scholarly journals Pyk2 in dorsal hippocampus plays a selective role in spatial memory and synaptic plasticity

2021 ◽  
Author(s):  
Vincenzo Mastrolia ◽  
Omar al Massadi ◽  
Benoit de Pins ◽  
Jean-Antoine Girault
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Dorsal Hippocampus ◽  
Training Session ◽  
Long Term Potentiation ◽  
Object Location ◽  
High Frequency Stimulation ◽  
Novel Object ◽  
Ca1 Region

Pyk2 is a Ca2+-activated non-receptor tyrosine kinase enriched in the forebrain, especially in pyramidal neurons of the hippocampus. Previous reports suggested its role in hippocampal synaptic plasticity and spatial memory but with contradictory findings possibly due to experimental conditions. Here we address this issue and show that novel object location, a simple test of spatial memory induced by a single training session, is altered in Pyk2 KO mice and that re-expression of Pyk2 in the dorsal hippocampus corrects this deficit. Bilateral targeted deletion of Pyk2 in dorsal hippocampus CA1 region also alters novel object location. Long term potentiation (LTP) in CA1 is impaired in Pyk2 KO mice using a high frequency stimulation induction protocol nut not with a theta burst protocol, explaining differences between previous reports. The same selective LTP alteration is observed in mice with Pyk2 deletion in dorsal hippocampus CA1 region. Thus, our results establish the role of Pyk2 in specific aspects of spatial memory and synaptic plasticity and show the dependence of the phenotype on the type of experiments used to reveal it. In combination with other studies they provide evidence for a selective role of non-receptor tyrosine kinases in specific aspects of hippocampal neurons synaptic plasticity.

scholarly journals Pyk2 in dorsal hippocampus plays a selective role in spatial memory and synaptic plasticity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vincenzo Mastrolia ◽  
Omar al Massadi ◽  
Benoit de Pins ◽  
Jean-Antoine Girault
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Dorsal Hippocampus ◽  
Training Session ◽  
Long Term Potentiation ◽  
Object Location ◽  
High Frequency Stimulation ◽  
Novel Object ◽  
Ca1 Region

AbstractPyk2 is a Ca2+-activated non-receptor tyrosine kinase enriched in the forebrain, especially in pyramidal neurons of the hippocampus. Previous reports suggested its role in hippocampal synaptic plasticity and spatial memory but with contradictory findings possibly due to experimental conditions. Here we address this issue and show that novel object location, a simple test of spatial memory induced by a single training session, is altered in Pyk2 KO mice and that re-expression of Pyk2 in the dorsal hippocampus corrects this deficit. Bilateral targeted deletion of Pyk2 in dorsal hippocampus CA1 region also alters novel object location. Long term potentiation (LTP) in CA1 is impaired in Pyk2 KO mice using a high frequency stimulation induction protocol but not with a theta burst protocol, explaining differences between previous reports. The same selective LTP alteration is observed in mice with Pyk2 deletion in dorsal hippocampus CA1 region. Thus, our results establish the role of Pyk2 in specific aspects of spatial memory and synaptic plasticity and show the dependence of the phenotype on the type of experiments used to reveal it. In combination with other studies, we provide evidence for a selective role of non-receptor tyrosine kinases in specific aspects of hippocampal neurons synaptic plasticity.

scholarly journals Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Enrico Faldini ◽  
Tariq Ahmed ◽  
Luc Bueé ◽  
David Blum ◽  
Detlef Balschun
Keyword(s):  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Synaptic Loss ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

scholarly journals Cornichon Homolog-3 (CNIH3) Modulates Spatial Memory in Female Mice

2019 ◽  
Author(s):  
Hannah E. Frye ◽  
Sidney B. Williams ◽  
Christopher R. Trousdale ◽  
Elliot C. Nelson ◽  
Joseph D. Dougherty ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Dorsal Hippocampus ◽  
Postsynaptic Membrane ◽  
Spatial Learning And Memory ◽  
Female Mice ◽  
Specific Effects ◽  
Hippocampal Synaptic Plasticity ◽  
Auxiliary Protein

ABSTRACTCornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein that traffics AMPARs to the postsynaptic membrane and potentiates AMPAR signaling. AMPARs are key components of hippocampal synaptic plasticity and memory formation, however the role of CNIH3 in memory has yet to be elucidated. To study the role of CNIH3 on mouse behavior, we bred and characterized a line of Cnih3-/- mice from C57BL/6 Cnih3tm1a(KOMP)Wtsi mice obtained from the Knockout Mouse Project (KOMP). In agreement with previous studies of CNIH3 in the brain, we observed concentrated expression of Cnih3 in the dorsal hippocampus, a region associated with spatial learning and memory. Therefore, we tested Cnih3+/+, Cnih3+/-, and Cnih3-/- mice in the Barnes maze paradigm to measure spatial memory. We observed no change in spatial memory in male Cnih3+/- and Cnih3-/- mice compared to male Cnih3+/+ controls, however, Cnih3-/- female mice made significantly more primary errors, had a higher primary latency, and took less efficient routes to the target in the maze compared to Cnih3+/+ female mice. Next, to investigate an enhancement of spatial memory by Cnih3 overexpression, specifically in the dorsal hippocampus, we developed an AAV5 viral construct to express wild-type Cnih3 in excitatory neurons. Female mice overexpressing Cnih3 made significantly fewer errors, had a lower primary latency to the target, and took more efficient routes to the maze target compared to YFP expressing control females. No change in spatial memory was observed in male Cnih3 overexpression mice. This study, the first to identify sex-specific effects of the AMPAR auxiliary protein CNIH3 on spatial memory, provides the groundwork for future studies investigating the role of CNIH3 on sexually dimorphic AMPAR-dependent behavior and hippocampal synaptic plasticity.

Metabotropic glutamate receptor dependent EPSP and EPSP-spike potentiation in area CA1 of the submerged rat hippocampal slice

1996 ◽  
Vol 76 (5) ◽  
pp. 3126-3135 ◽  
Author(s):  
N. A. Breakwell ◽  
M. J. Rowan ◽  
R. Anwyl
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Cell Body ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Area Ca1 ◽  
Gabaa Receptor Antagonist

1. We reexamined the important areas of conflict in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced potentiation of the field excitatory postsynaptic potential (EPSP) and, for the first time, investigated the role of mGluRs in EPSP-spike (E-S) coupling. 2. (1S,3R)-ACPD (10 microM) bath applied for 20 min consistently induced a long-lasting potentiation of the dendritic EPSP in area CA1 of submerged rat hippocampal slices, which was considerably faster in onset than described previously. 3. This effect was not associated with any change in presynaptic fiber volley but was dependent on both an intact CA3 connection, because removal of area CA3 blocked (1S,3R)-ACPD-induced potentiation, and also on functional N-methyl-D-aspartate (NMDA) receptors, because (1S,3R)-ACPD-induced potentiation was blocked by inclusion of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). 4. (1S,3R)-ACPD induced a long-lasting potentiation of the population spike (PS) amplitude that was consistently larger than that of the EPSP measured in the cell body area. This EPSP-PS (E-S) potentiation was blocked by inclusion of the gamma-aminobuturic acid-A (GABAA) receptor antagonist, picrotoxin (50 microM). 5. E-S potentiation induced by high-frequency stimulation (HFS), which was of the same magnitude as that induced by (1S,3R)-ACPD, was blocked by the mGluR-selective antagonist (+)-alpha-methyl-4-carboxyphenylglycine (+MCPG; 250 microM). +MCPG also blocked HFS-induced long-term potentiation (LTP) of the EPSP measured in the cell body. 6. These results suggest that (1S,3R)-ACPD-induced potentiation is NMDA receptor dependent, contrary to some previous findings, and provide further evidence that both synaptic and E-S potentiation induced by (1S,3R)-ACPD share common mechanisms of expression with HFS-induced LTP. The data emphasize the important role of mGluRs in induction of EPSP LTP and E-S potentiation.

Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

1997 ◽  
Vol 77 (6) ◽  
pp. 3013-3020 ◽  
Author(s):  
Hiroshi Katsuki ◽  
Yukitoshi Izumi ◽  
Charles F. Zorumski
Keyword(s):  
Synaptic Plasticity ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Stimulus Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

scholarly journals Examination of the role of cGMP in long-term potentiation in the CA1 region of the hippocampus.

1996 ◽  
Vol 3 (1) ◽  
pp. 42-48 ◽  
Author(s):  
D K Selig ◽  
M R Segal ◽  
D Liao ◽  
R C Malenka ◽  
R Malinow ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Ca1 Region ◽  
Term Potentiation

scholarly journals Biases in object location estimation: the role of camera rotations and translation

2021 ◽  
Author(s):  
Vladislava Segen
Keyword(s):  
Older Adults ◽  
Spatial Memory ◽  
Spatial Information ◽  
Location Estimation ◽  
Object Location ◽  
Systematic Bias ◽  
Accurate Representation ◽  
Object Locations ◽  
Age Related

The current study investigated a systematic bias in spatial memory in which people, following a perspective shift from encoding to recall, indicated the location of an object further to the direction of the shit. In Experiment 1, we documented this bias by asking participants to encode the position of an object in a virtual room and then indicate it from memory following a perspective shift induced by camera translation and rotation. In Experiment 2, we decoupled the influence of camera translations and camera rotations and examined also whether adding more information in the scene would reduce the bias. We also investigated the presence of age-related differences in the precision of object location estimates and the tendency to display the bias related to perspective shift. Overall, our results showed that camera translations led to greater systematic bias than camera rotations. Furthermore, the use of additional spatial information improved the precision with which object locations were estimated and reduced the bias associated with camera translation. Finally, we found that although older adults were as precise as younger participants when estimating object locations, they benefited less from additional spatial information and their responses were more biased in the direction of camera translations. We propose that accurate representation of camera translations requires more demanding mental computations than camera rotations, leading to greater uncertainty about the position of an object in memory. This uncertainty causes people to rely on an egocentric anchor thereby giving rise to the systematic bias in the direction of camera translation.

scholarly journals Role of Voltage-Dependent Calcium Channel Long-Term Potentiation (LTP) and NMDA LTP in Spatial Memory

2000 ◽  
Vol 20 (24) ◽  
pp. 9272-9276 ◽  
Author(s):  
Albert M. Borroni ◽  
Harlan Fichtenholtz ◽  
Brian L. Woodside ◽  
Timothy J. Teyler
Keyword(s):  
Spatial Memory ◽  
Calcium Channel ◽  
Long Term Potentiation ◽  
Voltage Dependent Calcium Channel ◽  
Term Potentiation ◽  
Voltage Dependent

scholarly journals Age-Related Cognitive Impairment: Role of Reduced Synaptobrevin-2 Levels in Deficits of Memory and Synaptic Plasticity

2019 ◽  
Vol 75 (9) ◽  
pp. 1624-1632 ◽  
Author(s):  
Albert Orock ◽  
Sreemathi Logan ◽  
Ferenc Deak
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Receptor Protein ◽  
Protein Levels ◽  
Ca1 Region ◽  
Age Related ◽  
Term Potentiation

AbstractCognitive impairment in the aging population is quickly becoming a health care priority, for which currently no disease-modifying treatment is available. Multiple domains of cognition decline with age even in the absence of neurodegenerative diseases. The cellular and molecular changes leading to cognitive decline with age remain elusive. Synaptobrevin-2 (Syb2), the major vesicular SNAP receptor protein, highly expressed in the cerebral cortex and hippocampus, is essential for synaptic transmission. We have analyzed Syb2 protein levels in mice and found a decrease with age. To investigate the functional consequences of lower Syb2 expression, we have used adult Syb2 heterozygous mice (Syb2+/−) with reduced Syb2 levels. This allowed us to mimic the age-related decrease of Syb2 in the brain in order to selectively test its effects on learning and memory. Our results show that Syb2+/− animals have impaired learning and memory skills and they perform worse with age in the radial arm water maze assay. Syb2+/− hippocampal neurons have reduced synaptic plasticity with reduced release probability and impaired long-term potentiation in the CA1 region. Syb2+/− neurons also have lower vesicular release rates when compared to WT controls. These results indicate that reduced Syb2 expression with age is sufficient to cause cognitive impairment.

scholarly journals Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Saatheeyavaane Bhuvanendran ◽  
Siti Najmi Syuhadaa Bakar ◽  
Yatinesh Kumari ◽  
Iekhsan Othman ◽  
Mohd. Farooq Shaikh ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Rat Model ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Mrna Levels ◽  
Post Surgery ◽  
Term Potentiation

Abstract Alzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.

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