scholarly journals Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1306 ◽  
Author(s):  
Lindsey Friend ◽  
Ryan Williamson ◽  
Collin Merrill ◽  
Scott Newton ◽  
Michael Christensen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Biosynthetic Enzymes ◽  
Type I ◽  
Rt Pcr ◽  
Cellular Expression ◽  
Stratum Oriens ◽  
Term Potentiation

The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.

scholarly journals Mechanisms of heterosynaptic metaplasticity

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130148 ◽  
Author(s):  
Sarah R. Hulme ◽  
Owen D. Jones ◽  
Clarke R. Raymond ◽  
Pankaj Sah ◽  
Wickliffe C. Abraham
Keyword(s):  
Synaptic Plasticity ◽  
Long Range ◽  
Intercellular Communication ◽  
Atp Hydrolysis ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Signalling Pathways ◽  
Stratum Oriens ◽  
Term Potentiation

Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed ‘metaplasticity’, which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intra cellular versus inter cellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.

scholarly journals Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene

2021 ◽  
Author(s):  
Manuel F López-Aranda ◽  
Gayle M Boxx ◽  
Miranda Phan ◽  
Karen Bach ◽  
Rochelle Mandanas ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Long Term Potentiation ◽  
Null Mutation ◽  
Type I ◽  
Place Recognition ◽  
Interferon Signaling ◽  
Male Mice ◽  
Term Potentiation

Tuberous Sclerosis Complex (TSC) is a genetic disorder associated with high rates of intellectual disability and autism. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of TSC, the results presented here demonstrate a role for microglia in these deficits. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-), show deficits in hippocampal dependent tasks, as well as abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Here, we show that microglia and type I interferon signaling (IFN1) have a key role in the object place recognition (OPR; a hippocampal dependent task) deficits and abnormal LTP of Tsc2+/- male mice. Unexpectedly, we demonstrate that male, but not female, Tsc2+/- mice showed OPR deficits. Importantly, these deficits can be rescued by depletion of microglia, as well as by a genetic manipulation of a signaling pathway known to modulate microglia function (interferon-alpha/beta receptor alpha chain null mutation). In addition to rescuing the OPR deficits, depletion of microglia also reversed the abnormal LTP of the Tsc2+/- mice. Altogether, our results suggest that altered IFN1 signaling in microglia cause the abnormal LTP and OPR deficits of male Tsc2+/- mice.

scholarly journals Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 773-786 ◽  
Author(s):  
R. G. M. Morris ◽  
E. I. Moser ◽  
G. Riedel ◽  
S. J. Martin ◽  
J. Sandin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Cellular Mechanisms ◽  
Memory Processing ◽  
Functional Studies ◽  
Term Potentiation ◽  
Intermediate Storage ◽  
Activity Dependent

The hypothesis that synaptic plasticity is a critical component of the neural mechanisms underlying learning and memory is now widely accepted. In this article, we begin by outlining four criteria for evaluating the ‘synaptic plasticity and memory (SPM)’ hypothesis. We then attempt to lay the foundations for a specific neurobiological theory of hippocampal (HPC) function in which activity-dependent synaptic plasticity, such as long-term potentiation (LTP), plays a key part in the forms of memory mediated by this brain structure. HPC memory can, like other forms of memory, be divided into four processes: encoding, storage, consolidation and retrieval. We argue that synaptic plasticity is critical for the encoding and intermediate storage of memory traces that are automatically recorded in the hippocampus. These traces decay, but are sometimes retained by a process of cellular consolidation. However, we also argue that HPC synaptic plasticity is not involved in memory retrieval, and is unlikely to be involved in systems-level consolidation that depends on HPC-neocortical interactions, although neocortical synaptic plasticity does play a part. The information that has emerged from the worldwide focus on the mechanisms of induction and expression of plasticity at individual synapses has been very valuable in functional studies. Progress towards a comprehensive understanding of memory processing will also depend on the analysis of these synaptic changes within the context of a wider range of systems-level and cellular mechanisms of neuronal transmission and plasticity.

scholarly journals Evidence for reduced long-term potentiation-like visual cortical plasticity in schizophrenia and bipolar disorder

2020 ◽  
Author(s):  
Mathias Valstad ◽  
Daniël Roelfs ◽  
Nora B. Slapø ◽  
Clara M.F. Timpe ◽  
Ahsan Rai ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Synaptic Plasticity ◽  
Symptom Severity ◽  
Cortical Plasticity ◽  
Long Term Potentiation ◽  
Type I ◽  
Term Potentiation ◽  
Spectrum Disorders ◽  
Visual Cortical

AbstractBackgroundSeveral lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication.MethodsWe measured the VEP of patients with SZ spectrum disorders (n=31), BDI (n=34), BDII (n=33), and other BD spectrum disorders (n=2), and age-matched healthy control participants (n=200) before and after prolonged visual stimulation.ResultsCompared to healthy controls, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ2=35.1, p=3.1×10−9) and BD spectrum (χ2=7.0, p=8.2×10−3), including BDI (χ2=6.4, p=0.012), but not BDII (χ2=2.2, p=0.14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ2=14.2, p=1.7×10−4). The reduction in N1b modulation was related to PANSS total scores (χ2=10.8, p=1.0×10−3), and nominally to number of psychotic episodes (χ2=4.9, p=0.027). Conclusions. These results suggest that LTP-like plasticity is impaired in SZ and BDI, but not BDII, and related to psychotic symptom severity. Adding to previous genetic, pharmacological, and anatomical evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

scholarly journals Staufen1 Regulation of Protein Synthesis-Dependent Long-Term Potentiation and Synaptic Function in Hippocampal Pyramidal Cells

2008 ◽  
Vol 28 (9) ◽  
pp. 2896-2907 ◽  
Author(s):  
Geneviève Lebeau ◽  
Marjolaine Maher-Laporte ◽  
Lisa Topolnik ◽  
Charles E. Laurent ◽  
Wayne Sossin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Translational Control ◽  
Rna Binding ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Down Regulation ◽  
Spine Shape ◽  
Term Potentiation

ABSTRACT Staufen1 (Stau1) is an RNA-binding protein involved in transport, localization, decay, and translational control of mRNA. In neurons, it is present in cell bodies and also in RNA granules which are transported along dendrites. Dendritic mRNA localization might be involved in long-term synaptic plasticity and memory. To determine the role of Stau1 in synaptic function, we examined the effects of Stau1 down-regulation in hippocampal slice cultures using small interfering RNA (siRNA). Biolistic transfection of Stau1 siRNA resulted in selective down-regulation of Stau1 in slice cultures. Consistent with a role of Stau1 in transporting mRNAs required for synaptic plasticity, Stau1 down-regulation impaired the late form of chemically induced long-term potentiation (L-LTP) without affecting early-LTP, mGluR1/5-mediated long-term depression, or basal evoked synaptic transmission. Stau1 down-regulation decreased the amplitude and frequency of miniature excitatory postsynaptic currents, suggesting a role in maintaining efficacy at hippocampal synapses. At the cellular level, Stau1 down-regulation shifted spine shape from regular to elongated spines, without changes in spine density. The change in spine shape could be rescued by an RNA interference-resistant Stau1 isoform. Therefore, Stau1 is important for processing and/or transporting in dendrites mRNAs that are critical in regulation of synaptic strength and maintenance of functional connectivity changes underlying hippocampus-dependent learning and memory.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

scholarly journals Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

2021 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Chondroitin Sulphate ◽  
Memory Loss ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

Prenatal stress in rats attenuates hippocampal long-term potentiation and induces deficits in synaptic plasticity

2006 ◽  
Vol 16 ◽  
pp. S52
Author(s):  
S. Salomon ◽  
Y. Nachum-Biala ◽  
Y. Bogush ◽  
M. Lineal ◽  
H. Matzner ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Prenatal Stress ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Synaptic plasticity-dependent competition rule influences memory formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yire Jeong ◽  
Hye-Yeon Cho ◽  
Mujun Kim ◽  
Jung-Pyo Oh ◽  
Min Soo Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Specific Pattern ◽  
Memory Encoding ◽  
Competition Rule ◽  
Term Potentiation ◽  
Input Activity

AbstractMemory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.

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