Deep brain stimulation (DBS), which usually utilizes high frequency stimulation (HFS) of electrical pulses, is effective for treating many brain disorders in clinic. Studying the dynamic response of downstream neurons to HFS and its time relationship with stimulus pulses can reveal important mechanisms of DBS and advance the development of new stimulation modes (e.g., closed-loop DBS). To exhibit the dynamic neuronal firing and its relationship with stimuli, we designed a two-dimensional raster plot to visualize neuronal activity during HFS (especially in the initial stage of HFS). Additionally, the influence of plot resolution on the visualization effect was investigated. The method was then validated by investigating the neuronal responses to the axonal HFS in the hippocampal CA1 region of rats. Results show that the new design of raster plot is able to illustrate the dynamics of indexes (such as phase-locked relationship and latency) of single unit activity (i.e., spikes) during periodic pulse stimulations. Furthermore, the plots can intuitively show changes of neuronal firing from the baseline before stimulation to the onset dynamics during stimulation, as well as other information including the silent period of spikes immediately following the end of HFS. In addition, by adjusting resolution, the raster plot can be adapted to a large range of firing rates for clear illustration of neuronal activity. The new raster plot can illustrate more information with a clearer image than a regular raster plot, and thereby provides a useful tool for studying neuronal behaviors during high-frequency stimulations in brain.
Action Potentials ; Animals ; Axons ; physiology ; CA1 Region, Hippocampal ; physiology ; Deep Brain Stimulation ; Neurons ; physiology ; Rats

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.
Aging ; Animals ; CA1 Region, Hippocampal ; physiology ; Cognition ; drug effects ; Inflammasomes ; metabolism ; Long-Term Potentiation ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Panax ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

The aim of this study was to investigate whether G protein-coupled estrogen receptor (GPER) could alleviate hippocampal neuron injury under cerebral ischemia-reperfusion injury (CIRI) by acting on endoplasmic reticulum stress (ERS). The CIRI animal model was established by middle cerebral artery occlusion (MCAO). Female ovariectomized (OVX) Sprague-Dawley (SD) female rats were randomly divided into 4 groups: control, ischemia-reperfusion injury (MCAO), vehicle (MCAO+DMSO), and GPER-specific agonist G1 (MCAO+G1) groups. The neurobehavioral score was assessed by the Longa score method, the morphological changes of the neurons were observed by the Nissl staining, the cerebral infarction was detected by the TTC staining, and the neural apoptosis in the hippocampal CA1 region was detected by TUNEL staining. The distribution and expression of GRP78 (78 kDa glucose-regulated protein 78) in the hippocampal CA1 region were observed by immunofluorescent staining. The protein expression levels of GRP78, Caspase-12, CHOP and Caspase-3 were detected by Western blot, and the mRNA expression levels of GRP78, Caspase-12, and CHOP were detected by the real-time PCR. The results showed that the neurobehavioral score, cerebral infarct volume, cellular apoptosis index, as well as GRP78, Caspase-12 and CHOP protein and mRNA expression levels in the MCAO group were significantly higher than those of control group. And G1 reversed the above-mentioned changes in the MCAO+G1 group. These results suggest that the activation of GPER can decrease the apoptosis of hippocampal neurons and relieve CIRI, and its mechanism may involve the inhibition of ERS.
Animals ; Apoptosis ; Brain Ischemia ; CA1 Region, Hippocampal ; cytology ; Caspase 12 ; metabolism ; Caspase 3 ; metabolism ; Endoplasmic Reticulum Stress ; Female ; Heat-Shock Proteins ; metabolism ; Neurons ; cytology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; physiology ; Receptors, G-Protein-Coupled ; agonists ; Reperfusion Injury ; Transcription Factor CHOP ; metabolism

OBJECTIVETo investigate the effects of beta-amyloid (Aβ) and apolipoprotein E4(apoE4) on choline acetyl transferase (ChAT) in hippocampus and to explore possible the synergistic effect of both Aβ and apoE4.

METHODSMale Wistar rats were divided into four groups: control group, Aβ group, apoE4 group and Aβ + apoE4 group. Rats in different group received injection of normal saline, Aβ1-40, apoE4 and Aβ1-40 + apoE4, respectively, into bilateral hippocampus CA1 regions under the control of a brain stereotaxic apparatus. The learning-memory ability with the escape latency and the times of passing platform and the expression of ChAT in hippocampus CA1 regions were documented.

RESULTSThe escape latency at fifth day and the times of passing platform and ChAT mRNA PU values were obtained for the control group (10.75 s ± 2.44 s, 4.13 ± 0.64, and 28.90 ± 4.43), apoE4 group (23.88 s ± 4.32 s, 2.38 ± 0.52, and 20.85 ± 3.98), Aβ group (43.50 s ± 9.78 s, 1.38 ± 0.52, and 16.96 ± 2.53), and Aβ + apoE4 group (70.63 s ± 10.04 s, 0.75 ± 0.71, and 13.01 ± 2.21). Through 5 days of training all animals acquired learning-memory ability with the gradually shortened escape latency, although injection of Aβ1-40 and apoE4 all induced learning-memory damage, due to a significantly prolonged the escape latency at fifth day (P < 0.01) and markedly decreased the times of passing platform (P < 0.01) in both Aβ and apoE4 group than in control group. An interaction between Aβ and apoE4 also was observed, with further prolonged escape latency(P < 0.01). ChAT mRNA PU values were significantly lower in the Aβ group and apoE4 group than in the control group (P < 0.01). Aβ and apoE4 demonstrated interaction in lowering ChAT mRNA level(P < 0.05).

CONCLUSIONSBoth Aβ and apoE4 induce an injury to hippocampal cholinergic system and its learning-memory ability, in which Aβ and apoE4 have a synergistic effect in the initiation of such injury.

Alzheimer Disease ; enzymology ; physiopathology ; Amyloid beta-Peptides ; toxicity ; Animals ; Apolipoprotein E4 ; toxicity ; CA1 Region, Hippocampal ; enzymology ; physiology ; Choline O-Acetyltransferase ; genetics ; metabolism ; Drug Synergism ; Escape Reaction ; drug effects ; Learning ; drug effects ; Male ; Memory ; drug effects ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVEIn order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed.

METHODSRat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis.

RESULTS(1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending to be inhibitory connection between neurons in irradiation group after electromagnetic radiation.

CONCLUSIONElectromagnetic radiation may cause structure and function changes of transfer synaptic in global, make hippocampal CA1 area neurons change in the overall discharge characteristic and discharge patterns, thus lead to decrease in the ability of learning and memory.

Animals ; CA1 Region, Hippocampal ; cytology ; radiation effects ; Electromagnetic Radiation ; Male ; Neurons ; physiology ; radiation effects ; Rats ; Rats, Wistar

OBJECTIVETo determine 5-lipoxygenase (5-LOX) expression and the effect of zileuton, a selective 5-LOX inhibitor,on hippocampal neuron injury induced by global cerebral ischemia in rats.

METHODSGlobal cerebral ischemia was induced by bilateral common carotid artery occlusion combined with hypotension in rats. 5-LOX expression was detected by Western blot analyses and 5-LOX localization was visualized by immunohistochemistry and double immunofluorescence methods. The 5-LOX inhibitor zileuton (10, 30, 50 mg/kg) was orally administered for 3 d after ischemia.

RESULTSThe 5-LOX expression was increased in the ischemic hippocampus on d1-7 (peaked at d3), and 5-LOX protein was primarily localized in neurons and translocated to the nuclei in the hippocampal CA1 region after ischemia. The 5-LOX inhibitor zileuton (30, 50 mg/kg) reduced ischemia-induced hippocampal neurons death 3d after ischemia.

CONCLUSION5-LOX is involved in global cerebral ischemic damage in rats, and the 5-LOX inhibitor zileuton has a protective effect on neuronal damage in the rat hippocampus following global cerebral ischemia.

Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; physiology ; Brain Ischemia ; metabolism ; pathology ; CA1 Region, Hippocampal ; metabolism ; pathology ; Disease Models, Animal ; Hydroxyurea ; analogs & derivatives ; pharmacology ; Lipoxygenase Inhibitors ; pharmacology ; Male ; Neurons ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley

The purpose of this research is to investigate the critical period of voltage-gated Na(+) channel development in hippocampal CA1 neurons. Changes of Na(+) currents in acutely isolated hippocampal CA1 neurons of rats at different ages (0-4 weeks after birth) were recorded using the whole-cell patch-clamp technique. The results indicated that the maximum current density of Na(+) channels was increasing with age, and the amplitudes in 1, 2, 3 and 4 weeks respectively grew by (42.76 ± 4.91)%, (146.80 ± 7.63)%, (208.79 ± 5.28)% and (253.72 ± 5.74)% (n = 10, P < 0.05) compared with that in 0 week. The current density in CA1 neurons of 1-2 weeks after birth increased more significantly than those of other groups. The activation curve of Na(+) channel shifted to the left. The half-activation voltages (mV) in 0-2 weeks were -39.06 ± 0.65, -43.41 ± 0.52, -48.29 ± 0.45 (n = 10, P < 0.05), respectively, showing significant age-dependent decrease, and there were no significant changes in other groups. The slope factors of activation curve for each group did not change significantly. There were no regular changes in inactivation curve and no significant changes in half-inactivation voltage. The slope factors of inactivation curve in 1-2 weeks were: 5.77 ± 0.56, 4.42 ± 0.43 (n = 10, P < 0.05). The inactivation rate of the second week after birth was faster than that of the first week, and there were no significant changes during 0-1 week and 2-4 weeks. The recovery from inactivation curve of Na(+) channel shifted to the left. The recovery time declined in 1-3 weeks. Changes of action potential properties were consistent with Na(+) current. These results suggest that the period of 1-2 weeks after birth may be the critical development period of voltage-gated Na(+) channel in hippocampal CA1 neurons. During this time, the distribution of Na(+) channel increases significantly; the activation curve of Na(+) channel shifts to the left; inactivation rate increases as well as recovery time shortens.
Action Potentials ; Animals ; CA1 Region, Hippocampal ; cytology ; Neurons ; physiology ; Patch-Clamp Techniques ; Rats ; Sodium Channels ; physiology

Brain growth spurt (BGS) is the critical period of neuronal growth and synaptic connection. The voltage-gated K(+) channel is the key channel for maintenance of cell excitability and information transfer among neurons. The purpose of the present study is to investigate the critical period of voltage-gated K(+) channel development in hippocampal CA1 neurons during the BGS. Changes of voltage-gated K(+) currents in neurons from acutely isolated hippocampal CA1 brain slices of rats at different ages (0-4 weeks after birth) were recorded by the whole-cell patch-clamp technique. The depolarization voltage was set at +90 mV, and 0 week was set as the control group. The experimental results showed that, with increasing ages (1-4 weeks), the maximum current densities of IA increased by (16.14 ± 0.51)%, (81.73 ± 10.71)%, (106.72 ± 5.29)%, (134.58 ± 8.81)% (n = 10, P < 0.05), and the maximum current densities of IK increased by (16.75 ± 3.88)%, (134.01 ± 2.85)%, (180.56 ± 8.49)%, (194.5 ± 8.53)% (n = 10, P < 0.05), respectively, compared with those in 0 week. During 0-4 weeks after birth, the activation kinetics of IA shifted to left, and the half activation voltages of IA were 14.67 ± 0.75, 13.46 ± 0.64, 8.39 ± 0.87, 4.60 ± 0.96, 0.54 ± 0.92 (mV, n = 10, P < 0.05), respectively; The activation kinetics of IK shifted to left and the half activation voltages of IK were 8.94 ± 0.85, 6.65 ± 0.89, 0.47 ± 1.15, -1.80 ± 0.89, -8.56 ± 1.08 (mV, n = 10, P < 0.05) respectively. The inactivation kinetics of IA also shifted to left, and the half inactivation voltages were -45.68 ± 1.26, -46.81 ± 0.78, -48.64 ± 0.81, -51.96 ± 1.02, -58.31 ± 1.35 (mV, n = 10) respectively at 0, 1, 2, 3 and 4 weeks after birth, which showed no significant changes between 0 and 1 week, but significant decreases during 1-4 weeks after birth (P < 0.05). These results indicate that the current densities of IA and IK increase and the kinetic characteristics of the voltage-gated K(+) channels change with increasing ages during 0-4 weeks after birth, and the differences are especially significant between the 1st week and the 2nd week after birth. These changes may be related to the maturation of hippocampal neurons and the progress of their functions.
Animals ; CA1 Region, Hippocampal ; cytology ; Membrane Potentials ; Neurons ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; physiology ; Rats

OBJECTIVETo explore the effects of brain-derived neurotrophic factor (BDNF) pretreatment on beta amyloid protein (Abeta) induced impairment of in vivo hippocampal long-term potentiation (LTP) in the CA1 region of rats.

METHODSThirty-six adult male SD rats were randomly divided into six groups (n = 6): control, Abeta25-35, BDNF, (0.02 microg, 0.1 microg, 0.5 microg) BDNF + Abeta25-35. A self-made hippocampal local drug delivery catheter and a parallel bound stimulating/recording electrode were used to deliver drugs/stimulation and record field excitatory post-synaptic potentials (fEPSPs) in the hippocampal CA1 region of rats. High-frequency stimulation (HFS) was used to induce in vivo LTP.

RESULTS(1) Abeta25-35 (2 nmol) injection into CA1 region of rats did not affect the baseline fEPSPs, but inhibited the HFS-induced LTP significantly (P < 0.01). (2) Hippocampal CA1 injection of BDNF (0.1 microg) alone did not affect the baseline fEPSPs and HFS-induced LTP. (3) Compared with Abeta25-35 alone group, the averaged amplitude of LTP in BDNF (0.1 microg and 0.5 microg) plus Abeta25-35 groups significantly increased at 0 min, 30 min, and 60 min after HFS (P < 0.01), indicating that pretreatment with BDNF effectively protected against the Abeta,25-35 induced depression of LTP in a dose-dependent manner.

CONCLUSIONIntrahippocampal injection of BDNF can protect against the Abeta25-35-induced LTP impairment, suggesting that the up-regulation of BDNF in the brain could maintain the normal hippocampal synaptic plasticity and may contribute to the improvement of learning and memory in Alzheimer's (AD) disease patients.

Amyloid beta-Peptides ; antagonists & inhibitors ; Animals ; Brain-Derived Neurotrophic Factor ; pharmacology ; CA1 Region, Hippocampal ; drug effects ; physiology ; Excitatory Postsynaptic Potentials ; physiology ; Long-Term Potentiation ; physiology ; Male ; Peptide Fragments ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley

Using 64-channels (8 × 8) multi-electrode array technique (MED-64 system), the modulatory actions of 5-hydroxytryptamine (5-HT) 2C receptor subtype on the entorhinal (EC)-hippocampal synaptic transmission and connections were studied. One of freshly dissociated acute hippocampal slices of rats which was placed on the MED-64 probe, was subject to constant perfusion with oxygenated artificial cerebrospinal fluid (ACSF, 95% O2 and 5% CO2). Two hours after ACSF incubation, simultaneous multi-site electrophysiological recordings were performed. One electrode was selected to be used for perforant path (PP) stimulation, and the remaining 63 electrodes were used for recordings of network field excitatory postsynaptic potentials (fEPSPs) within both CA1 and dentate gyrus (DG) that have been previously proved to be mediated by glutamate non-NMDA receptors. After stability of network fEPSPs was achieved, (±)-1(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, an agonist of 5-HT2C receptor subtype), or SB242084 (6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride hydrate) (a selective antagonist of 5-HT2C receptor subtype) was applied for 10 min perfusion, respectively. Two-dimensional current source density (2D-CSD) analysis was also transformed by bilinear interpolation at each point of the 64 electrodes for spatial imaging of the fEPSP network responses. Based upon the polarities of fEPSP and 2D-CSD imaging, it was clearly shown that synaptic activations were evoked to occur within the molecular layer of DG and pyramidal cell layer of CA1 by the PP stimulation in which negative-going field potentials and current sink (blue) could be recorded. While, positive-going field potentials and current source (yellow) were mainly localized within the granule cell layer and hilus of DG and alveus of CA1, reflecting spread of electrical signals derived from depolarized region toward CA3 area or subiculum and fimbria along the axons. Perfusion of the hippocampal slices with DOI resulted in a significant enlargement of synaptic connection size at network level and enhancement of synaptic efficacy. However, on the contrary, perfusion with SB242084 produced reversal effect with either reduction in synaptic network size or decreased magnitude of fEPSPs (amplitude and slope) in the CA1 and DG. These results suggest that endogenous 5-HT causes facilitation of EC-CA1 and EC-DG synaptic transmission and connections via acting on 5-HT2C receptor subtype, leading to gain in synaptic transmission and enlargement of synaptic connections.
Animals ; CA1 Region, Hippocampal ; physiology ; Dentate Gyrus ; physiology ; Electrodes ; Entorhinal Cortex ; physiology ; Excitatory Postsynaptic Potentials ; Perforant Pathway ; Pyramidal Cells ; physiology ; Rats ; Receptor, Serotonin, 5-HT2C ; physiology ; Receptors, Glutamate ; physiology ; Serotonin ; physiology ; Synaptic Transmission