Effects of prolonged exposure to context following contextual fear conditioning on synaptic properties in rat hippocampal slices

Acute stressful events enhance plasma corticosterone release and profoundly affect synaptic functions, which are involved in the development of stress-related cognitive and mental disorders. However, how exposure to stressful context immediately after str

Stress and long-term synaptic depression

Acute inescapable stress reverses the direction of synaptic plasticity in the intact hippocampus via a corticosterone-mediated activation of glucocorticoid receptors and protein/RNA synthesis.

Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats, Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation, We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and longterm potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents, The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D, Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA, This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: Possible mechanisms for corticosterone on opiate addiction

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation ( similar to 20%) to synaptic depression ( similar to 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation ON was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber 13 (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD. (c) 2005 Wiley-Liss, Inc.

Propofol effects on excitatory synaptic efficacy in the CA1 region of the developing hippocarnpus

The anesthetic, propofol, effectively suppresses excitatory synaptic transmission and facilitates long-term depression (LTD) in the CA1 region of the hippocampus. Here, we have examined whether these effects are different in the developing hippocampus. We found that propofol in suppressing whole-cell excitatory postsynaptic currents (EPSC) was more effective in 21 day old rats than either in 7 day old rats or under the condition of high intracellular chloride concentration in 21 day old rats. Furthermore, the propofol concentration to facilitate the NMDA receptor-dependent LTD was lower at postnatal day 21 than at postnatal day 7. Interestingly, the decay time of EPSC was decreased during the development from postnatal day 7 to 21, but it was increased by the recording condition of high intracellular chloride concentration or by propofol administration. All these effects of propofol were dependent on the chloride channel opening. These observations suggest that propofol may induce differential anesthetic effects in the developing hippocampus, at least partially, depending on the intracellular chloride concentration. (c) 2005 Elsevier B.V. All rights reserved.

N-methyl-D-aspartate receptor-dependent long-term potentiation in CA1 region affects synaptic expression of glutamate receptor subunits and associated proteins in the whole hippocampus

Long term potentiation in hippocampus, evoked by high-frequency stimulation, is mediated by two major glutamate receptor subtypes, alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptors and N-methyl-D-aspartate receptors. Receptor subunit compos

Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring

Clinical studies demonstrate that prenatal stress causes cognitive deficits and increases vulnerability to affective disorders in children and adolescents. The underlying mechanisms are not yet fully understood. Here, we reported that prenatal stress (10

Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo

Subiculum receives output of hippocampal CAI neurons and projects glutamatergic synapses onto nucleus accumbens (NAc), the subicular-NAc pathway linking memory and reward system. It is unknown whether morphine withdrawal influences synaptic plasticity in

Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress

Prenatal stress can cause long-term effects on cognitive functions in offspring. Hippocampal synaptic plasticity, believed to be the mechanism underlying certain types of learning and memory, and known to be sensitive to behavioral stress, can be changed

Opioid Withdrawal for 4 Days Prevents Synaptic Depression Induced by Low Dose of Morphine or Naloxone in Rat Hippocampal CA1 Area In Vivo

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (C) 2009 Wiley-Liss, Inc.

The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats

1 It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used

Know thy neighbour: A normative theory of synaptic depression

Synapses exhibit an extraordinary degree of short-term malleability, with release probabilities and effective synaptic strengths changing markedly over multiple timescales. From the perspective of a fixed computational operation in a network, this seems like a most unacceptable degree of added variability. We suggest an alternative theory according to which short-term synaptic plasticity plays a normatively-justifiable role. This theory starts from the commonplace observation that the spiking of a neuron is an incomplete, digital, report of the analog quantity that contains all the critical information, namely its membrane potential. We suggest that a synapse solves the inverse problem of estimating the pre-synaptic membrane potential from the spikes it receives, acting as a recursive filter. We show that the dynamics of short-term synaptic depression closely resemble those required for optimal filtering, and that they indeed support high quality estimation. Under this account, the local postsynaptic potential and the level of synaptic resources track the (scaled) mean and variance of the estimated presynaptic membrane potential. We make experimentally testable predictions for how the statistics of subthreshold membrane potential fluctuations and the form of spiking non-linearity should be related to the properties of short-term plasticity in any particular cell type.

SynGAP isoforms exert opposing effects on synaptic strength.

Alternative promoter usage and alternative splicing enable diversification of the transcriptome. Here we demonstrate that the function of Synaptic GTPase-Activating Protein (SynGAP), a key synaptic protein, is determined by the combination of its amino-terminal sequence with its carboxy-terminal sequence. 5' rapid amplification of cDNA ends and primer extension show that different N-terminal protein sequences arise through alternative promoter usage that are regulated by synaptic activity and postnatal age. Heterogeneity in C-terminal protein sequence arises through alternative splicing. Overexpression of SynGAP α1 versus α2 C-termini-containing proteins in hippocampal neurons has opposing effects on synaptic strength, decreasing and increasing miniature excitatory synaptic currents amplitude/frequency, respectively. The magnitude of this C-terminal-dependent effect is modulated by the N-terminal peptide sequence. This is the first demonstration that activity-dependent alternative promoter usage can change the function of a synaptic protein at excitatory synapses. Furthermore, the direction and degree of synaptic modulation exerted by different protein isoforms from a single gene locus is dependent on the combination of differential promoter usage and alternative splicing.