投射神经元短时程突触可塑性的特征研究

目的:研究小鼠脊髓背角Ⅰ层向中脑导水管周围灰质(periaquaductal gray,PAG)投射神经元在双脉冲刺激下表现出来的短时程突触可塑性的特点。方法:选取18~21 d C57/Bl6小鼠,脑立体定位注射2.5%Di I(100 nl)至PAG,2~3 d后制备400~650μm带背根的脊髓薄片,孵育1 h后用全细胞膜片钳技术记录Di Ⅰ阳性标记的脊髓背角Ⅰ层向PAG投射(spino-PAG)神经元,在判断其为单突触传递后,给予时间间隔为110 ms的双脉冲刺激诱致刺激外周C纤维诱发的C-e EPSCs,观察其短时程突触可塑性的特点。结果:(1)应用脑立体定位注射技术向PAG注射荧光素Di Ⅰ后可在脊髓背角Ⅰ层检测到逆行标记的神经元,提示该神经元为向PAG投射的神经元(spino-PAG投射神经元)。(2)在给予脊神经背根时间间隔为110 ms的双脉冲刺激后,脊髓背角Ⅰ层spino-PAG投射神经元发生不同程度和性质的短时程突触可塑性改变。其中,52.8%(28/53)的神经元表现为短时程的双脉冲易化(paired-pulse facilitation,PPF),其PPR的平均值为1.76±0.18;47.2%(25/53)的神经元表现为短时程的双脉冲抑制(paired-pulse depression,PPD),其PPR的平均值为0.61±0.05。结论:双脉冲刺激脊神经背根诱致C-e EPSCs可使脊髓背角I层spino-PAG神经元呈现短时程易化和短时程抑制的突触可塑性特征,提示这种短时程突触可塑性可能在痛信息的传递和敏化过程中发挥重要作用。     

去除感觉神经元胞体促进离体培养的海兔感觉神经突触形成

目的 研究去除离体培养的海兔感觉神经元（SN）与运动神经元（MN,L7）互相接触形成的突触终末数量的变化。方法 体外培养无脊椎海生动物海兔（Aplysia）SN和MN,L7,两者互相接触形成突触联系fSN／L7）,培养到第4d时,将部分感觉神经细胞的体部去除（SN／L7,-CB）,其中一部分应用5-HT处理,另一部分应用5-HT＋茴香霉素（Anisomysin）处理,将仍保留细胞体部（SN／L7,＋CB）的离体培养突触作为对照组,24h后。利用免疫组织化学方法观察突触终末数目的变化。结果与对照组相比,应用5-HT后24h,5-HT处理组突触终末的数目显著增加（P〈0．01）;而5-HT＋茴香霉素组的突触终末数目却没有明显改变。结论 在长时程易化条件下,去除感觉神经细胞体可能使突触终末的数量增加,而这种感觉神经突触可塑性的变化可以被蛋白质合成抑制剂茴香霉素所抵消。     

5-HT1A受体参与腹外侧眶皮层内5-HT诱发的抗伤害效应

为了明确5-HT参与腹外侧眶皮层(VLO)的抗伤害效应以及VLO内的5-HT1A受体与该效应之间的关系,本研究采用浅麻大鼠,以甩尾反射潜伏期(TFL)为指标,观察VLO内微量注射5-HT和选择性5-HT1A受体拮抗剂p-MPPI对TFL的影响。结果显示:VLO内微量注射5-HT(2.0、5.0、10.0μg)可剂量依赖性抑制辐射热诱发的TFL;而VLO内预先5min微量注射5-HT1A受体拮抗剂p-MPPI(0.2μg)可拮抗5-HT(10.0μg)诱发的抗伤害效应。本研究的结果提示5-HT参与VLO内的抗伤害效应,而该效应可能由5-HT1A受体介导。     

催产素抑制外周刺激诱发的大鼠海马LTP及Fos蛋白表达

 目的 探讨催产素对外周刺激诱发的大鼠海马LTP及Fos蛋白表达的影响。方法 单刺激诱发海马CA1区场电位；强直刺激坐骨神经，诱发海马CA1区长时程增强场电位（LTP）。在强直刺激前于侧脑室内微量注入催产素(Oxytocin，OT)及催产素受体拮抗剂－Atosiban，观察其对LTP的影响。用免疫组化法检测海马Fos蛋白表达。结果 单刺激坐骨神经在海马CA1区诱发出潜伏期固定(171.9±33.1) ms且可重复出现的以正波为主的场电位，平均幅度(25.7±8.4) μV。强直刺激诱导LTP产生，催产素可抑制海马LTP的诱导，但预先注射Atosiban后，海马CA1区仍能出现LTP，但持续时间比对照组短。强直刺激前，海马内c-fos表达为阴性；强直刺激后，表达增强，催产素组表达则较弱，催产素加拮抗剂组也呈强阳性表达。结论 催产素抑制海马LTP的诱导，减弱c-fos的表达，而Atosiban对该效应有一定的抑制作用。提示催产素可能是通过其受体发挥作用的。     

吗啡依赖戒断焦虑大鼠杏仁核突触结构的可塑性

目的通过对吗啡依赖戒断焦虑模型大鼠杏仁核突触形态结构可塑性的观察,探讨其焦虑情绪发生的机制。方法采用剂量递增法建立大鼠吗啡依赖戒断后焦虑模型。取脑杏仁核进行突触的透射电镜观察和体视学定量分析。结果焦虑模型组大鼠杏仁核可见突触密集、数量多,但体积明显减小。与对照组比较,焦虑模型组大鼠杏仁核突触数密度、面密度均显著增高(P<0.01),突触连接带平均面积减小(P<0.05);而与丁螺环酮组比较,焦虑模型组大鼠杏仁核突触数密度、面密度也显著增高(P<0.01),而突触连接带平均面积减小(P<0.05)。结论杏仁核突触形态结构的可塑性变化可能参与了吗啡依赖戒断后焦虑情绪的发生。     

选择性5-羟色胺重摄取抑制剂的不良反应

选择性5-羟色胺重摄取抑制剂(selective se-rotonin reuptake inhibitors,SSRIs)是临床应用较广的新一代抗抑郁剂，通过选择性阻止突触间隙5-HT的重摄取，增加突触间隙5-HT的有效浓度而发挥抗抑郁作用。目前临床上常用的SSRI有5种，它们为氟西汀(fluoxetine，商品名为百忧解Pro     

去除感觉神经细胞体对突触长时程易化效应的影响

目的去除感觉神经细胞的体部,研究离体培养突触长时程易化效应的变化。方法体外培养多组由无脊椎海生动物海兔(Ap lysia)的感觉神经元(SN)和运动神经元(L7,MN)互相接触而形成的突触模型,培养到第4 d时,将部分感觉神经细胞体去除(SN/L7,-CB),其余仍保留细胞体部(SN/L7,+CB),应用5-HT处理上述突触模型,之后将处理后的模型继续培养,在此后24 h和48 h,分别检测去除和保留感觉神经细胞体突触模型的长时程易化(LTF)效应。结果在应用5-HT后24 h,去除胞体组突触的LTF明显高于保留胞体组;而在应用5-HT后48 h,去除细胞体组突触的LTF呈明显下降,与保留细胞体组无明显差异;应用5-HT后24 h和48 h保留感觉神经细胞体组突触的LTF水平无明显变化。结论去除感觉神经细胞体在较短的时程内(24 h)可以提高突触LTF表达水平,而这种高水平的LTF无法长时间维持(48 h),保留感觉神经细胞体突触的LTF在一定时程内(48 h)可以在一定水平上稳定表达。     

Serotonin type II receptor activation facilitates synaptic plasticity via N-methyl-D-aspartate-mediated mechanism in the rat basolateral amygdala

The modulation of synaptic plasticity by serotonin type II (5-hydroxytryptamine type II (5-HT(2)))-receptor stimulation was explored using intracellular, field potential and Fura-2 fluorescence image recordings in a rat amygdala slice preparation. Bath application of 5HT(2) receptor agonist 1-(2,5)-dimethoxy-4-iodophen-2-aminopropane (DOI) transformed theta-burst-stimulated (TBS) synaptic plasticity from short-term potentiation to long-term potentiation. DOI enhanced N-methyl-D-aspartate (NMDA) receptor-mediated potentials and calcium influx without affecting the resting membrane potential or input resistance of the neurons. In contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor-mediated excitatory synaptic responses were unaffected by DOI. The facilitating effects of DOI were blocked by the 5-HT(2) receptor antagonist, ketanserin, and by the 5-HT(2C)-receptor selective antagonist, RS102221. These results indicate that 5-HT(2)-receptor activation enhances NMDA receptor-mediated synaptic function in the basolateral amygdala (BLA).     

Histaminergic modulation of excitatory synaptic transmission in the rat basolateral amygdala

The effects of histamine on excitatory synaptic transmission between the external capsule and basolateral amygdala (BLA) were examined using intracellular and field potential recordings in rat amygdala slices. Bath application of histamine (20 microM) suppressed intracellular excitatory postsynaptic potentials (EPSPs; 70.3+/-5.1% of control amplitude) in 43 of 64 BLA neurons, and potentiated EPSPs (341+/-81% of control amplitude) in 21 neurons, without changing resting membrane potential or input resistance. The histamine-induced suppression of EPSPs was accompanied by an increase in paired-pulse facilitation of the slopes of EPSPs, suggesting a presynaptic locus of the action. The suppressive effect could be blocked by the selective H3 antagonist thioperamide, and mimicked by the selective H3 agonist R-alpha-methylhistamine, indicating that the suppressive effect is mediated by the presynaptic H3 receptor. The potentiating effect of histamine on EPSPs was not accompanied by the change of paired-pulse facilitation and was not affected by the presence of H1, H2 or H3 receptor antagonists. In addition, the effective concentration of agonist to produce 50% of maximal response (EC50) of the potentiating action of histamine is 49 nM, much lower than the EC50 (470 nM) of the H3 receptor-mediated suppressive effect characterized here. These observations suggest a novel, high affinity and postsynaptically mediated effect of histamine. In extracellular recordings, histamine, at low concentration (200 nM), consistently potentiated field potentials. At high concentration (20 microM), histamine suppressed field potentials, but potentiated field potentials when H3 receptors were blocked. Taken together, these results revealed that histamine, via the presynaptic H3 receptor and a currently unknown mechanism, decreases or increases excitatory synaptic transmission in the BLA respectively. This specific histaminergic modulation of neuronal activity in the amygdala may play an important role in amygdala-mediated physiological and pathophysiological processes, such as fear, emotional learning and memory, temporal lobe epilepsy, and affective disorders.     

Phasic voluntary movements reverse the aftereffects of subsequent theta-burst stimulation in humans

Theta-burst stimulation (TBS) is a technique that elicits long-lasting changes in the excitability of human primary motor cortex (M1). Tonic contraction of the target muscle modifies the aftereffects of TBS, whereas interactions between phasic muscle contraction and the aftereffects of TBS are unknown. In this paper, we investigated whether phasic voluntary movements influence TBS-induced changes in M1 excitability. We examined whether a brief sequence of phasic finger movements performed by healthy humans before both intermittent TBS (iTBS) and continuous TBS (cTBS) influences TBS-induced aftereffects. Ten healthy subjects underwent iTBS and cTBS. To evaluate the TBS-induced aftereffects on M1 excitability, single TMS pulses were given over the FDI motor area before (T0) and 5 (T1), 15 (T2), and 30 min (T3) after TBS. To find out whether finger movements influenced the TBS-induced aftereffects, we tested motor-evoked potentials (MEPs) size by single TMS pulses at T0, immediately after movements, and at T1–T3. We also measured the kinematic variables mean amplitude and mean peak velocity of the movements. When no phasic voluntary movements preceded TBS, iTBS elicited facilitatory and cTBS elicited inhibitory aftereffects on MEP size. Conversely, movements performed before TBS elicited significant changes in the direction of the TBS-induced aftereffects. iTBS produced inhibitory instead of facilitatory aftereffects and cTBS produced facilitatory instead of inhibitory aftereffects. Finger movements alone had no effects on MEPs size tested with single-pulse TMS. Peripheral electrical stimulation had no effect on iTBS-induced aftereffects. Repeated phasic finger movements interfere with TBS-induced aftereffects probably by modulating mechanisms of brain metaplasticity.     

GABAB Receptor- and Metabotropic Glutamate Receptor-Dependent Cooperative Long-Term Potentiation of Rat Hippocampal GABAA Synaptic Transmission

Repetitive stimulation of Schaffer collaterals induces activity-dependent changes in the strength of polysynaptic inhibitory postsynaptic potentials (IPSPs) in hippocampal CA1 pyramidal neurons that are dependent on stimulation parameters. In the present study, we investigated the effects of two stimulation patterns, theta-burst stimulation (TBS) and 100 Hz tetani, on pharmacologically isolated monosynaptic GABAergic responses in adult CA1 pyramidal cells. Tetanization with 100 Hz trains transiently depressed both early and late IPSPs, whereas TBS induced long-term potentiation (LTP) of early IPSPs that lasted at least 30 min. Mechanisms mediating this TBS-induced potentiation were examined using whole-cell recordings. The paired-pulse ratio of monosynaptic inhibitory postsynaptic currents (IPSCs) was not affected during LTP, suggesting that presynaptic changes in GABA release are not involved in the potentiation. Bath application of the GABA_B receptor antagonist CGP55845 or the group I/II metabotropic glutamate receptor antagonist E4-CPG inhibited IPSC potentiation. Preventing postsynaptic G-protein activation or Ca²⁺ rise by postsynaptic injection of GDP-β-S or BAPTA, respectively, abolished LTP, indicating a G-protein- and Ca²⁺-dependent induction in this LTP. Finally during paired-recordings, activation of individual interneurons by intracellular TBS elicited solely short-term increases in average unitary IPSCs in pyramidal cells. These results indicate that a stimulation paradigm mimicking the endogenous theta rhythm activates cooperative postsynaptic mechanisms dependent on GABA_BR, mGluR, G-proteins and intracellular Ca²⁺, which lead to a sustained potentiation of GABA_A synaptic transmission in pyramidal cells. GABAergic synapses may therefore contribute to functional synaptic plasticity in adult hippocampus.     

Serotonergic modulation of neurotransmission in the rat basolateral amygdala.

Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Synaptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 +/- 38 pA in amplitude, lasted 296 +/- 27 mS, and were blocked by the GABAA receptor antagonist, bicuculline methiodide (30 microM). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 +/- 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive, high-amplitude (260 +/- 42 pA), long-duration (139 +/- 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 +/- 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 +/- 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent, membrane depolarization mediated by a 45 +/- 6.9 pA inward current, which had a reversal potential of -90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), but not by the 5-HT1A receptor agonist, (+/-) 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-HT evoked an indirect membrane hyperpolarization ( approximately 2 mV) that was associated with a 75 +/- 42 pA outward current and had a reversal potential of -70 mV. The response was independent of 5-HT concentration, blocked by TTX, mimicked by alpha-methyl-5-HT but not by 8-OH-DPAT. In interneurons, 5-HT reduced the amplitude of the evoked EPSC and in the presence of TTX (0.6 microM) reduced the frequency of miniature EPSCs but not their quantal content. In projection neurons, 5-HT also caused a dose-dependent reduction in the amplitude of stimulus evoked EPSCs and IPSCs. These results suggest that acute serotonin release would directly activate GABAergic interneurons of the BLA, via an activation of 5-HT2 receptors, and increase the frequency of inhibitory synaptic events in projection neurons. Chronic serotonin release, or high levels of serotonin, would reduce the excitatory drive onto interneurons and may act as a feedback mechanism to prevent excess inhibition within the nucleus.     

Aging effects on the limits and stability of long-term synaptic potentiation and depression in rat hippocampal area CA1

Altered hippocampal synaptic plasticity may underlie age-related memory impairment. In acute hippocampal slices from aged (22-24 mo) and young adult (1-12 mo) male Brown Norway rats, extracellular excitatory postsynaptic field potentials were recorded in CA1 stratum radiatum evoked by Schaffer collateral stimulation. We used enhanced Ca(2+) to Mg(2+) ratio and paired-pulse stimulation protocol to induce maximum changes in the synaptic plasticity. Six episodes of theta-burst stimulation (TBS) or nine episodes of paired low-frequency stimulation (pLFS) were used to generate asymptotic long-term potentiation (LTP) and long-term depression (LTD), respectively. In addition, long-term depotentiation (LTdeP) or de-depression (LTdeD) from maximal LTP and LTD were examined using two episodes of pLFS or TBS. Multiple episodes of TBS or pLFS produced significant LTP or LTD in aged and young adult rats; this was not different between age groups. Moreover, there was no significant difference in the amount of LTdeP or LTdeD between aged and young adult rats. Our results show no age differences in the asymptotic magnitude of LTP or LTD, rate of synaptic modifications, development rates, reversal, or decay after postconditioning. Thus impairment of the basic synaptic mechanisms responsible for expression of these forms of plasticity is not likely to account for decline in memory function within this age range.     

Inhibitory transmission in the basolateral amygdala.

1. Intracellular recording techniques were used to characterize synaptic inhibitory postsynaptic potentials (IPSPs) recorded from neurons of the basolateral nucleus of the amygdala (BLA). Bipolar electrodes positioned in the stria terminalis (ST) or lateral amygdala (LA) were used to evoke synaptic responses at a frequency of 0.25 Hz. 2. Two synaptic waveforms having IPSP components could be evoked by electrical stimulation of either pathway: a biphasic, excitatory postsynaptic potential (EPSP), fast-IPSP (f-IPSP) waveform, and a multiphasic, EPSP, f-IPSP, and subsequent slow-IPSP (s-IPSP) waveform. Expression of either waveform was dependent on the site of stimulation. ST stimulation evoked a similar number of biphasic (45%) and multiphasic (50%) synaptic responses. In contrast, stimulation of the LA pathway evoked mainly (80%) multiphasic synaptic responses. 3. Both the f- and s-IPSP elicited by ST stimulation could be reduced in amplitude in the presence of the glutamatergic, N-methyl-D-aspartate (NMDA) antagonist, (DL)-2-amino-5-phosphonovaleric acid (APV, 50 microM), and were abolished by the glutamatergic, non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). In contrast, a CNQX-resistant f-IPSP was evoked with LA stimulation and abolished by subsequent addition of bicuculline methiodide (BMI), a gamma-aminobutyric acid (GABAA) receptor antagonist, suggesting direct inhibition of BLA neurons by GABAergic LA interneurons. The sensitivity of the s-IPSPs and the f-IPSPs to glutamatergic antagonists suggests the presence of feed-forward inhibition onto BLA neurons. 4. The f-IPSP possessed characteristics of potentials mediated by GABAA receptors linked to Cl- channels, namely, a reversal potential of -70 mV, a decrease in membrane resistance (13.5 M omega) recorded at -60 mV, a block by BMI, and potentiation by sodium pentobarbital (NaPB). 5. The s-IPSP was associated with a resistance decrease of 4.5 M omega, a reversal potential of -95 mV, and was reversibly depressed (approximately 66%) by 2-hydroxy-saclofen (100 microM), suggesting activation of GABAB receptors. 6. The large resistance change associated with the f-IPSP, its temporal overlap with evoked EPSPs, and the development of both spontaneous and evoked burst firing in the presence of BMI suggests that the f-IPSP determines the primary state of excitability in BLA neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modulation of late phases of long-term potentiation in rat dentate gyrus by stimulation of the medial septum

The prolonged maintenance of hippocampal long-term potentiation (LTP) seems to require heterosynaptic events during its induction. We have previously shown that stimulation of the basolateral nucleus of the amygdala (BLA) within a distinct time window can reinforce a transient early-LTP into a long-lasting late-LTP in the dentate gyrus (DG) in freely moving rats. We have shown that this reinforcement was dependent on beta-adrenergic and/or muscarinergic receptor activation and protein synthesis. However, since the BLA does not directly stimulate the DG the question remained by which inputs such heterosynaptic processes are triggered. We have now directly stimulated the medial septal pathway 15 min after induction of early-LTP in the DG and show that this input is capable of reinforcing early into late-LTP in a frequency-dependent manner. This septal reinforcement of DG LTP was dependent on beta-adrenergic receptor activation and protein synthesis. We suggest that the reinforcing effect of the BLA stimulation can, potentially, be mediated via the septal input to the DG, though it differs in its ability to induce or modulate functional plasticity.     

Synaptic plasticity in the amygdala in a visceral pain model in rats

The amygdala plays a key role in the emotional-affective component of pain. This study is the first to analyze synaptic plasticity in the central nucleus of the amygdala (CeA) in a model of visceral pain. Whole-cell patch-clamp recordings were made from neurons in the latero-capsular part of the CeA in brain slices from control rats and rats with zymosan-induced colitis (>6 h postinduction). Monosynaptic responses were evoked by electrical stimulation of afferents from the pontine parabrachial area (PB) and from the basolateral amygdala (BLA). Enhanced synaptic transmission was observed at the nociceptive PB-CeA synapse, but not at the polymodal BLA-CeA synapse, in rats with colitis. The frequency of action potentials evoked by direct current injection was increased in CeA neurons from colitis rats, suggesting enhanced neuronal excitability. Our results provide novel evidence for an important role of the CeA in visceral pain.