Long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are forms of synaptic plasticity that have been studied extensively and are thought to contribute to learning and memory. The reversal of LTP, known as depotentiation (DP) has received far less attention however, and its role in behavior is also far from clear. Recently, deficits in depotentiation have been observed in models of schizophrenia, suggesting that a greater understanding of this form of synaptic plasticity may help reveal the physiological alterations that underlie symptoms experienced by patients. This review therefore seeks to summarize the current state of knowledge on DP, and then put the deficits in DP in models of disease into this context.
Depression ; Humans ; Learning ; Long-Term Potentiation ; Long-Term Synaptic Depression ; Memory ; Neuronal Plasticity ; Plastics ; Schizophrenia ; Synaptic Transmission

Aquaporin-4 (AQP-4) is the predominant water channel in the central nervous system (CNS) and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. However, the role of AQP-4 in regulating synaptic plasticity, learning and memory, cognitive function is only beginning to be investigated. It is well known that synaptic plasticity is the prime candidate for mediating of learning and memory. Long term potentiation (LTP) and long term depression (LTD) are two forms of synaptic plasticity, and they share some but not all the properties and mechanisms. Hippocampus is a part of limbic system that is particularly important in regulation of learning and memory. This article is to review some research progresses of the function of AQP-4 in synaptic plasticity, learning and memory, and propose the possible role of AQP-4 as a new target in the treatment of cognitive dysfunction.
Animals ; Aquaporin 4 ; physiology ; Hippocampus ; physiology ; Humans ; Learning ; Long-Term Potentiation ; Long-Term Synaptic Depression ; Memory ; Neuronal Plasticity

Animals ; Brain ; physiology ; Extinction, Psychological ; physiology ; Humans ; Long-Term Potentiation ; Long-Term Synaptic Depression ; Neural Pathways ; physiology ; Neuronal Plasticity ; Neurons ; physiology ; Receptors, AMPA ; physiology

Long-Term Potentiation ; Neuronal Plasticity ; Receptors, Metabotropic Glutamate ; Synaptic Transmission

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

BACKGROUNDTraumatic brain injury (TBI) often causes cognitive deficits and remote symptomatic epilepsy. Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBI may impair the cellular circuit in the hippocampus.

METHODSForty male Wistar rats were randomized into control (n = 20) and TBI groups (n = 20). Long-term potentiation, extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.

RESULTSTBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.

CONCLUSIONSTBI leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

Animals ; Brain Injuries ; physiopathology ; Hippocampus ; physiopathology ; Long-Term Potentiation ; Male ; Neuronal Plasticity ; physiology ; Rats ; Rats, Wistar

Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation.
Animals ; Compensation and Redress* ; Hippocampus* ; Long-Term Potentiation* ; Neuronal Plasticity ; Rats* ; Synapses*

Circadian rhythms are driven by circadian oscillators, and these rhythms result in the biological phenomenon of 24-h oscillations. Previous studies suggest that learning and memory are affected by circadian rhythms. One of the genes responsible for generating the circadian rhythm is Rev-erbα. The REV-ERBα protein is a nuclear receptor that acts as a transcriptional repressor, and is a core component of the circadian clock. However, the role of REV-ERBα in neurophysiological processes in the hippocampus has not been characterized yet. In this study, we examined the time-dependent role of REV-ERBα in hippocampal synaptic plasticity using Rev-erbα KO mice. The KO mice lacking REV-ERBα displayed abnormal NMDAR-dependent synaptic potentiation (E-LTP) at CT12~CT14 (subjective night) when compared to their wild-type littermates. However, Rev-erbα KO mice exhibited normal E-LTP at CT0~CT2 (subjective day). We also found that the Rev-erbα KO mice had intact late LTP (L-LTP) at both subjective day and night. Taken together, these results provide evidence that REV-ERBα is critical for hippocampal E-LTP during the dark period.
Animals ; Biological Phenomena ; Circadian Clocks ; Circadian Rhythm ; Hippocampus ; Learning ; Long-Term Potentiation ; Memory ; Mice ; Neuronal Plasticity

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3
Animals ; Hippocampus ; Long-Term Potentiation ; Mice ; Neuronal Plasticity ; Nuclear Receptor Coactivator 3/genetics* ; Synapses

Extracellular recordings of field excitatory postsynaptic potential (fEPSP) is one of the most common ways for studies of synaptic plasticity, such as long-term potentiation (LTP) and paired-pulse plasticity (PPP). The measurement of the changes in the different components of fEPSP waveform, such as the initial slope, initial area, peak amplitude and whole area, were commonly used as criteria for the judgement of potentiation or depression of synaptic plasticity. However, the differences in the conclusions drawn from measuring different components of fEPSP waveform at the same recording have still been largely ignored. Here we compared high-frequency stimulation (HFS)-evoked synaptic plasticity, both LTP and PPP, by measuring different components of fEPSP waveform, including the initial slope, initial area, peak amplitude, whole area and time course. The results not only indicated the acceleration of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor kinetics underlies LTP in hippocampal CA1 region of mice, but also showed that different measurements of fEPSP waveform at the same recording result in different magnitudes of LTP and different forms of PPP in hippocampal CA1 region of mice. After HFS, the paired-pulse ratio was slightly decreased by measurement of the initial area, but obviously increased by measurement of the initial slope of the pair fEPSPs. These results might draw apparently contradictory conclusions. Therefore, careful and complete analysis of the data from different parts of fEPSP waveforms is important for reflection of the faithful changes in synaptic plasticity.
Animals ; CA1 Region, Hippocampal ; physiology ; Excitatory Postsynaptic Potentials ; Long-Term Potentiation ; Mice ; Neuronal Plasticity ; Receptors, AMPA ; metabolism