Forepaw Sensorimotor Deprivation in Early Life Leads to the Impairments on Spatial Memory and Synaptic Plasticity in Rats

To investigate the influence of forepaw sensorimotor deprivation on memory and synaptic plasticity, Sprague-Dawley rats were divided into two groups: a sham-operated group and a group deprived of forepaw sensorimotor function by microsurgical operation at postnatal day 13 (PN13). Behavioral and electrophysiological studies were performed at PN25, PN35, PN45, and PN60. Open field test was used to assess the spontaneous locomotor activity. Morris water maze was used to evaluate spatial reference learning and memory. The long-term potentiation (LTP) in the medial perforant path—dentate gyrus (MPP-DG) pathway was examined with hippocampal slices. We found that forepaw sensorimotor deprivation did not affect spontaneous activity of the rats. However, spatial reference learning and memory were significantly impaired in their early life (PN25, PN35, and PN45). In accordance with the behavior results, LTP in MPP-DG pathway was significantly suppressed in their early life. These data demonstrated that forepaw sensorimotor deprivation led to the impairments on spatial memory via inducing pronounced deficits in the MPP-DG pathway to exhibit LTP, one of the major cellular mechanisms underlying learning and memory.

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Synaptic Plasticity and its Modulation by Alcohol

Brain Plasticity ◽

10.3233/bpl-190089 ◽

2020 ◽

Vol 6 (1) ◽

pp. 103-111 ◽

Cited By ~ 2

Author(s):

Yosef Avchalumov ◽

Chitra D. Mandyam

Keyword(s):

Synaptic Plasticity ◽

Learning And Memory ◽

Dorsal Striatum ◽

Long Term Potentiation ◽

Brain Regions ◽

Public Health Issue ◽

Cellular Mechanisms ◽

Brain Disorder ◽

The Brain

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.

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Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice

Journal of Neurophysiology ◽

10.1152/jn.00297.2014 ◽

2014 ◽

Vol 112 (8) ◽

pp. 1916-1924 ◽

Cited By ~ 16

Author(s):

Guan Cao ◽

Kristen M. Harris

Keyword(s):

Hippocampal Slices ◽

Long Term Potentiation ◽

Sprague Dawley ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Cellular Mechanisms ◽

Adult Rats ◽

Area Ca1 ◽

Hippocampal Area ◽

Theta Burst

Hippocampal long-term potentiation (LTP) is a model system for studying cellular mechanisms of learning and memory. Recent interest in mechanisms underlying the advantage of spaced over massed learning has prompted investigation into the effects of distributed episodes of LTP induction. The amount of LTP induced in hippocampal area CA1 by one train (1T) of theta-burst stimulation (TBS) in young Sprague-Dawley rats was further enhanced by additional bouts of 1T given at 1-h intervals. However, in young Long-Evans (LE) rats, 1T did not initially saturate LTP. Instead, a stronger LTP induction paradigm using eight trains of TBS (8T) induced saturated LTP in hippocampal slices from both young and adult LE rats as well as adult mice. The saturated LTP induced by 8T could be augmented by another episode of 8T following an interval of at least 90 min. The success rate across animals and slices in augmenting LTP by an additional episode of 8T increased significantly with longer intervals between the first and last episodes, ranging from 0% at 30- and 60-min intervals to 13–66% at 90- to 180-min intervals to 90–100% at 240-min intervals. Augmentation above initially saturated LTP was blocked by the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV). These findings suggest that the strength of induction and interval between episodes of TBS, as well as the strain and age of the animal, are important components in the augmentation of LTP.

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Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice

Journal of Neurophysiology ◽

10.1152/jn.00105.2003 ◽

2003 ◽

Vol 90 (1) ◽

pp. 32-38 ◽

Cited By ~ 23

Author(s):

David J. Froc ◽

Brennan Eadie ◽

Amanda M. Li ◽

Karl Wodtke ◽

Maric Tse ◽

...

Keyword(s):

Synaptic Plasticity ◽

Dentate Gyrus ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Significant Degree ◽

Perforant Path ◽

High Frequency Stimulation ◽

Synaptic Efficacy ◽

Term Potentiation ◽

Effects Of Aging

Hippocampal slices obtained from C57BL/6 mice (3–25 mo) were used to investigate the effects of aging on excitatory postsynaptic potentials (EPSPs) elicited in dentate gyrus with lateral perforant path stimulation. The maximal amplitude of the EPSP, as well as the degree of paired-pulse facilitation, was significantly reduced in animals aged 12 mo or more compared with younger animals (<12 mo). Although all animals showed equivalent short-term potentiation (STP) in response to high-frequency stimulation, this did not translate into a long-lasting increase in synaptic efficacy in the older animals. A significant degree of long-term potentiation (LTP) of synaptic efficacy was only observed in animals <12 mo of age when measured 30 min after induction. Blocking GABAA-mediated inhibition significantly enhanced STP in younger and older animals; however, a significant degree of LTP was again only observed in slices taken from younger animals. These data indicate that the lateral perforant path input to the dentate gyrus is altered by the aging process, and that this results in a reduction in the capacity of this input to exhibit long-lasting synaptic plasticity.

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LIM-Kinases in Synaptic Plasticity, Memory, and Brain Diseases

Cells ◽

10.3390/cells10082079 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2079

Author(s):

Youssif Ben Zablah ◽

Haiwang Zhang ◽

Radu Gugustea ◽

Zhengping Jia

Keyword(s):

Synaptic Plasticity ◽

Learning And Memory ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Long Term Potentiation ◽

Autism Spectrum ◽

Brain Diseases ◽

Actin Binding ◽

Structural Basis ◽

Cellular Mechanisms

Learning and memory require structural and functional modifications of synaptic connections, and synaptic deficits are believed to underlie many brain disorders. The LIM-domain-containing protein kinases (LIMK1 and LIMK2) are key regulators of the actin cytoskeleton by affecting the actin-binding protein, cofilin. In addition, LIMK1 is implicated in the regulation of gene expression by interacting with the cAMP-response element-binding protein. Accumulating evidence indicates that LIMKs are critically involved in brain function and dysfunction. In this paper, we will review studies on the roles and underlying mechanisms of LIMKs in the regulation of long-term potentiation (LTP) and depression (LTD), the most extensively studied forms of long-lasting synaptic plasticity widely regarded as cellular mechanisms underlying learning and memory. We will also discuss the involvement of LIMKs in the regulation of the dendritic spine, the structural basis of synaptic plasticity, and memory formation. Finally, we will discuss recent progress on investigations of LIMKs in neurological and mental disorders, including Alzheimer’s, Parkinson’s, Williams–Beuren syndrome, schizophrenia, and autism spectrum disorders.

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Attenuated LTP in Hippocampal Dentate Gyrus Neurons of Mice Deficient in the PAF Receptor

Journal of Neurophysiology ◽

10.1152/jn.2001.85.1.384 ◽

2001 ◽

Vol 85 (1) ◽

pp. 384-390 ◽

Cited By ~ 46

Author(s):

Chu Chen ◽

Jeffrey C. Magee ◽

Victor Marcheselli ◽

Mattie Hardy ◽

Nicolas G. Bazan

Keyword(s):

Synaptic Plasticity ◽

Dentate Gyrus ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Perforant Path ◽

High Frequency Stimulation ◽

Wild Type ◽

In The Wild ◽

Paf Receptor ◽

Deficient Mice

Platelet-activating factor (PAF), a bioactive lipid (1- O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A2and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 ± 14%, mean ± SE; n = 32) when compared with that in wild-type mice (219 ± 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 μM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 μM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.

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Stimulation of Perforant Path Fibers Induces LTP Concurrently in Amygdala and Hippocampus in Awake Freely Behaving Rats

Neural Plasticity ◽

10.1155/2013/565167 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

J. Harry Blaise ◽

Rachel A. Hartman

Keyword(s):

Learning And Memory ◽

Basolateral Amygdala ◽

Peak Level ◽

Long Term Potentiation ◽

Perforant Path ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Term Potentiation ◽

Freely Behaving ◽

Stimulation Of

Long-term potentiation (LTP) which has long been considered a cellular model for learning and memory is defined as a lasting enhancement in synaptic transmission efficacy. This cellular mechanism has been demonstrated reliably in the hippocampus and the amygdala—two limbic structures implicated in learning and memory. Earlier studies reported on the ability of cortical stimulation of the entorhinal cortex to induce LTP simultaneously in the two sites. However, to retain a stable baseline of comparison with the majority of the LTP literature, it is important to investigate the ability of fiber stimulation such as perforant path activation to induce LTP concurrently in both structures. Therefore, in this paper we report on concurrent LTP in the basolateral amygdala (BLA) and the dentate gyrus (DG) subfield of the hippocampus induced by theta burst stimulation of perforant path fibers in freely behaving Sprague-Dawley rats. Our results indicate that while perforant path-evoked potentials in both sites exhibit similar triphasic waveforms, the latency and amplitude of BLA responses were significantly shorter and smaller than those of DG. In addition, we observed no significant differences in either the peak level or the duration of LTP between DG and BLA.

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Developmental onset of enduring long-term potentiation in mouse hippocampus

10.1101/787192 ◽

2019 ◽

Author(s):

Olga I. Ostrovskaya ◽

Guan Cao ◽

Cagla Eroglu ◽

Kristen M. Harris

Keyword(s):

Synaptic Plasticity ◽

Learning And Memory ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Mouse Strains ◽

Developmental Profile ◽

Important Species ◽

Term Potentiation ◽

Mouse Hippocampus

ABSTRACTAnalysis of long-term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L-LTP), lasting >3 hours, occurs abruptly at postnatal day 12 (P12) in rat hippocampus. The goal here was to determine the developmental profile of synaptic plasticity leading to L-LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6 and Fmr1−/y on the C57BL/6 background, and 129SVE and Hevin−/− (Sparcl1−/−) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse-induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10-P35 in the expression of short-term potentiation (STP), lasting ≤ one hour. In the 129SVE mice, L-LTP onset (>25% of slices) occurred by 3 weeks, reliable L-LTP (>50% slices) was achieved by 4 weeks, and Hevin−/− advanced this profile by one week. In the C57BL/6 mice, L-LTP onset occurred significantly later, over 3-4 weeks, and reliability was not achieved until 5 weeks. Although some of the Fmr1−/y mice showed L-LTP before 3 weeks, reliable L-LTP also was not achieved until 5 weeks. Two bouts of TBS separated by ≥90 minutes advanced the onset age of L-LTP in rats from P12 to P10. In contrast, L-LTP onset was not advanced in any of the mouse genotypes by multiple bouts of TBS at 90 or 180 minute intervals. These findings show important species differences in the onset of STP and L-LTP, which occur at the same age in rats but are sequentially acquired in mice.SIGNIFICANCE STATEMENTLong-term potentiation (LTP) is a cellular mechanism of learning and memory. Knowing the developmental profile for LTP provides a basis for investigating developmental abnormalities leading to intellectual disabilities and other neurodevelopmental disorders. Here we explore the developmental profile of LTP onset in two wild type mouse strains, C57BL/6 and 129SVE, together with Fmr1−/y and Hevin−/− (Sparcl1−/−) mutations that produce abnormalities in synaptic structure, plasticity, and development. Our data provide a foundation for future investigations into connections between structural and functional plasticity leading to developmental anomalies in the brain.

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Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.1997.77.6.3013 ◽

1997 ◽

Vol 77 (6) ◽

pp. 3013-3020 ◽

Cited By ~ 154

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.

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2.45 GHz microwave radiation impairs learning, memory, and hippocampal synaptic plasticity in the rat

Toxicology and Industrial Health ◽

10.1177/0748233718798976 ◽

2018 ◽

Vol 34 (12) ◽

pp. 873-883 ◽

Cited By ~ 1

Author(s):

Narges Karimi ◽

Mahnaz Bayat ◽

Masoud Haghani ◽

Hamed Fahandezh Saadi ◽

Gholam Reza Ghazipour

Keyword(s):

Synaptic Plasticity ◽

Learning And Memory ◽

Continuous Wave ◽

Glutamate Release ◽

Average Power ◽

Field Potential ◽

Long Term Potentiation ◽

Whole Body ◽

Spatial Learning And Memory ◽

Hippocampal Synaptic Plasticity

Microwave (MW) radiation has a close relationship with neurobehavioral disorders. Due to the widespread usage of MW radiation, especially in our homes, it is essential to investigate the direct effect of MW radiation on the central nervous system. Therefore, this study was carried out to determine the effect of MW radiation on memory and hippocampal synaptic plasticity. The rats were exposed to 2.45 GHz MW radiation (continuous wave with overall average power density of 0.016 mW/cm2 and overall average whole-body specific absorption rate value of 0.017 W/kg) for 2 h/day over a period of 40 days. Spatial learning and memory were tested by radial maze and passive avoidance tests. We evaluated the synaptic plasticity and hippocampal neuronal cells number by field potential recording and Giemsa staining, respectively. Our results showed that MW radiation exposure decreased the learning and memory performance that was associated with decrement of long-term potentiation induction and excitability of CA1 neurons. However, MW radiation did not have any effects on short-term plasticity and paired-pulse ratio as a good indirect index for measurement of glutamate release probability. The evaluation of hippocampal morphology indicated that the neuronal density in the hippocampal CA1 area was significantly decreased by MW.

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PKA and Ube3a regulate SK2 channel trafficking to promote synaptic plasticity in hippocampus: Implications for Angelman Syndrome

Scientific Reports ◽

10.1038/s41598-020-66790-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Jiandong Sun ◽

Yan Liu ◽

Guoqi Zhu ◽

Caleb Cato ◽

Xiaoning Hao ◽

...

Keyword(s):

Synaptic Plasticity ◽

Angelman Syndrome ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Synaptic Membranes ◽

Channel Trafficking ◽

Over Expression ◽

Terminal Domain ◽

Complex Interactions ◽

Term Potentiation

Abstract The ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca2+-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis. Here, we report that PKA activation restores theta burst stimulation (TBS)-induced long-term potentiation (LTP) in hippocampal slices from AS mice by enhancing SK2 internalization. While TBS-induced SK2 endocytosis is facilitated by PKA activation, SK2 recycling to synaptic membranes after TBS is inhibited by Ube3a. Molecular and cellular studies confirmed that phosphorylation of SK2 in the C-terminal domain increases its ubiquitination and endocytosis. Finally, PKA activation increases SK2 phosphorylation and ubiquitination in Ube3a-overexpressing mice. Our results indicate that, although both Ube3a-mediated ubiquitination and PKA-induced phosphorylation reduce synaptic SK2 levels, phosphorylation is mainly involved in TBS-induced endocytosis, while ubiquitination predominantly inhibits SK2 recycling. Understanding the complex interactions between PKA and Ube3a in the regulation of SK2 synaptic levels might provide new platforms for developing treatments for AS and various forms of autism.

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