Myelin degeneration is one of the characteristics of aging and degenerative diseases. This study investigated age-related alterations in expression of myelin basic protein (MBP) in the hippocampal subregions (dentate gyrus, CA2/3 and CA1 areas) of gerbils of various ages; young (1 month), adult (6 months) and aged (24 months), using western blot and immunohistochemistry. Western blot results showed tendencies of age-related reductions of MBP levels. MBP immunoreactivity was significantly decreased with age in synaptic sites of trisynaptic loops, perforant paths, mossy fibers, and Schaffer collaterals. In particular, MBP immunoreactive fibers in the dentate molecular cell layer (perforant path) was significantly reduced in adult and aged subjects. In addition, MBP immunoreactive mossy fibers in the dentate polymorphic layer and in the CA3 striatum radiatum was significantly decreased in the aged group. Furthermore, we observed similar age-related alterations in the CA1 stratum radiatum (Schaffer collaterals). However, the density of MBP immunoreactive fibers in the dentate granular cell layer and CA stratum pyramidale was decreased with aging. These findings indicate that expression of MBP is age-dependent and tissue specific according to hippocampal layers.
Adult* ; Aging ; Blotting, Western ; CA1 Region, Hippocampal ; Gerbillinae* ; Hippocampus* ; Humans ; Immunohistochemistry ; Myelin Basic Protein* ; Myelin Sheath* ; Perforant Pathway

Like neurons, astrocytes produce and release GABA to influence neuronal signaling. At the perforant path to dentate gyrus granule neuron synapse, GABA from astrocyte was found to be a strong inhibitory factor, which impairs synaptic transmission, synaptic plasticity and memory in Alzheimer's disease. Although astrocytic GABA is observed in many brain regions, its physiological role has not been clearly demonstrated yet. Here, we show that astrocytic GABA exerts disinhibitory action to dentate granule neurons by targeting GABA(B) receptors of GABAergic interneurons in wild-type mice. This disinhibitory effect is specific to a low intensity of electrical stimulation at perforant path fibers. Inversely in Alzheimer's disease model mice, astrocytic GABA targets GABA(A) receptors and exerts inhibitory action by reducing release probability of glutamatergic perforant path terminals. These results suggest that astrocytic GABA differentially modulates the signaling from cortical input to dentate gyrus under physiological and pathological conditions.
Alzheimer Disease* ; Animals ; Astrocytes ; Brain ; Dentate Gyrus* ; Electric Stimulation ; gamma-Aminobutyric Acid* ; Interneurons ; Memory ; Mice ; Neurons* ; Perforant Pathway* ; Plastics ; Receptors, GABA-A ; Synapses* ; Synaptic Transmission

Febrile seizure (FS) is common in childhood and can impair cognitive function. The potential to exhibit plasticity at many synapses appears to be modulated by prior synaptic activity. This intriguing higher-order form of plasticity has been termed metaplasticity. Plasticity and metaplasticity have been considered to be one of the most important neurological fundaments of learning and memory. In the present study, field potential recording was carried out to detect the effects of FS on plasticity and metaplasticity in the lateral perforant path of rat hippocampus. Brain slices from rat pups of FS model were prepared and superfused. The recording electrodes were placed within the outer molecular layer for recording of lateral perforant path field excitatory postsynaptic potentials (fEPSP). Stimulation of the lateral perforant path and the dentate hilar region was carried out by placing bipolar stimulating electrodes within the outer molecular layer and hilus, respectively. The results showed that long term potentiation (LTP) of control and FS rats didn't show significant difference after 100 Hz conditioning stimulation. Subjected to 10 Hz priming stimulation applied to lateral perforant path or dentate hilar region 40 min prior to 100 Hz conditioning, the LTP of control group was inhibited, while the LTP of FS rats remained constant. Normalized fEPSP slope 1 h after tetanization of control group was 1.10 ± 0.26 and 1.15 ± 0.14 after homosynaptic and antidromic priming stimulation respectively. On the contrast, FS group didn't show any depression of LTP after homosynaptic and antidromic priming stimulation, normalized fEPSP slope 1 h after tetanization being 1.35 ± 0.2 and 1.47 ± 0.19, respectively. These results suggest that FS would impair lateral perforant path metaplasticity without affecting LTP. These findings represent an intriguing phenomenon of FS-caused brain damage and imply the injury of excitatory status in different pathways.
Animals ; Animals, Newborn ; Dentate Gyrus ; physiopathology ; Excitatory Postsynaptic Potentials ; physiology ; Male ; Neuronal Plasticity ; physiology ; Perforant Pathway ; cytology ; Rats ; Rats, Sprague-Dawley ; Seizures, Febrile ; physiopathology ; Synapses ; physiology

OBJECTIVE: Although, accumulating evidence is delineating a neuroprotective and neurotrophic role for lithium (Li), inconsistent findings have also been reported in human studies especially. Moreover, the effects of Li infusion into the hippocampus are still unknown. The aims of this work were (a) to assess whether basal synaptic activity and long-term potentiation (LTP) in the hippocampus are different in regard to intrahippocampal Li infusion; (b) to assess spatial learning and memory in rats chronically treated with LiCO₃ in the Morris water maze. METHODS: Field potentials were recorded form the dentate gyrus, stimulating perforant pathways, in rats chronically (20 mg/kg for 40 days) or acutely treated with LiCO₃ and their corresponding control rats. In addition, performance of rats in a Morris water maze was measured to link behaviour of rats to electrophysiological findings. RESULTS: LiCO₃ infusion into the hippocampus resulted in enhanced LTP, especially in the late phases, but attenuated LTP was observed in rats chronically treated with Li as compared to controls. Li-treated rats equally performed a spatial learning task, but did spend less time in target quadrant than saline-treated rats in Morris water maze. CONCLUSION: Despite most data suggest that Li always yields neuroprotective effects against neuropathological conditions; we concluded that a 40-day treatment of Li disrupts hippocampal synaptic plasticity underlying memory processes, and that these effects of prolonged treatment are not associated with its direct chemical effect, but are likely to be associated with the molecular actions of Li at genetic levels, because its short-term effect preserves synaptic plasticity.
Adult ; Animals ; Dentate Gyrus ; Hippocampus ; Humans ; Learning ; Lithium ; Long-Term Potentiation ; Memory ; Neuronal Plasticity ; Neuroprotective Agents ; Perforant Pathway ; Rats ; Spatial Learning ; Spatial Memory ; Water

Translationally controlled tumor protein (TCTP) is a cytosolic protein with microtubule stabilization and calcium-binding activities. TCTP is expressed in most organs including the nervous system. However, detailed distribution and functional significance of TCTP in the brain remain unexplored. In this study, we investigated the global and subcellular distributions of TCTP in the mouse brain. Immunohistochemical analyses with anti-TCTP revealed that TCTP was widely distributed in almost all regions of the brain including the cerebral cortex, thalamus, hypothalamus, hippocampus, and amygdala, wherein it was localized in axon tracts and axon terminals. In the hippocampus, TCTP was prominently localized to axon terminals of the perforant path in the dentate gyrus, the mossy fibers in the cornu ammonis (CA)3 region, and the Schaffer collaterals in the CA1 field, but not in cell bodies of granule cells and pyramidal neurons, and in their dendritic processes. Widespread distribution of TCTP in axon tracts and axon terminals throughout the brain suggests that TCTP is likely involved in neurotransmitter release and/or maintaining synaptic structures in the brain, and that it might have a role in maintaining synaptic functions and synaptic configurations important for normal cognitive, stress and emotional functions.
Amygdala ; Animals ; Axons* ; Brain ; Cell Body ; Cerebral Cortex ; Cognition ; Cytosol ; Dentate Gyrus ; Hippocampus ; Hypothalamus ; Immunohistochemistry ; Mice* ; Microtubules ; Nervous System ; Neurons* ; Neurotransmitter Agents ; Perforant Pathway ; Presynaptic Terminals* ; Pyramidal Cells ; Thalamus

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.
Animals ; Animals, Newborn ; Dentate Gyrus ; drug effects ; Excitatory Postsynaptic Potentials ; Fatty Acids, Omega-3 ; pharmacology ; Fish Oils ; chemistry ; Lead Poisoning ; physiopathology ; Long-Term Potentiation ; drug effects ; Perforant Pathway ; Rats ; Rats, Wistar

AIMTo study the effect of ZD7288 on synaptic transmission in the pathway from perforant pathway (PP) fibers to CA3 region in rat hippocampus.

METHODSThe extracellular recording technique in vivo was used to record the CA3 region field potentials. High-performance liquid chromatography (HPLC) with fluorescence detection was applied to measure the content of amino acids in hippocampal tissues. The effect of ZD7288 and CsCl on the amplitudes of population spike (PS) in CA3 region evoked by stimulation (0.5 Hz) of the perforant pathway (PP) fibers, and the content of amino acids in hippocampal tissue were observed.

RESULTSMicroinjection of ZD7288 (20, 100 and 200 nmol) and CsCl (1, 5 and 10 micromol) into CA3 region decreased the population spike (PS) amplitudes in a dose-dependent manner. The inhibitory effects appeared at 5 min after microinjection and lasted at least 90 min. In those rats treated with ZD7288 (100 nmol), the contents of glutamate, aspartate, glycine and GABA decreased significantly as compared to those of saline control (all P < 0.01, except P < 0.05 for that of glycine). A similar decrease in the contents of amino acids was observed when the rats were microinjected with CsCl (5 micromol). CONCLUSION; ZD7288 could obviously inhibit synaptic transmission in the pathway from PP fibers to CA3 region in rat hippocampus, and this action of ZD7288 may be associated with altered contents of amino acids.

Amino Acids ; metabolism ; Animals ; Cesium ; pharmacology ; Chlorides ; pharmacology ; Dose-Response Relationship, Drug ; Evoked Potentials ; Hippocampus ; metabolism ; physiology ; Male ; Microinjections ; Perforant Pathway ; physiology ; Pyrimidines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission ; drug effects

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

AIMTo investigate the influence of platelet-activating factor (PAF) receptor on long-term potentiation (LTP) attenuated by aluminium.

METHODSThe method of extracellular recording was used to investigate the effect of PAF receptors on PP-CA3 LTP by microinjection of PAF receptor antagonist Ginkgolide B or agonist mc-PAF into CA3 area.

RESULTS(1) Amplitude of population spikes (PS) of evoked potential was not affected but LTP induction was blocked by 0.2 micromol/L ginkgolide B in CA3 area. (2) LTP induction was not influenced by 0.25 mol/L aluminium chloride, however, it could be blocked when aluminium was applicated with ginkgolide B. (3) LTP induction was influenced slightly by 40 micromol/L mc-PAF but it has no difference in statistic. LTP induction could be blocked completely by 0.5 mol/L aluminium, but when aluminium was coapplicated with mc-PAF, this effect could be relieved.

CONCLUSIONThese results indicate that PAF receptors are involved in induction of LTP in CA3 area by stimulating perforant path. The inhibitory effect of aluminium on LTP is partly related to PAF receptors.

Aluminum Compounds ; toxicity ; Animals ; CA3 Region, Hippocampal ; drug effects ; metabolism ; Electric Stimulation ; Evoked Potentials ; drug effects ; Ginkgolides ; pharmacology ; Lactones ; pharmacology ; Long-Term Potentiation ; drug effects ; Perforant Pathway ; Platelet Membrane Glycoproteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is widely considered as one of the major mechanisms underlying learning and memory. This study explored hippocampal synaptic plasticity and spatial memory formation of an Alzheimer's disease (AD) rat model established by intrahippocampal injection of oligomeric Aβ(1-42). Twenty four Sprague-Dawley rats at 2.5 months of age were randomly divided into AD and control groups, and were bilaterally injected with 5 μg oligomeric Aβ(1-42) or normal saline into dentate gyrus (DG) of hippocampus. Morris water maze test was used to observe the capability of learning and memory of two groups, 30 d after injection. To investigate the variations of paired-pulse facilitation (PPF) and range of synaptic plasticity, field potentials were recorded in the DG of the dorsal hippocampus by stimulating the perforant path (PP). The results showed that oligomeric Aβ(1-42) obviously impaired spatial memory formation in rats (P < 0.05). Furthermore, oligomeric Aβ(1-42) reduced the PPF ratio (P < 0.05) and hippocampal LTP formation (P < 0.05), while facilitated the hippocampal LTD formation (P < 0.05). These data suggest that chronic Aβ aggregation impairs synaptic plasticity of hippocampal PP-DG pathway, which may be involved in the spatial memory deficit in AD rats.
Alzheimer Disease ; chemically induced ; physiopathology ; Amyloid beta-Peptides ; toxicity ; Animals ; Female ; Hippocampus ; physiopathology ; Long-Term Potentiation ; drug effects ; physiology ; Long-Term Synaptic Depression ; drug effects ; physiology ; Male ; Maze Learning ; Memory ; physiology ; Neuronal Plasticity ; drug effects ; physiology ; Oligopeptides ; toxicity ; Peptide Fragments ; toxicity ; Perforant Pathway ; physiology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; physiology