Field Excitatory Postsynaptic Potentials Research Articles

흰쥐 해마 CA1 영역에서 H₂O₂에 의한 장기강화 억제에 대한 발효황금 추출물의 효과

Scutellaria baicalensis (SB) has widely used in the treatment for various brain diseases in the field of Oriental medicine. Biofermantation of SB can make major chemical constituents of SB to pass blood-brain barrier easily and to have more potent anti-oxidant ability. There is a little information about the contribution of fermented SB (FSB) to the formation or maintenance of the neural plasticity in the hippocampus. The purpose of this study was to evaluate effects of FSB extract on hydrogen peroxide (H₂O₂) - induced impairments of the induction and maintenance of long-term potentiation (LTP), an electrophysiological marker for the neural plasticity in the hippocampus. From hippocampal slices of rats, the field excitatory postsynaptic potentials (fEPSPs) were evoked by the electrical stimulation to the Schaffer collaterals - commissural fibers in the CA1 areas and LTP by theta-burst stimulation by using 64 - channels in vitro multi-extracellular recording system. In order to induce oxidative stress to hippocampal slices two different concentrations (200, 400 μM) of H₂O₂ were given to the perfused aCSF before and after the LTP induction, respectively. The ethanol extract of FBS with concentration of 25 ㎍/ml, 50 ㎍/ml was diluted in perfused aCSF that had 200 μM H₂O₂, respectively. Oxidative stress by the treatment of H₂O₂ resulted in decrease of the induction rate of LTP in the CA1 area with a dose - dependent manner. However, the ethanol extract of FSB prevented the reduction of the induction rate of LTP caused by H₂O₂ - induced oxidative stress with a dose - dependent manner. These results may support a potential application of FSB to ameliorate impairments of hippocampal dependent neural plasticity or memory caused by oxidative stress.

Effects of Chronic Aluminum Lactate Exposure on Neuronal Apoptosis and Hippocampal Synaptic Plasticity in Rats.

This study investigated the effects of chronic aluminum exposure on apoptosis of hippocampal neurons, and synaptic plasticity in the hippocampus in rats. Rats were divided into the control, low-dose (L-Al), mid-dose (M-Al), and high-dose (H-Al) groups. After chronic exposure of aluminum, the Morris water maze (MWM) and open-field (OF) tests were performed to assess the behavioral performance. Electrophysiological measurements were conducted. Flow cytometry was used to assess the apoptotic processes. Quantitative real-time PCR and ELISA were performed to measure mRNA and protein expression levels of caspases. After 90days of aluminum exposure, the aluminum contents in the brain of the rats were increased, with the increasing exposure dose. The MWM and OF tests showed that chronic exposure of aluminum significantly impaired the neurobehavior of rats. Moreover, after high-frequency stimulation (HFS), the average amplitudes of field excitatory postsynaptic potentials (fEPSPs) for the M-Al and H-Al groups were lower than the control group at 10, 20, 30, 40, 50, and 60min. Furthermore, the apoptotic rates in the M-Al and H-Al groups were significantly higher than the control group. The qRT-PCR and ELISA showed that, compared with the control group, the mRNA and protein expression levels of caspases-3, -8, and -9 were significantly increased in the aluminum-treated groups compared with the control group. Long-term exposure to aluminum could induce the apoptosis of hippocampal neurons, damage the synaptic plasticity, and impair the learning and memory functions in rats. There might be a close relationship between the neuronal apoptosis and synaptic plasticity damage.

Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice

Activated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human Caspase-6 in hippocampal CA1 neurons develop age-dependent cognitive deficits, neurodegeneration and neuroinflammation. This study assessed if methylene blue (MB), a phenothiazine that inhibits caspases, alters Caspase-6-induced neurodegeneration and cognitive impairment in mice. Aged cognitively impaired Casp6-overexpressing mice were treated with methylene blue in drinking water for 1 month. Methylene blue treatment did not alter Caspase-6 levels, assessed by RT-PCR, western blot and immunohistochemistry, but inhibited fluorescently-labelled Caspase-6 activity in acute brain slice intact neurons. Methylene blue treatment rescued Caspase-6-induced episodic and spatial memory deficits measured by novel object recognition and Barnes maze, respectively. Methylene blue improved synaptic function of hippocampal CA1 neurons since theta-burst long-term potentiation (LTP), measured by field excitatory postsynaptic potentials (fEPSPs) in acute brain slices, was successfully induced in the Schaffer collateral-CA1 pathway in methylene blue-treated, but not in vehicle-treated, Caspase-6 mice. Increased neuroinflammation, measured by ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia numbers and subtypes, and glial fibrillary acidic protein (GFAP)-positive astrocytes, were decreased by methylene blue treatment. Therefore, methylene blue reverses Caspase-6-induced cognitive deficits by inhibiting Caspase-6, and Caspase-6-mediated neurodegeneration and neuroinflammation. Our results indicate that Caspase-6-mediated damage is reversible months after the onset of cognitive deficits and suggest that methylene blue could benefit Alzheimer disease patients by reversing Caspase-6-mediated cognitive decline.

Aluminium-induced synaptic plasticity injury via the PHF8-H3K9me2-BDNF signalling pathway.

Aluminium is an environmental neurotoxin that comes extensively in contact with human being. The molecular mechanism of aluminium toxicity remains unclear. A number of studies have indicated that exposure to aluminium can impair learning and memory function. The purpose of this study was to investigate the mechanism of long-term potentiation(LTP) injury and the related signalling pathway activated by aluminium exposure. The results showed that aluminium treatment produced dose-dependent inhibition of LTP and reduced the activity of Histone H3K9 demethylation (H3K9me2) demethylase and the expression of the PHD (plant homeodomain) finger protein 8 (PHF8). Interestingly, there was no statistically significant difference in the expression of the PHF8 gene, suggesting that aluminium exposure only affects the translation process. Decrease in brain-derived neurotrophic factor (BDNF) expression may be related to the effect of aluminium. With correlation analysis between the hippocampal standardised field excitatory postsynaptic potential (fEPSP) amplitude and the expression of various proteins in the aluminium-exposed rat, the hippocampal standardised fEPSP amplitude was positively correlated with the expression of hippocampal PHF8 and BDNF proteins, and negatively correlated with the expression of hippocampal H3K9me2 protein. The correlation between H3K9me2 and BDNF was also considered negative. The results suggest that changes in synaptic plasticity might be related to changes in these proteins, which were induced by aluminium exposure. In conclusion, chronic aluminium exposure may inhibit PHF8 and prevent it from functioning as a demethylase. This may block H3K9me2 demethylation, decrease BDNF protein expression, and lead to LTP impairment.

MicroRNA-34a Acutely Regulates Synaptic Efficacy in the Adult Dentate Gyrus In Vivo.

Activity-dependent synaptic plasticity involves rapid regulation of neuronal protein synthesis on a time-scale of minutes. miRNA function in synaptic plasticity and memory formation has been elucidated by stable experimental manipulation of miRNA expression and activity using transgenic approaches and viral vectors. However, the impact of rapid miRNA modulation on synaptic efficacy is unknown. Here, we examined the effect of acute (12 min), intrahippocampal infusion of a miR-34a antagonist (antimiR) on medial perforant path-evoked synaptic transmission in the dentate gyrus of adult anesthetised rats. AntimiR-34a infusion acutely depressed medial perforant path-evoked field excitatory post-synaptic potentials (fEPSPs). The fEPSP decrease was detected within 9 min of infusion, lasted for hours, and was associated with knockdown of antimiR-34a levels. AntimiR-34a-induced synaptic depression was sequence-specific; no changes were elicited by infusion of scrambled or mismatch control. The rapid modulation suggests that a target, or set of targets, is regulated by miR-34a. Western blot analysis of dentate gyrus lysates revealed enhanced expression of Arc, a known miR-34a target, and four novel predicted targets (Ctip2, PKI-1α, TCF4 and Ube2g1). Remarkably, antimiR-34a had no effect when infused during the maintenance phase of long-term potentiation. We conclude that miR-34a regulates basal synaptic efficacy in the adult dentate gyrus in vivo. To our knowledge, these in vivo findings are the first to demonstrate acute (< 9 min) regulation of synaptic efficacy in the adult brain by a miRNA.

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats.

Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.

Hypothermia Masks Most of the Effects of Rapid Cycling VNS on Rat Hippocampal Electrophysiology.

AIM. Vagus nerve stimulation (VNS) modulates hippocampal dentate gyrus (DG) electrophysiology and induces hypothermia in freely moving rats. This study evaluated whether hippocampal (CA1) electrophysiology is similarly modulated and to what extent this is associated with VNS-induced hypothermia. METHODS. Six freely moving rats received a first 4h session of rapid cycling VNS (7s on/18s off), while CA1 evoked potentials, EEG and core temperature were recorded. In a second 4h session, external heating was applied during the 3rd and 4thh of VNS counteracting VNS-induced hypothermia. RESULTS. VNS decreased the slope of the field excitatory postsynaptic potential (fEPSP), increased the population spike (PS) amplitude and latency, decreased theta (4-12Hz) and gamma (30-100Hz) band power and theta peak frequency. Normalizing body temperature during VNS through external heating abolished the effects completely for fEPSP slope, PS latency and gamma band power, partially for theta band power and theta peak frequency and inverted the effect on PS amplitude. CONCLUSIONS. Rapid cycle VNS modulates CA1 electrophysiology similarly to DG, suggesting a wide-spread VNS-induced effect on hippocampal electrophysiology. Normalizing core temperature elucidated that VNS-induced hypothermia directly influences several electrophysiological parameters but also masks a VNS-inducedreduction in neuronal excitability.

Self-powered, wireless-control, neural-stimulating electronic skin for in vivo characterization of synaptic plasticity

Synaptic plasticity underlies brain changes when learning or memory takes place. Long-term memory requires modification of synaptic strengths between neurons. The characterization of the synaptic changes therefore reflects the long term storage of information in the brain structures. Traditionally, electrical neural-stimulating technique for characterizing synaptic plasticity requires external power source and steer-by-wire system. Here, a novel self-powered, wireless-control, neural-stimulating electronic skin (e-skin) for in vivo characterization of synaptic plasticity has been presented. The e-skin is composed of flexible photosensitive-triboelectric MAPbI3/PDMS units. The outputting electrical neural-stimulating signal of the e-skin is generated by human body activities without any batteries, and the neural-modulation can be controlled by photo illumination on/off as wireless switch. To demonstrate the application of the e-skin in characterizing synaptic changes, we connect the device to the hippocampus of the mouse brain. The e-skin neural stimulating in the CA3 of mouse hippocampus and simultaneous recording field excitatory postsynaptic potentials (fEPSP) in the CA1 demonstrate that the e-skin can successfully elicit post-synaptic responses for in vivo characterization of synaptic plasticity. This self-powered photo-operate e-skin can provoke a new research direction for realizing battery-free, wireless-control, electrical neural-stimulating systems with implications in biomedical engineering and neural science.

Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease

AimsGlutamatergic dysfunction is posed as a main stage in neurodegenerative disorders such as Alzheimer's disease (AD). Glutamate-mediated excitotoxicity contributes to cognitive dysfunction and cell death in AD. Ceftriaxone (CFT), a well-known upregulator of GLT-1, selectively induces the expression of glutamate transporter-1 (GLT-1) in different brain regions and therefore can be posed as a potential candidate for elimination of glutamate-induced excitotoxicity which is an early prominent event in AD brains. This study was designed to investigate the electrophysiological and behavioral effects of the β-lactam antibiotic ceftriaxone in okadaic acid (OKA)-induced model of AD. Materials and methodsMale Wistar rats divided into four control, ceftriaxone (CFT), OKA, and OKA plus ceftriaxone (OKA + CFT) groups. OKA was injected intracerebroventricularly (i.c.v., 200 ng/5 μl) into lateral ventricles and after two weeks the evoked field potential recorded from hippocampal perforant path-DG synapses in order to evaluate the effect of ceftriaxone treatment (200 mg/kg/day, i.p.) on long-term potentiation (LTP) and paired-pulse responses. Key findingsResults of this study revealed that ceftriaxone treatment significantly ameliorates the OKA-induced attenuation of field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude following high-frequency stimulation and paired-pulse paradigm indicating its beneficial effects on both short-term and long-term plasticity in these neurons. Ceftriaxone also has an improving effect on OKA-induced impairment in short- and long-term memories evaluated by alternation behavior and passive avoidance tasks in rats. SignificanceTherefore, this study suggests that GLT-1 might be a promising therapeutic target for treatment of neurodegenerative disorders such as AD in the future.

Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice.

Binge drinking is a significant problem in adolescent populations, and because of the reciprocal interactions between ethanol (EtOH) consumption and the endocannabinoid (eCB) system, we sought to determine if adolescent EtOH intake altered the localization and function of the cannabinoid 1 (CB1) receptors in the adult brain. Adolescent mice were exposed to a 4-day-per week drinking in the dark (DID) procedure for a total of 4 weeks and then tested after a 2-week withdrawal period. Field excitatory postsynaptic potentials (fEPSPs), evoked by medial perforant path (MPP) stimulation in the dentate gyrus molecular layer (DGML), were significantly smaller. Furthermore, unlike control animals, CB1 receptor activation did not depress fEPSPs in the EtOH-exposed animals. We also examined a form of excitatory long-term depression that is dependent on CB1 receptors (eCB-eLTD) and found that it was completely lacking in the animals that consumed EtOH during adolescence. Histological analyses indicated that adolescent EtOH intake significantly reduced the CB1 receptor distribution and proportion of immunopositive excitatory synaptic terminals in the medial DGML. Furthermore, there was decreased binding of [35S]guanosine-5*-O-(3-thiotriphosphate) ([35S] GTPγS) and the guanine nucleotide-binding (G) protein Gαi2 subunit in the EtOH-exposed animals. Associated with this, there was a significant increase in monoacylglycerol lipase (MAGL) mRNA and protein in the hippocampus of EtOH-exposed animals. Conversely, deficits in eCB-eLTD and recognition memory could be rescued by inhibiting MAGL with JZL184. These findings indicate that repeated exposure to EtOH during adolescence leads to long-term deficits in CB1 receptor expression, eCB-eLTD, and reduced recognition memory, but that these functional deficits can be restored by treatments that increase endogenous 2-arachidonoylglycerol.

Structural Evaluation and Electrophysiological Effects of Some Kynurenic Acid Analogs.

Kynurenic acid (KYNA), a metabolite of tryptophan, as an excitatory amino acid receptor antagonist is an effective neuroprotective agent in case of excitotoxicity, which is the hallmark of brain ischemia and several neurodegenerative processes. Therefore, kynurenine pathway, KYNA itself, and its derivatives came into the focus of research. During the past fifteen years, our research group has developed several neuroactive KYNA derivatives, some of which proved to be neuroprotective in preclinical studies. In this study, the synthesis of these KYNA derivatives and their evaluation with divergent molecular characteristics are presented together with their most typical effects on the monosynaptic transmission in CA1 region of the hippocampus of the rat. Their effects on the basic neuronal activity (on the field excitatory postsynaptic potentials: fEPSP) were studied in in vitro hippocampal slices in 1 and 200 μM concentrations. KYNA and its derivative 4 in both 1 and 200 μM concentrations proved to be inhibitory, while derivative 8 only in 200 μM decreased the amplitudes of fEPSPs. Derivative 5 facilitated the fEPSPs in 200 μM concentration. This is the first comparative study which evaluates the structural and functional differences of formerly and newly developed KYNA analogs. Considerations on possible relations between molecular structures and their physiological effects are presented.

Acupuncture Improves Comorbid Cognitive Impairments Induced by Neuropathic Pain in Mice.

Growing evidence indicates that neuropathic pain is frequently accompanied by cognitive impairments, which aggravate the quality of life of chronic pain patients. Here, we investigated whether acupuncture treatments can improve cognitive dysfunction as well as allodynia induced by neuropathic pain in mice. One week after the left partial sciatic nerve ligation (PSNL), acupuncture treatments on the acupoints GB30-GB34 (AP1), HT7-GV20 (AP2), or control points (CP) were performed for 4 weeks. Notably, the significant attenuations of mechanical allodynia and cognitive impairment were observed in the AP1 group, but not in PSNL, AP2, or CP groups. A random decision forest classifier based on the pain and cognitive functions displayed that the acupuncture group was clearly segregated from the other groups. We also demonstrated that acupuncture restored the reduced field excitatory post-synaptic potentials and was able to elevate the expression levels of glutamate receptors (NR2B and GluR1) in the hippocampus. Moreover, the expressions of Ca2+/calmodulin-dependent protein kinase II and synaptic proteins (pPSD-95 and pSyn-1) were enhanced by acupuncture treatment. These results suggest that acupuncture can enhance hippocampal long-term action through the regulation of the synaptic efficacy and that acupuncture may provide a viable option for managing both pain and cognitive functions associated with chronic neuropathic pain.

Maternal separation impairs long term-potentiation in CA3-CA1 synapses in adolescent female rats

Mother-infant interactions influence the development of physiology and behavior during the first weeks after birth. As an adverse early life experience, maternal separation (MS) produces behavioral and neuroendocrine functions disorders associated with the hippocampus. Considering the critical role of long-term potentiation (LTP) in learning and memory, we investigated whether MS affects LTP in adolescent female rats. In this study, female rat pups were exposed to daily 3-h (MS180) or 15-min (MS15) periods of maternal separation on postnatal days (PND) 1–14 and control offspring remained with the dams all the time before weaning. Extracellular evoked field excitatory postsynaptic potentials (fEPSPs) were recorded in the stratum radiatum of the CA1 area of the slice at 28–35 days of age. Our results indicate that a significant difference existed in the magnitude of LTP between the control group and MS180 group, but the MS15 group was not different from control. In conclusion, these findings suggest that MS may impair LTP induction in the CA1 area of the hippocampus in adolescent female rats.

Intermittent-Excessive and Chronic-Moderate Ethanol Intake during Adolescence Impair Spatial Learning, Memory and Cognitive Flexibility in the Adulthood

Intermittent and excessive ethanol consumption over very short periods of time, known as binge drinking, is common in the adolescence, considered a vulnerable period to the effects of alcohol in terms of cognitive performance. One of the brain functions most drastically affected by ethanol in adolescent individuals seems to be spatial learning and memory dependent on the hippocampus. In the current study we have focused on the long-lasting effects on spatial learning and memory of intermittent and excessive alcohol consumption compared to chronic and moderate alcohol exposure during adolescence. Five-week old male Wistar rats consumed ethanol for 24 days following two different self-administration protocols that differed in the intake pattern. Spatial learning and memory were evaluated in the radial arm maze. Hippocampal synaptic plasticity was assessed by measuring field excitatory postsynaptic potentials. Hippocampal expression of AMPA and NMDA receptor subunits as well as levels of phosphorylated Ser9-GSK3β (the inactive form of GSK3β) were also quantified. Our results show that both patterns of ethanol intake during adolescence impair spatial learning, memory and cognitive flexibility in the adulthood in a dose-dependent way. Nevertheless, changes in synaptic plasticity, gene expression and levels of inactive GSK3β depended on the pattern of ethanol intake.

Behavioral and electrophysiological aspects of cognition in neonate rats lactated by morphine addicted mothers.

Objective(s):In addition to genetic factors, environmental phenomena during postnatal age highly affect development and, in turn, function of the brain. The present work evaluates if morphine consumption during lactation period influences the spatial performances and synaptic plasticity in rats at neonatal period of age. Materials and Methods:Three groups of mothers were subcutaneously administered by 5 (M5), 10 (M10) or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, their offspring were introduced to Morris water maze for assessment of spatial learning and memory. Basic field excitatory post-synaptic potentials (fEPSPs) were recorded in the CA1 area of hippocampus and, then, long term potentiation (LTP) was induced by tetanic stimulation. Results:We found that the M10 and M20 rats spent more time and traveled longer distance to find the hidden platform of maze when compared to the control animals (P<0.05 for all comparisons). Similarly, these two morphine-exposed groups were inferior in the memory consolidation compared to their control counterparts. Comparing control and M20 rats revealed that morphine exposure decreases the mean amplitude and slope 10-90% of fEPSPs about 30 percent (P<0.001 for both comparisons) and inhibits the LTP induction in the CA1 area circuits. Conclusion:The present study provides behavioral and electrophysiological proofs for negative effect of morphine on the hippocampal-related function in the neonatally morphine-exposed rats.

Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer's disease

Studies demonstrate that damage to gut microbiota is associated with some brain disorders including neurodegenerative diseases such as Alzheimer's disease (AD). Accordingly, supporting gut microbiota has been considered as a possible strategy for AD treatment. We evaluated behavioral and electrophysiological aspects of the brain function in an animal model of AD made by intracerebroventricular injection of β-amyloid. Two groups of control rats recieved either water as vehicle (Con) or probitics (Pro + Con). Also two groups of Alzheimeric animals were treated by either vehicle (Alz) or probiotics (Pro + Alz). Sham group was only subjected to surgical procedure and received the vehicle. Spatial learning and memory was assessed in Morris water maze. Also, basic synaptic transmission and long-term potentiation (LTP) were assessed by recording field excitatory postsynaptic potentials (fEPSPs) in hippocampus. Change in anti-oxidant/oxidant factors was assessed via measuring plasma level of total anti-oxidant capacity (TAC) and malondealdehyde (MDA). Brain staining was done to confirm β-amyloid accumulation. Fecal bacteria quantification was accomplished to find how probiotic supplement affected gut microbiota. We found that while the Alz animals displayed a weak spatial performance, probiotic treatment improved the maze navigation in the Pro + Alz rats. Whereas basic synaptic transmission remained unchanged in the Alz rats, LTP was suppressed in this group. Probiotic treatment significantly restored LTP in the Pro + Alz group and further enhanced it in the Pro + Con rats. The intervention also showed a favorable effect on balance of the anti-oxidant/oxidant biomarkers in the Pro + Alz rats. This study provides the first proof on positive effect of probiotics on synaptic plasticity in an animal model of AD.

Investigating Long-term Synaptic Plasticity in Interlamellar Hippocampus CA1 by Electrophysiological Field Recording.

The study of synaptic plasticity in the hippocampus has focused on the use of the CA3-CA1 lamellar network. Less attention has been given to the longitudinal interlamellar CA1-CA1 network. Recently however, an associational connection between CA1-CA1 pyramidal neurons has been shown. Therefore, there is the need to investigate whether the longitudinal interlamellar CA1-CA1 network of the hippocampus supports synaptic plasticity. We designed a protocol to investigate the presence or absence of long-term synaptic plasticity in the interlamellar hippocampal CA1 network using electrophysiological field recordings both in vivo and in vitro. For in vivo extracellular field recordings, the recording and stimulation electrodes were placed in a septal-temporal axis of the dorsal hippocampus at a longitudinal angle, to evoke field excitatory postsynaptic potentials. For in vitro extracellular field recordings, hippocampal longitudinal slices were cut parallel to the septal-temporal plane. Recording and stimulation electrodes were placed in the stratum oriens (S.O) and the stratum radiatum (S.R) of the hippocampus along the longitudinal axis. This enabled us to investigate the directional and layer specificity of evoked excitatory postsynaptic potentials. Already established protocols were used to induce long-term potentiation (LTP) and long-term depression (LTD) both in vivo and in vitro. Our results demonstrated that the longitudinal interlamellar CA1 network supports N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) with no directional or layer specificity. The interlamellar network, however, in contrast to the transverse lamellar network, did not present with any significant long-term depression (LTD).

Adenosine A1 and A2A receptors differently control synaptic plasticity in the mouse dorsal and ventral hippocampus.

The hippocampus is a brain region involved in processing both memory and emotions, through a preferential involvement of the dorsal hippocampus (DH) and ventral hippocampus (VH), respectively. Adenosine A1 and A2A receptors (A1 R and A2A R) control both mood and memory, but it is not known if there is a different adenosine modulation of synaptic plasticity along the hippocampal axis. Using adult, C57BL/6 male mice, we show that both A1 R and A2A R were more abundant in DH compared with VH. However, recordings of field excitatory postsynaptic potentials at Schaffer collaterals-CA1 pyramidal synapses revealed that A1 R were equi-effective to inhibit basal excitatory synaptic transmission in DH and VH, but endogenous A1 R activation was more effective to depress the probability of release in VH. In contrast, the selective A2A R antagonist (SCH58261, 50nM) controlled both long-term potentiation (induced by a high frequency stimulation protocol) and long-term depression (induced by a low frequency stimulation protocol) selectively in DH rather than VH, whereas the selective A1 R antagonist (DPCPX, 100nM) revealed a similar tonic inhibition of long-term depression in DH and VH. These findings show a different control of synaptic plasticity by the adenosine modulation system in the dorsal and ventral poles of the hippocampus, which may underlie a different efficiency of the adenosine system to control mood and memory.

Effects of exposure to extremely low frequency electromagnetic fields on hippocampal long-term potentiation in hippocampal CA1 region

Exposure to environmental electromagnetic fields, especially to the extremely low-frequency (ELF < 300 Hz) electromagnetic fields (EMFs) might produce modulation effects on neuronal activity. Long-term changes in synaptic plasticity such as long-term potentiation (LTP) involved in learning and memory may have contributions to a number of neurological diseases. However, the modulation effects of ELF-EMFs on LTP are not yet fully understood. In our present study, we aimed to evaluate the effects of exposure to ELF-EMFs on LTP in hippocampal CA1 region in rats. Hippocampal slices were exposed to magnetic fields generated by sXcELF system with different frequencies (15, 50, and 100 Hz [Hz]), intensities (0.5, 1, and 2 mT [mT]), and duration (10 s [s], 20 s, 40 s, 60 s, and 5 min), then the baseline signal recordings for 20 min and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded. We found that the LTP amplitudes decreased after magnetic field exposure, and the LTP amplitudes decreased in proportion to exposure doses and durations, suggesting ELF-EMFs may have dose and duration-dependent inhibition effects. Among multiple exposure duration and doses combinations, upon 5 min magnetic field exposure, 15 Hz/2 mT maximally inhibited LTP. Under 15 Hz/2 mT ELF-EMFs, LTP amplitude decreases in proportion to the length of exposure durations within 5 min time frame. Our findings illustrated the potential effects of ELF-EMFs on synaptic plasticity and will lead to better understanding of the influence on learning and memory.

Histone demethylase PHF2 activates CREB and promotes memory consolidation.

Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation are essential for the epigenetic regulation of memory consolidation-related genes. Here, we demonstrate that the plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during the experience phase and plays an essential role in memory formation. PHF2 promotes the expression of memory-related genes by epigenetically reinforcing the TrkB-CREB signaling pathway. In behavioral tests, memory formation is enhanced by transgenic overexpression of PHF2 in mice, but is impaired by silencing PHF2 in the hippocampus. Electrophysiological studies reveal that PHF2 elevates field excitatory postsynaptic potential (fEPSP) and NMDA receptor-mediated evoked excitatory postsynaptic current (EPSC) in CA1 pyramidal neurons, suggesting that PHF2 promotes long-term potentiation. This study provides insight into the epigenetic regulation of learning and memory formation, which advances our knowledge to improve memory in patients with degenerative brain diseases.