Disc1 gene down-regulation impaired synaptic plasticity and recognition memory via disrupting neural activity in mice

2021 ◽  
Vol 171 ◽  
pp. 84-90
Author(s):  
Ze Yang ◽  
Xi Xiao ◽  
Runwen Chen ◽  
Xinxin Xu ◽  
Wanzeng Kong ◽  
...  
2021 ◽  
Vol 94 ◽  
pp. 196-209
Author(s):  
Yuxing Yan ◽  
Xinxin Xu ◽  
Renwen Chen ◽  
Shian Wu ◽  
Zhuo Yang ◽  
...  

2021 ◽  
pp. 1-12
Author(s):  
Hanne Lie Kjærstad ◽  
Julian Macoveanu ◽  
Gitte Moos Knudsen ◽  
Sophia Frangou ◽  
K. Luan Phan ◽  
...  

Abstract Background Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (HCs). Methods We compared neural activity and fronto-limbic functional connectivity during emotion regulation in response to aversive v. neutral pictures in patients recently diagnosed with BD (n = 78) in full/partial remission, their URs (n = 35), and HCs (n = 56). Results Patients showed hypo-activity in the left dorsomedial, dorsolateral, and ventrolateral prefrontal cortex (DMPFC and DLPFC) during emotion regulation while viewing aversive pictures compared to HCs, with URs displaying intermediate neural activity in these regions. There were no significant differences between patients with BD and HCs in functional connectivity from the amygdala during emotion regulation. However, exploratory analysis indicated that URs displayed more negative amygdala–DMPFC coupling compared with HCs and more negative amygdala-cingulate DLPFC coupling compared to patients with BD. At a behavioral level, patients and their URs were less able to dampen negative emotions in response aversive pictures. Conclusions The findings point to deficient recruitment of prefrontal resources and more negative fronto-amygdala coupling as neural markers of impaired emotion regulation in recently diagnosed remitted patients with BD and their URs, respectively.


2020 ◽  
Vol 12 ◽  
Author(s):  
Emma Arvidsson ◽  
Sarolta Gabulya ◽  
Alvin Tore Brodin ◽  
Tobias Erik Karlsson ◽  
Lars Olson

Structural synaptic reorganizations needed to permanently embed novel memories in the brain involve complex plasticity-enhancing and plasticity-inhibiting systems. Increased neural activity is linked to rapid downregulation of Nogo receptor 1 (NgR1), needed to allow local structural synaptic plasticity. This local regulation of plasticity is thought to be moderated by global systems, such as the ascending cholinergic and monoaminergic systems, adding significance to locally increased neural activity. Here we address the reverse possibility that the global systems may also be influenced by the status of local plasticity. Using NgR1-overexpressing mice, with impaired plasticity and long-term memory, we measured the ability to release dopamine (DA), implicated in regulating plasticity and memory. In vivo chronoamperometric recording with high temporal and spatial resolution revealed severe impairment of potassium chloride (KCl)-induced increase of extracellular DA in the dorsal striatum of mice overexpressing NgR1 in forebrain neurons. A similar, but lesser, impairment of DA release was seen following amphetamine delivery. In contrast, potassium chloride-evoked DA release in NgR1 knockout (KO) mice led to increased levels of extracellular DA. That NgR1 can impair DA signaling, thereby further dampening synaptic plasticity, suggests a new role for NgR1 signaling, acting in synergy with DA signaling to control synaptic plasticity.Significance Statement:The inverse correlation between local NgR1 levels and magnitude of KCl-inducible amounts of DA release in the striatum reinforces the rule of NgR1 as a regulator of structural synaptic plasticity and suggests synergy between local and global plasticity regulating systems.


2010 ◽  
Vol 2010.16 (0) ◽  
pp. 311-312
Author(s):  
Sho KOBAYASHI ◽  
Masataka ARAI ◽  
Kazumasa ITOI ◽  
Susumu KUDO

2014 ◽  
Vol 8 (4) ◽  
pp. 598-610 ◽  
Author(s):  
Shijia Li ◽  
Riklef Weerda ◽  
Christopher Milde ◽  
Oliver T. Wolf ◽  
Christiane M. Thiel

1999 ◽  
Vol 77 (9) ◽  
pp. 735-737 ◽  
Author(s):  
John TR Isaac ◽  
Roger A Nicoll ◽  
Robert C Malenka

Excitatory synaptic transmission in the mammalian brain is mediated primarily by α-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors that are thought to be co-localized at individual synapses. However, recent electrophysiological and anatomical data suggest that the synaptic localization of AMPA and NMDA receptors may be independently regulated by neural activity. These data are reviewed here and the implications of these findings for the mechanisms underlying synaptic plasticity are discussed.Key words: glutamate receptor, long-term potentiation (LTP), synaptic plasticity, hippocampus, cortex.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liv Mahnke ◽  
Erika Atucha ◽  
Eneko Pina-Fernàndez ◽  
Takashi Kitsukawa ◽  
Magdalena M. Sauvage

AbstractThe sense of familiarity for events is crucial for successful recognition memory. However, the neural substrate and mechanisms supporting familiarity remain unclear. A major controversy in memory research is whether the parahippocampal areas, especially the lateral entorhinal (LEC) and the perirhinal (PER) cortices, support familiarity or whether the hippocampus (HIP) does. In addition, it is unclear if LEC, PER and HIP interact within this frame. Here, we especially investigate if LEC and PER's contribution to familiarity depends on hippocampal integrity. To do so, we compare LEC and PER neural activity between rats with intact hippocampus performing on a human to rat translational task relying on both recollection and familiarity and rats with hippocampal lesions that have been shown to then rely on familiarity to perform the same task. Using high resolution Immediate Early Gene imaging, we report that hippocampal lesions enhance activity in LEC during familiarity judgments but not PER’s. These findings suggest that different mechanisms support familiarity in LEC and PER and led to the hypothesis that HIP might exert a tonic inhibition on LEC during recognition memory that is released when HIP is compromised, possibly constituting a compensatory mechanism in aging and amnesic patients.


2020 ◽  
Author(s):  
Han Lu ◽  
Júlia V. Gallinaro ◽  
Claus Normann ◽  
Stefan Rotter ◽  
Ipek Yalcin

AbstractSynapse formation and network rewiring is key to build neural circuits during development and has been widely observed in adult brains. Maintaining neural activity with the help of synaptic plasticity is essential to enable normal brain function. The model of homeostatic structural plasticity (HSP) was proposed to reflect the homeostatic regulation of neural activity and explain structural changes seen after perturbations. However, the specific temporal profile of such plastic responses has not yet been elucidated in experiments. To address this issue, we combined computational modeling and mouse optogenetic stimulation experiments. Our model predicted that within 48 h post-stimulation, neural activity returns to baseline, while the connectivity among stimulated neurons follows a very specific transient increase and decrease. To capture such dynamics experimentally in vivo, we activated the pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and 48 h post-stimulation. Cortical hyperactivity as demonstrated by robust c-Fos expression persisted up to 1.5 h and decayed to baseline after 24 h. However, spine density and spine head volume were increased at 24 h and decreased at 48 h. Synaptic proteins VGLUT1 and PSD-95 were also upregulated and downregulated at 24 h and 48 h, respectively, while the calmodulin-binding protein neurogranin was translocated from the soma to the dendrite. Additionally, lasting astrocyte reactivation and microglia proliferation were observed, suggesting a role of neuron-glia interaction. All this corroborates the interpretation of our experimental results in terms of homeostatic structural plasticity. Our results bring important insights of how external stimulation modulates synaptic plasticity and behaviors.Significance StatementWe combined both computational modeling and mouse experiments to clarify the temporal dynamics of structural and functional homeostatic plasticity in response to external stimulation. We observed the biphasic regulation of spine density, spine head volume, and synaptic proteins at 24 h and 48 h after the optogenetic stimulation of the anterior cingulate cortex, when the neural activity was restored to the homeostatic level. The orchestrated regulation of presynaptic VGLUT1 and postsynaptic PSD-95, as well as the soma-dendrites translocation of neurogranin, suggested an elaborate molecular mechanism underlying homeostatic structural plasticity. Our experimental results thus corroborated the theoretical concept of homeostatic structural plasticity and revealed the temporal evolution of structural and functional plasticity.


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