Effect of Liuwei Dihuang Decoction (六味地黄汤) on LongTerm Potentiation in Hippocampal Dentate Gyrusin Rats

Objective: To investigate effect of Liuwei Dihuang decoction (LWDHD), a traditional Chinese medicinal prescription, on the formation of long term potentiation (LTP) in the hippocampal dentate gyrus in anesthetized rats. Methods: LTP experiments were conducted by using a bipolar stimulating electrode to stimulate perforant pathway and a monopolar electrode to record the evoked field potential in hippocampal dentate gyrus. In the present study, both suprathreshold and subthreshold tetanic stimulation to the perforant pathway were employed. Results: Single oral administration of LWDHD (per os, 5 g/kg and 10 g/kg respectively) has no effect on the basal spike amplitude. However, LWDHD (per os, 5 g/kg and 10 g/kg respectively) significantly intensified the spike amplitude induced by a subthreshold stimulation (60 Hz, 20 pulses) while it did not affect formation of LTP formation induced by suprathreshold tetanic stimulation (60 Hz, 30 pulses). Conclusion: The present results suggested that LWDHD given orally potentiate the synaptic plasticity and transmission in hippocampal dentate gyrus, which might account for the enhancing effect of LWDHD on learning and memory in senescence accelerated mice.

Oleuropein Improves Long Term Potentiation at Perforant Path-dentate Gyrus Synapses in vivo

Objective To investigate the effect of oleuropein （OE） on long term potentiation （LTP） at hippocampal perforant path-dentate gyrus synapses in vivo. Methods An outer guide cannula, a monopolar recording electrode, and a bipolar stimulating electrode were implanted in the skull and extracellular recording technique was used to record the population spike in the dentate gyrus of anesthetized rats. Results Oleuropein significantly increased the basal synaptic transmission and the amplitude of population spike was increased from （11 7.6 ＋ 2.3）% to （134.9 _＋ 3.7）% after administration with OE. OE also accelerated LTP induction and maintenance, the population spike amplitude after high frequency stimulation was increased from （167.2 ± 12.8）% to （225.5 ± 15.5）% and the maintenance phase of LTP was from （182.1 ± 15.1）% to （210.5 ± 9.0）% respectively after administration with OE. Conclusion Present study showed that OE significantly improved different stages of LTP, which could be the molecular mechanism of its efficacy on attenuating AD-like pathology and delaying cognitive decline. OE can be a promising drug for AD and dementia.

Impacts of Passive Smoking on Learning and Memory Ability of Mouse Offsprings and Intervention by Antioxidants

Objective To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. Methods A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation （LTP）. Nitric oxide （NO）, content, nitric oxide synthase （NOS）, acetylcholinesteras （Ache） activity in brain, vitamin E concentration, and reactive oxygen species （ROS） in serum were determined. The latency period （the time during which the mice swim from the starting position to the ending position） and errors （the number of mice entering the blind end） in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. Results The latency period as well as errors in the air, control diet, tobacco smoke （TS）, and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups （P〈O.05）. LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras （Ache） activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group （P〈0.05）. Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. Conclusion Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS （especially vitamin E） partially improve the learning and memory smoke during pregnancy. and Ache activity and increasing NO content. Antioxidants ability of offsprings whose mothers are exposed to tobacco

Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

Objective The potential of all central nervous system synapses to exhibit long term potentiation （LTP） or long term depression （LTD） is subject to modulation by prior synaptic activity, a higher-order form of plasticity that has been termed metaplasticity. This study is designed to examine the plasticity and metaplasticity in the lateral perforant path of rat. Methods Field potential was measured with different priming and conditioning stimulation protocols. Results Ten-hertz priming, which does not affect basal synaptic transmission, caused a dramatic reduction in subsequent LTP at lateral perforant path synapses in vitro, and the reduced LTP lasted for at least 2 h. The LTD was unaffected. The reduction of LTP in the lateral perforant path was also readily induced by applying priming antidromically at the mossy fibers. Conclusion Priming with 10 Hz, which is within a frequency range observed during physiological activity, can cause potent, long-lasting inhibition of LTP, but not LTD. This form of metaplasticity adds a layer of complexity to the activity-dependent modification of synapses within the dentate gyrus.

Ex Vivo Characterization of the Action of Sideritis Extract Using Electrical Activity in the Rat Hippocampus Slice Preparation

A hydroethanolic extract (20% V/V) from Herba Sideritis scardica has been recognized to positively influence cognition. The present investigation aimed at the question if this extract would be able to modify intra-hippocampal communication after oral administration of 100 mg/kg daily for one week. The glutamatergic synapse between Schaffer Collaterals and pyramidal cells can be tested by electric stimulation using single pulses or theta burst stimulation. The resulting population spike is modulated by compounds acting at the central nervous system or other preparations directly or as ex vivo approach. In this case the effect of the special extract was tested in vitro the next day after repetitive in vitro administration. Conventional recording technique in the in vitro hippocampus slice revealed an increase of the population spike in the presence of single stimuli and theta burst stimuli resulting in increased long-term potentiation. This effect was tried to modulate by several glutamate receptor antagonists, among them compounds targeting at the ionic NMDA receptor (CGS19755), AMPA receptor (NBQX), Kainate receptor (UBP301) and targeting at three metabotropic glutamate receptors (mGluR I (YM298198), mGluRII ((RS)-APICA)) and mGluRIII (MSOP). Only NBQX was able to prevent the action of the Sideritis scardica extract. Since the AMPA receptor has been related to cognition in several reports in the literature, it is concluded from this result that the positive action of Sideritis scardica extract on brain function involves a modulation of AMPA receptor dependent neurotransmission.

Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices:Multi-electrode array recordings

Objective There is substantial evidence supporting the notion that the anterior cingulate cortex （ACC） is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation （LTP） is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli （CS） protocols. Methods A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation （TBS） paradigms were applied in layer V-VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts （4 pulses at 100 Hz） with a 200 ms interval, however, the former （TBS1） was with 10 trains and the latter （TBS2） was with 5 trains. After test stimulation at layer V-VI in the ACC, network field potentials （FPs） could be simultaneously recorded across all layers of the ACC. Results The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V-VI, in contrast, complex waveforms were localized mainly in layers II-III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS 1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II-III and layers V-VI without layer-related difference. However, no LTP was inducible in layer I. Conclusion The present findings indicate that stimulation protocols may, at least in part, account for a large portion of variations among previous LTP studies, and hence highlight the importance of selecting the best LTP induction protocol when designing such experiments. Moreover, the present results demonstrate the prominent superiority of multi-electrode array recording in revealing the network properties of synaptic activities in the ACC, especially in comparing the spatiotemporal characteristics between different layers of this structure.