Comparison of short- versus long-term ketogenic diet for intractable infantile spasms

Purpose: To compare the prognoses between short‐term (8 months) and conventional long‐term (>2 years) trials involving patients with refractory infantile spasms who successfully completed the ketogenic diet (KD). Methods: Of 40 patients who achieved seizure‐free outcomes and showed improvement in hypsarrhythmic patterns within 6 months of the KD, with a 3:1 fat to nonfat ratio as an add‐on treatment, 16 patients were randomized into the short‐term trial group and the diet was tapered throughout two additional months. Twenty‐four patients were randomized into a long‐term trial group, and 19 patients could successfully discontinue the diet after 2 years. Primary outcome measures included seizure relapse and frequency of 35 patients for >12 months after successful completion of the KD. Key Findings: Of 16 patients in the short‐term trial group, two patients relapsed with clusters of spasms, and one patient had recurrence of occasional focal seizures. Of 19 patients in the long‐term trial group, two patients progressed to Lennox‐Gastaut syndrome and one patient experienced recurrence of occasional focal seizures with secondary generalization. An early response to the KD, evidenced by short latency before seizure freedom and disappearance of hypsarrythmia and cryptogenic etiology, may indicate a successful early discontinuation of the KD. Significant growth failure was complicated only in conventional long‐term trial group. Significance: Use of the KD for only 8 months in children who become spasm‐free appears to be justified, with similar outcomes, recurrence rate, and less growth disturbance than a longer‐term, traditional use.     

Binding deficits in visual short‐term memory in patients with temporal lobe lobectomy

Classical views of the medial temporal lobe (MTL) have established that it plays a crucial role in long‐term memory (LTM). Here we demonstrate, in a sample of patients who have undergone anterior temporal lobectomy for the treatment of pharmacoresistant epilepsy, that the MTL additionally plays a specific, causal role in short‐term memory (STM). Patients (n=22) and age‐matched healthy control participants (n=26) performed a STM task with a sensitive continuous report measure. This paradigm allowed us to examine recall memory for object identity, location and object‐location binding, independently on a trial‐by‐trial basis. Our findings point to a specific involvement of MTL in object‐location binding, but, crucially, not retention of either object identity or location. Therefore the MTL appears to perform a specific computation: binding disparate features that belong to a memory. These results echo findings from previous studies, which have identified a role for the MTL in relational binding for LTM, and support the proposal that MTL regions perform such a function for both STM and LTM, independent of the retention duration. Furthermore, these findings and the methodology employed here may provide a simple, sensitive and clinically valuable means to test memory dysfunuction in MTL disorders.     

Synaptic plasticity in rat subthalamic nucleus induced by high-frequency stimulation

The technique of deep brain stimulation (DBS) has become a preferred surgical choice for the treatment of advanced Parkinson's disease. The subthalamic nucleus (STN) is presently the most promising target for such DBS. In this study, whole-cell patch-clamp recordings were made from 46 STN neurons in rat brain slices to examine the effect of high-frequency stimulation (HFS) of the STN on glutamatergic synaptic transmission in STN neurons. HFS, consisting of trains of stimuli at a frequency of 100 Hz for 1 min, produced three types of synaptic plasticity in 17 STN neurons. First, HFS of the STN induced short-term potentiation (STP) of evoked postsynaptic current (EPSC) amplitude in four neurons. STP was associated with a reduction in the EPSC paired-pulse ratio, suggesting a presynaptic site of action. Second, HFS of the STN generated long-term potentiation (LTP) of EPSC amplitude in eight neurons. Although the EPSC paired-pulse ratio was reduced transiently in the first 2 min following HFS, ratios measured 6-20 min after HFS were unchanged from control. This suggests that LTP is maintained by a postsynaptic mechanism. Third, HFS produced long-term depression (LTD) of EPSC amplitude in five STN neurons. LTD was associated with a significant increase in EPSC paired-pulse ratios, indicating a presynaptic site of action. These results suggest that HFS can produce long-term changes in the efficacy of synaptic transmission in the STN. HFS-induced synaptic plasticity might be one mechanism underlying the effectiveness of DBS in the STN as a treatment of advanced Parkinson's disease.     

Exploring the short term visual store in schizophrenia using the attentional blink

Schizophrenia patients exhibit numerous deficits on visual processing tasks, ranging from very early stages of visual processing (e.g., backward masking) to the later working memory stages (e.g., delayed match-to-sample, N-back). However, little is known about deficits in an intermediate stage of visual information processing, namely short term visual memory (STVM). The attentional blink (AB) paradigm is considered to be a valid way to assess the STVM, and recent studies have reported AB deficits in schizophrenia. However, it is not clear whether the reported AB deficit in schizophrenia patients is due to their increased susceptibility to backward masking or increased vulnerability in the STVM. In this study we first found poorer performance in the AB task in 37 schizophrenia patients compared to 26 normal controls. To examine the effects of increasing and decreasing mask strength on AB performance in patients and controls, we next systematically varied the masking effect by varying the length of the distracters immediately following the targets. The manipulation had relatively little effect on the patient--control differences and patients continued to show an enhanced AB effect across conditions. The findings suggest that the enhanced AB effect in schizophrenia reflects an abnormality in their short term visual memory, as opposed to their enhanced susceptibility to visual masking.     

Metaplasticity of the human trigeminal blink reflex

Although synaptic plasticity in the human cerebral cortex is governed by metaplasticity, whether a similar mechanism operates at brainstem level is unknown. In this study in healthy humans we examined the effects and interactions induced by pairing supraorbital nerve high-frequency electrical stimulation (HFS) protocols on the R2 component of the trigeminal blink reflex [Mao, J.B. & Evinger, C (2001) J Neurosci., 21:RC151(1-4)]. Changes in the R2 component were tested by pairing three different priming stimulation protocols inducing long-term potentiation (LTP)-like or long-term depression (LTD)-like effects (LTP-HFS and LTD-HFS), or no change (CONTROL-HFS) with a subsequent test LTP-HFS. Additionally, to examine changes in the R2 component induced by nonspecific factors, two CONTROL-HFS sessions were paired. Priming LTP-, LTD- or CONTROL-HFS potentiated, inhibited or left unchanged the area of the R2 component. Regardless of the type of priming LTP-, LTD- or CONTROL-HFS, the test LTP-HFS induced negligible differences in the R2 component. When two CONTROL-HFS sessions were paired, the test CONTROL-HFS increased the latency and markedly reduced the duration and area of the R2 component. The analysis of the normalized data across the first three experimental sessions, corrected for the inhibitory effects found in the fourth experiment, showed that the test LTP-HFS potentiated the R2 component area of the trigeminal blink reflex only when preceded by a priming LTD-HFS. We propose that homosynaptic metaplasticity might operate in the brainstem circuitry of the blink reflex.     

Do fibromyalgia patients benefit from cognitive restructuring and acceptance? An experimental study

Background and objectivesThe aim of this study was to clarify mechanisms of psychological fibromyalgia treatment by experimentally examining the effectiveness of its core elements. We assessed the effects of cognitive restructuring and acceptance on experimentally-induced heat and cold pain tolerance and pain intensity in fibromyalgia patients.MethodsCold and heat pain were induced in a sample of 60 fibromyalgia patients using a thermode. We conducted ANCOVAs to examine group differences in posttest scores, co-varying for pretest scores. The between-groups factor was the type of instruction provided (acceptance, cognitive restructuring, and a control condition). In addition, we controlled for pain sensitivity, age, and depression.ResultsWe found that acceptance and cognitive restructuring were superior to the control condition in increasing heat pain tolerance, but did not differ from one another. With respect to cold pain tolerance, cognitive restructuring was associated with increases in cold pain tolerance compared to the control condition, while acceptance did not differ either from the control condition or from cognitive restructuring.LimitationsFurther experimental research on chronic pain treatment mechanisms is needed, particularly research on individually tailoring treatment strategies according to patients characteristics. Conclusion: Results show that both, cognitive restructuring and acceptance instructions, enhance pain tolerance in fibromyalgia patients.     

The effects of intra‐hippocampal L‐thyroxine infusion on long‐term potentiation and long‐term depression: A possible role for the αvβ3 integrin receptor

Although the effects of long‐term experimental dysthyroidism on long‐term potentiation (LTP) and long‐term depression (LTD) have been documented, the relationship between LTP/LTD and acute administration of L‐thyroxine (T4) has not been described. Here, we investigated the effects of intra‐hippocampal administration of T4 on synaptic plasticity in the dentate gyrus of the hippocampal formation. After a 15‐minute baseline recording, LTP and LTD were induced by application of high‐ and low‐frequency stimulation protocols, respectively. Infusions of saline or T4 and tetraiodothyroacetic acid (tetrac), a T4 analog that inhibits binding of iodothyronines to the integrin αvβ3 receptor, either alone or together, were made during the stimulation protocols. The averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes, between 55 to 60 minutes, were used as a measure of the LTP/LTD magnitude and were analyzed by two‐way univariate ANOVA with T4 and tetrac as between‐subjects factors. The input–output curves of the infusion groups were comparable to each other, as shown by the non significant interaction observed between stimulus intensity and infused drug. The magnitude of the LTP in T4‐infused rats was significantly lower as compared to saline‐infused rats. Both the PS amplitude and the EPSP slope were depressed more markedly with T4 infusion than with saline, tetrac, and T4 + tetrac infusion. Data of this study provide in vivo evidence that T4 can promote LTD over LTP via the integrin αvβ3 receptor, and that the effect of endogenous T4 on this receptor can be suppressed by tetrac in the hippocampus. © 2016 Wiley Periodicals, Inc.     

Differential roles of basolateral and central amygdala on the effects of uncontrollable stress on hippocampal synaptic plasticity

The amygdala is considered central in mediating stress-related changes of hippocampal functions. However, it remains unclear whether different amygdala subnuclei have different roles in coordinating stress effects. Here, we report that stress exposure caused an immediate increase of extracellular signal-regulated kinase (ERK)1/2 phosphorylation in the hippocampal area CA1 and the basolateral amygdala (BLA) and after a delay in the central amygdala (CEA). Exposure to the novel environment following stress increased ERK1/2 phosphorylation in the CEA, but reversed the stress-induced increase of ERK1/2 phosphorylation in the hippocampal area CA1 and the BLA. Either ERK1/2 inhibitor U0126 or N-methyl-D-aspartate (NMDA) receptor antagonist DL-(-)-2-amino-5-phosphonopentanoic acid (APV) administration into the BLA, but not the CEA, blocked the stress effects on hippocampal long-term potentiation (LTP) and long-term depression. Novelty-exploration-induced reversal of stress effects was prevented when animals were injected U0126 or APV into the CEA, but not the BLA, before subjected to the novel environment. The ability of novelty exploration to reverse the stress effects was mimicked by intra-CEA infusion of NMDA. These findings suggest that BLA ERK1/2 signaling pathway is critical to mediate the stress effects on hippocampal synaptic plasticity; the activation of CEA ERK1/2, in contrast, appears to mediate the reversal of stress effects.     

Hippocampal long‐term potentiation that is elicited by perforant path stimulation or that occurs in conjunction with spatial learning is tightly controlled by beta‐adrenoreceptors and the locus coeruleus

The noradrenergic system, driven by locus coeruleus (LC) activation, plays a key role in the regulating and directing of changes in hippocampal synaptic efficacy. The LC releases noradrenaline in response to novel experience and LC activation leads to an enhancement of hippocampus‐based learning, and facilitates synaptic plasticity in the form of long‐term depression (LTD) and long‐term potentiation (LTP) that occur in association with spatial learning. The predominant receptor for mediating these effects is the β‐adrenoreceptor. Interestingly, the dependency of synaptic plasticity on this receptor is different in the hippocampal subfields whereby in the CA1 in vivo, LTP, but not LTD requires β‐adrenoreceptor activation, whereas in the mossy fiber synapse LTP and LTD do not depend on this receptor. By contrast, synaptic plasticity that is facilitated by spatial learning is highly dependent on β‐adrenoreceptor activation in both hippocampal subfields. Here, we explored whether LTP induced by perforant‐path (pp) stimulation in vivo or that is facilitated by spatial learning depends on β‐adrenoreceptors. We found that under both LTP conditions, antagonising the receptors disabled the persistence of LTP. β‐adrenoreceptor‐antagonism also prevented spatial learning. Strikingly, activation of the LC before high‐frequency stimulation (HFS) of the pp prevented short‐term potentiation but not LTP, and LC stimulation after pp‐HFS‐induced depotentiation of LTP. This depotentiation was prevented by β‐adrenoreceptor‐antagonism. These data suggest that β‐adrenoreceptor‐activation, resulting from noradrenaline release from the LC during enhanced arousal and learning, comprises a mechanism whereby the duration and degree of LTP is regulated and fine tuned. This may serve to optimize the creation of a spatial memory engram by means of LTP and LTD. This process can be expected to support the special role of the dentate gyrus as a crucial subregional locus for detecting and processing novelty within the hippocampus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Exploring strategies to alleviate caregiver burden: Effects of the National Long‐Term Care insurance scheme in Japan

The ever‐increasing population of older people with disabilities, including dementia, has been accompanied by a corresponding growth in the number of family caregivers, who are themselves at risk of developing mental and physical health problems. As a result, the need for practical and effective approaches for alleviating caregiver burden has become a major public health concern. One approach involves the development of public policy initiatives to allow the caregiver burden to be borne partly by society as a whole, rather than falling solely on individuals. In 2000, Japan introduced a National Long‐Term Care (LTC) insurance scheme that requires adults over the age of 40 years to pay compulsory monthly premiums, with one aim of the program being to reduce caregiver burden. The present paper reviews the effects of this scheme on caregivers' and the general public's perception of caregiver burden and assesses what other measures are needed to further reduce and/or prevent burden. Drawing on recent studies, four questions are addressed: (i) have caregivers' attitudes towards caregiving changed since the implementation of the scheme; (ii) do services provided under the scheme alleviate caregiver burden; (iii) what are the general public's attitudes to and understanding of family caregiving; and (iv) what is the general public's level of understanding of dementia? Results from recent studies suggest that the LTC insurance scheme in Japan appears to be an effective measure for alleviating the burden of caregiving among current family caregivers, but larger studies are needed to determine overall effectiveness.     

Facilitated CA1 hippocampal synaptic plasticity in dystrophin‐deficient mice: Role for GABAA receptors?

Duchenne muscular dystrophy (DMD) is associated with cognitive deficits that may result from a deficiency in the brain isoform of the cytoskeletal membrane-associated protein, dystrophin. CA1 hippocampal short-term potentiation (STP) of synaptic transmission is increased in dystrophin-deficient mdx mice, which has been attributed to a facilitated activation of NMDA receptors. In this study, extracellular recordings in the hippocampal slice preparation were used first to determine the consequences of this alteration on short-term depression (STD). STD induction was facilitated in mdx as compared with wild-type mice in a control medium. Because brain dystrophin deficiency results in a decreased number of gamma-aminobutyric acid A (GABAA)-receptor clusters, we tested the hypothesis that neuronal disinhibition contributes to the enhanced synaptic plasticity in mdx mice. We found that the GABAA receptor antagonist, bicuculline, increased basal neurotransmission in wild-type, but not in mdx mice and prevented the enhanced STP and STD in the CA1 area of slices from mdx mice. The possibility that altered GABA mechanisms underlie the facilitation of NMDA receptor-dependent synaptic plasticity in mdx mice is discussed.     

Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats

Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as attention, learning, and memory, but the synaptic alterations underlying these deficits remain unexplored. The present study examines the effect of congenital hypothyroidism on long-term synaptic plasticity. This plasticity is believed to be essential for learning and memory and for activity-dependent regulation of synapse formation in the developing brain. We found that the neonatal expression of long-term potentiation (LTP), long-term depression (LTD), depotentiation, and de-depression in hippocampal slices from hypothyroid animals was similar to that of controls. To examine the postnatal development of these plasticities, we used slices from neonatal (2-3 weeks) and adult (7-8 weeks) rats. This work demonstrates that the ability to express all these forms of synaptic plasticity is reduced in an age-dependent manner in control rats. LTP and depotentiation are also downregulated in adult hypothyroid rats, but we have found that de-depression is not affected during maturation. In addition, these animals express LTD at ages at which controls fail to induce it. In contrast, input/output experiments have shown greater levels of basal synaptic efficacy in hypothyroid adults, and this effect is probably related to the higher probability of release observed by paired-pulse experiments. Nevertheless, these effects appear to be unrelated to the differences observed in long-term synaptic plasticity, as no correlation was found between basal synaptic efficacy and the degree of LTD and de-depression. Furthermore, the NMDA-receptor antagonist amino-phosphonopentanoic acid (APV) completely blocked LTD, which suggests a postsynaptic locus of this alteration. Because LTD has been associated with novelty acquisition, we suggest that the greater LTD observed in adult hypothyroid rats might be related to the hyperactivity of these animals. However, other possibilities such as a retarded maturation of synaptic plasticity must be taken into account.     

Alterations in the balance of protein kinase and phosphatase activities and age-related impairments of synaptic transmission and long-term potentiation

Aging is associated with an impaired ability to maintain long-term potentiation (LTP), but the underlying cause of the impairment remains unclear. To gain a better understanding of the cellular and molecular mechanisms responsible for this impairment, the synaptic transmission and plasticity were studied in the CA1 region of hippocampal slices from adult (6-8 months) and poor-memory (PM)-aged (23-24 months) rats. The one-way inhibitory avoidance learning task was used as the behavioral paradigm to screen PM-aged rats. With intracellular recordings, CA1 neurons of PM-aged rats exhibited a more hyperpolarized resting membrane potential, reduced input resistance, and increased amplitude of afterhyperpolarization and spike threshold, compared with those in adult rats. Although a reduction in the size of excitatory synaptic response was observed in PM-aged rats, no obvious differences were found between adult and PM-aged rats in the pharmacological properties of excitatory synaptic response, paired-pulse facilitation, or frequency-dependent facilitation, which was tested with trains of 10 pulses at 1, 5, and 10 Hz. Slices from the PM-aged rats displayed significantly reduced early-phase long-term potentiation (E-LTP) and late-phase LTP (L-LTP), and the entire frequency-response curve of LTP and LTD is modified to favor LTD induction. The susceptibility of time-dependent reversal of LTP by low-frequency afferent stimulation was also facilitated in PM-aged rats. Bath application of the protein phosphatase inhibitor, calyculin A, enhanced synaptic response in slices from PM-aged, but not adult, rats. In contrast, application of the cAMP-dependent protein kinase inhibitors, Rp-8-CPT-cAMPS and KT5720, induced a decrease in synaptic transmission only in slices from the adult rats. Furthermore, the selective beta-adrenergic receptor agonist, isoproterenol, and pertussis toxin-sensitive G-protein inhibitor, N-ethylmaleimide, effectively restored the deficit in E-LTP and L-LTP of PM-aged rats. These results demonstrate that age-related impairments of synaptic transmission and LTP may result from alterations in the balance of protein kinase/phosphatase activities.     

肌注氟哌啶醇合用利培酮对精神分裂症急性期激越行为疗效的研究

目的探讨肌注氟哌啶醇合用利培酮对急性期精神分裂症患者激越行为的疗效。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)诊断标准的165名新入院伴有兴奋冲动行为的精神分裂症患者,采用随机数字表法分为3组,利培酮合并氟哌啶醇组(A组)、利培酮合并氯硝西泮组(B组)和氟哌啶醇组(C组),观察2周。采用阳性及阴性评定量表(PANSS)兴奋激越因子评定精神症状(激越行为)。结果 PANSS-兴奋激越各单项分的时间因素主效应均具有统计学意义(F=896.936~1484.087,P0.01),且时间与治疗因素之间交互效应均有统计学意义(F=6.962~41.495,P0.01)。治疗因素主效应仅在敌对单项分上有统计学意义(F=3.455,P=0.034)。重复测量方差分析显示,3组患者组内不同时间点各单项得分比较,差异有统计学意义(F=227.991~615.334,P0.01)。3组患者组间各单项分多元方差分析表明,治疗前:差异无统计学意义(F=0.073~1.473,P0.05);治疗后24h末:差异均有统计学意义(F=5.386~8.075,P0.01);1周末:除愤怒、延迟满足困难外,差异均有统计学意义(F=7.357~8.546,P0.01);2周末,除兴奋外,差异无统计学意义(F=0.616~1.205,P0.05)。结论利培酮合并氟哌啶醇短期肌注可作为临床处理精神分裂症急性期兴奋激越手段之一。     

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation (LTP) was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber B (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD.     

重型颅脑损伤患者外周血miR-122-5p表达水平变化及其对近期预后的预测价值

目的 探讨重型颅脑损伤(sTBI)患者外周血miR-122-5p表达水平变化及其对近期预后的预测价值.方法 选择2016年3月-2019年8月本院收治的sTBI患者作为sTBI组,同期体检的健康志愿者作为对照组,检测外周血miR-122-5p的表达水平;随访sTBI组的近期预后并分为死亡患者和好转患者,分析预后的影响因...     

Acute stress disrupts paired pulse facilitation and long‐term potentiation in rat dorsal hippocampus through activation of glucocorticoid receptors

Cognitive functions such as learning and memory are widely believed to depend on patterns of short‐ and long‐term synaptic plasticity. Factors, such as acute stress, which affect learning and memory, may do so by altering patterns of synaptic plasticity in distinct neural circuits. Numerous studies have examined the effects of acute stress on long‐term synaptic plasticity; however, few have examined its influence on short‐term plasticity. The present experiments directly assessed the effects of acute stress on short‐term synaptic plasticity as measured by paired pulse facilitation (PPF) of excitatory postsynaptic potentials recorded from rat dorsal hippocampus (dHip) in vivo. Long‐term potentiation (LTP) was also examined. Acute stress induced by exposure to an elevated platform impaired PPF and LTP in the dHip. Pretreatment of rats exposed to stress with mifepristone (RU38486; 10 mg kg⁻¹) blocked the stress‐induced impairment of both PPF and LTP. These data demonstrate that activation of glucocorticoid receptors during acute stress disrupts normal patterns of both PPF and LTP in the dHip. © 2009 Wiley‐Liss, Inc.     

Chronic in vivo optogenetic stimulation modulates neuronal excitability,spine morphology,and Hebbian plasticity in the mouse hippocampus

Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.