scholarly journals Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice

2018 ◽  
Author(s):  
Yuxiao Chen ◽  
Marija Milenkovic ◽  
Ali Salahpour ◽  
Scott H. Soderling ◽  
Amy J. Ramsey
Keyword(s):  
Rho Gtpases ◽  
Pyramidal Neurons ◽  
Medium Spiny Neuron ◽  
Long Term Memory ◽  
Spine Density ◽  
Cognitive Domains ◽  
Protein Levels ◽  
Y Maze ◽  
Hippocampal Ca1

AbstractNMDA receptors are important for cognition and are implicated in neuropsychiatric disorders. GluN1 knockdown (GluN1KD) mice have reduced NMDA receptor levels, striatal spine density deficits, and cognitive impairments. However, how NMDA depletion leads to these effects is unclear. Since Rho GTPases are known to regulate spine density and cognition, we examined the levels of RhoA, Rac1, and Cdc42 signaling proteins. Striatal Rac1-pathway components are reduced in GluN1KD mice, with Rac1 and WAVE-1 deficits at 6 and 12 weeks of age. Concurrently, medium spiny neuron (MSN) spine density deficits are present in mice at these ages. To determine whether WAVE-1 deficits were causal or compensatory in relation to these phenotypes, we intercrossed GluN1KD mice with WAVE-1 overexpressing (WAVE-Tg) mice to restore WAVE-1 levels. GluN1KD-WAVE-Tg hybrids showed rescue of striatal WAVE-1 protein levels and MSN spine density, as well as selective behavioral rescue in the Y-maze and 8-arm radial maze tests. GluN1KD-WAVE-Tg mice expressed normalized WAVE-1 protein levels in the hippocampus, yet spine density of hippocampal CA1 pyramidal neurons was not significantly altered. Our data suggest a nuanced role for WAVE-1 effects on cognition and a delineation of specific cognitive domains served by the striatum. Rescue of striatal WAVE-1 and MSN spine density may be significant for goal-directed exploration and associated long-term memory in mice.

scholarly journals Five hours total sleep deprivation does not affect CA1 dendritic length or spine density

2021 ◽  
Author(s):  
Alvin T.S. Brodin ◽  
Sarolta Gabulya ◽  
Katrin Wellfelt ◽  
Tobias E. Karlsson
Keyword(s):  
Sleep Deprivation ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Memory Function ◽  
Long Term Memory ◽  
Spine Density ◽  
Dendritic Length ◽  
Dendritic Spine Density ◽  
Hippocampal Ca1

AbstractSleep is essential for long term memory function. However the neuroanatomical consequences of sleep loss are disputed. Sleep deprivation has been reported to cause both decreases and increases of dendritic spine density. Here we use Thy1-GFP expressing transgenic mice to investigate the effects of acute sleep deprivation on the dendritic architecture of hippocampal CA1 pyramidal neurons. We found that five hours of sleep deprivation had no effect on either dendritic length or dendritic spine density. Our work suggests that no major neuroanatomical changes result from one episode of sleep deprivation.

scholarly journals The Medial Temporal Lobe Is Critical for Spatial Relational Perception

2020 ◽  
Vol 32 (9) ◽  
pp. 1780-1795 ◽  
Author(s):  
Nicholas A. Ruiz ◽  
Michael R. Meager ◽  
Sachin Agarwal ◽  
Mariam Aly
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Critical Role ◽  
Long Term Memory ◽  
Term Memory ◽  
Cognitive Domains ◽  
Attention Tasks ◽  
Human Participants ◽  
Attention And Perception

The medial temporal lobe (MTL) is traditionally considered to be a system that is specialized for long-term memory. Recent work has challenged this notion by demonstrating that this region can contribute to many domains of cognition beyond long-term memory, including perception and attention. One potential reason why the MTL (and hippocampus specifically) contributes broadly to cognition is that it contains relational representations—representations of multidimensional features of experience and their unique relationship to one another—that are useful in many different cognitive domains. Here, we explore the hypothesis that the hippocampus/MTL plays a critical role in attention and perception via relational representations. We compared human participants with MTL damage to healthy age- and education-matched individuals on attention tasks that varied in relational processing demands. On each trial, participants viewed two images (rooms with paintings). On “similar room” trials, they judged whether the rooms had the same spatial layout from a different perspective. On “similar art” trials, they judged whether the paintings could have been painted by the same artist. On “identical” trials, participants simply had to detect identical paintings or rooms. MTL lesion patients were significantly and selectively impaired on the similar room task. This work provides further evidence that the hippocampus/MTL plays a ubiquitous role in cognition by virtue of its relational and spatial representations and highlights its important contributions to rapid perceptual processes that benefit from attention.

scholarly journals Social isolation impacts late-life socio-cognitive decline in APP/PS1 mice

2019 ◽  
Author(s):  
Eva Rens ◽  
Rudi D’Hooge ◽  
Ann Van der Jeugd
Keyword(s):  
Social Isolation ◽  
Short Term Memory ◽  
Social Recognition ◽  
Long Term Memory ◽  
Dependent Manner ◽  
Term Memory ◽  
Y Maze ◽  
The Social ◽  
Socially Isolated

AbstractIn this study the effects of social isolation (SI) were investigated in APP/PS1 mice. It was found that SI during adolescence has an impact on anxiogenic behaviour, such that isolated animals tend to explore a threatening environment less than non-isolated animals as assessed with the EPM test, and that this holds for both AD and non-AD mice. While no evidence was found for any differences in short-term memory as assessed by the Y-maze, long-term memory seemed to be affected in a context-dependent manner. Object memory as assessed with the NOR test was affected in APP/PS1 mice compared to WT mice, but this deficit was not induced or influenced by SI. When it comes to social recognition memory however, we found that SI exacerbated the social memory deficit in AD mice, and even induced a deficit in WTs. Associative fear memory as assessed with the PA test suggested that WTs perform better when group housed, and APP/PS1 mice better when socially isolated. The link between isolation and AD, or cognition in general, may be more complex than initially thought. The effect of isolation may not be the same for AD versus non-AD subjects.

scholarly journals CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Xiao-Wen Yu ◽  
Daniel M Curlik ◽  
M Matthew Oh ◽  
Jerry CP Yin ◽  
John F Disterhoft
Keyword(s):  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Memory Deficits ◽  
Camp Response Element Binding ◽  
Intrinsic Excitability ◽  
Long Term Memory ◽  
Term Memory ◽  
Age Related

The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline.

scholarly journals Selectively increasing GHS-R1a expression in dCA1 excitatory/inhibitory neurons have opposite effects on memory encoding

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nan Li ◽  
Na Li ◽  
Fenghua Xu ◽  
Ming Yu ◽  
Zichen Qiao ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Memory Performance ◽  
Critical Role ◽  
Inhibitory Neurons ◽  
Long Term Memory ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Term Memory ◽  
Selective Increase

Abstract Aim Growth hormone secretagogue receptor 1a (GHS-R1a) is widely distributed in brain including the hippocampus. Studies have demonstrated the critical role of hippocampal ghrelin/GHS-R1a signaling in synaptic physiology, memory and cognitive dysfunction associated with Alzheimer’s disease (AD). However, current reports are inconsistent, and the mechanism underlying memory modulation of GHS-R1a signaling is uncertain. In this study, we aim to investigate the direct impact of selective increase of GHS-R1a expression in dCA1 excitatory/inhibitory neurons on learning and memory. Methods Endogenous GHS-R1a distribution in dCA1 excitatory/inhibitory neurons was assessed by fluorescence in situ hybridization. Cre-dependent GHS-R1a overexpression in excitatory or inhibitory neurons was done by stereotaxic injection of aav-hSyn-DIO-hGhsr1a-2A-eGFP virus in dCA1 region of vGlut1-Cre or Dlx5/6-Cre mice respectively. Virus-mediated GHS-R1a upregulation in dCA1 neurons was confirmed by quantitative RT-PCR. Different behavioral paradigms were used to evaluate long-term memory performance. Results GHS-R1a is distributed both in dCA1 excitatory pyramidal neurons (αCaMKII+) and in inhibitory interneurons (GAD67+). Selective increase of GHS-R1a expression in dCA1 pyramidal neurons impaired spatial memory and object-place recognition memory. In contrast, selective increase of GHS-R1a expression in dCA1 interneurons enhanced long-term memory performance. Our findings reveal, for the first time, a neuronal type-specific role that hippocampal GHS-R1a signaling plays in regulating memory. Therefore, manipulating GHS-R1a expression/activity in different subpopulation of neurons may help to clarify current contradictory findings and to elucidate mechanism of memory control by ghrelin/GHS-R1a signaling, under both physiological and pathological conditions such as AD.

scholarly journals Early β adrenoceptor dependent time window for fear memory persistence in APPswe/PS1dE9 mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Smitha Karunakaran
Keyword(s):  
Fear Conditioning ◽  
Time Window ◽  
Fear Memory ◽  
Long Term Memory ◽  
Term Memory ◽  
Contextual Fear ◽  
Adrenoceptor Agonist ◽  
Hippocampal Ca1 ◽  
Memory Persistence

AbstractIn this study we demonstrate that 2 month old APPswe/PS1dE9 mice, a transgenic model of Alzheimer’s disease, exhibited intact short-term memory in Pavlovian hippocampal—dependent contextual fear learning task. However, their long-term memory was impaired. Intra-CA1 infusion of isoproterenol hydrochloride, the β-adrenoceptor agonist, to the ventral hippocampus of APPswe/PS1dE9 mice immediately before fear conditioning restored long-term contextual fear memory. Infusion of the β-adrenoceptor agonist + 2.5 h after fear conditioning only partially rescued the fear memory, whereas infusion at + 12 h post conditioning did not interfere with long-term memory persistence in this mouse model. Furthermore, Intra-CA1 infusion of propranolol, the β-adrenoceptor antagonist, administered immediately before conditioning to their wildtype counterpart impaired long-term fear memory, while it was ineffective when administered + 4 h and + 12 h post conditioning. Our results indicate that, long-term fear memory persistence is determined by a unique β-adrenoceptor sensitive time window between 0 and + 2.5 h upon learning acquisition, in the ventral hippocampal CA1 of APPswe/PS1dE9 mice. On the contrary, β-adrenoceptor agonist delivery to ventral hippocampal CA1 per se did not enhance innate anxiety behaviour in open field test. Thus we conclude that, activation of learning dependent early β-adrenoceptor modulation underlies and is necessary to promote long-term fear memory persistence in APPswe/PS1dE9.

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