scholarly journals Protein phase separation provides long-term memory of transient spatial stimuli

2018 ◽  
Author(s):  
Elliot Dine ◽  
Agnieszka A. Gil ◽  
Giselle Uribe ◽  
Clifford P. Brangwynne ◽  
Jared E. Toettcher

AbstractProtein/RNA clusters arise frequently in spatially-regulated biological processes, from the asymmetric distribution of P granules and PAR proteins in developing embryos to localized receptor oligomers in migratory cells. This co-occurrence suggests that protein clusters might possess intrinsic properties that make them a useful substrate for spatial regulation. Here, we demonstrate that protein droplets show a robust form of spatial memory, maintaining the spatial pattern of an inhibitor of droplet formation long after it has been removed. Despite this persistence, droplets can be highly dynamic, continuously exchanging monomers with the diffuse phase. We investigate the principles of biophysical spatial memory in three contexts: a computational model of phase separation; a novel optogenetic system where light can drive rapid, localized dissociation of liquid-like protein droplets; and membrane-localized signal transduction from clusters of receptor tyrosine kinases. Our results suggest that the persistent polarization underlying many cellular and developmental processes could arise through a simple biophysical process, without any additional requirement for biochemical positive and negative feedback loops.HighlightsWe introduce PixELLs, an optogenetic system for protein droplet disassembly.Modeling and experiments demonstrate long-term memory of local droplet dissociation.Droplets ‘remember’ spatial stimuli in nuclei, the cytosol and on cell membranes.FGFR-optoDroplets convert transient local inputs to persistent cytoskeletal responses.

2018 ◽  
Author(s):  
Lea M. Bartsch ◽  
Vanessa M. Loaiza ◽  
Lutz Jäncke ◽  
Klaus Oberauer ◽  
Jarrod A. Lewis-Peacock

AbstractMaintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance.HighlightsRepeated reading, refreshing, and elaboration are differentiable in brain activation patterns in both young and older adults.Elaboration selectively improved long-term memory for young adults, and the size of the benefit was related to the neural separability of elaboration from other processes.Older adults implemented a sub-optimal form of elaboration, and this may be a factor contributing to age-related deficits in long-term memory.Ethics statementThe study was approved by the ethical review board of the canton of Zurich (BASEC-No. 2017-00190) and all subjects gave informed written consent in accordance with the Declaration of Helsinki.Data and code availability statementAll behavioral data and analysis scripts can be assessed on the Open Science Framework (osf.io/p2h8b/). The fMRI data that support the findings of this study are available on request from the corresponding author, LMB. The fMRI data are not publicly available due to restrictions of the Swiss Ethics Committees on research involving humans regarding data containing information that could compromise the privacy of research participants.


2019 ◽  
Vol 38 (4) ◽  
pp. 312-318 ◽  
Author(s):  
Fernanda Gumilar ◽  
Cristina Bras ◽  
Patricia Aggio ◽  
Sergio Domínguez ◽  
Mariana Bartos ◽  
...  

Pregnant rats were treated with 0.3 and 0.6 mg cadmium (CdCl2)/kg injected subcutaneously on a daily basis from gestational day 7 to day 15 (organogenesis period). One control group was not injected and other received saline. The 45-day-old offspring were tested in a step-down inhibitory avoidance to evaluate short-term and long-term memory and in a radial maze for the study of spatial memory. These studies showed that gestational exposure to 0.6 mg Cd/kg produced in the male offspring a significant impairment in the retention of long-term memory evaluated 24 hours after training in the step-down inhibitory avoidance. The radial maze also demonstrated that the male offspring prenatally exposed to 0.6 mg Cd presented a significant deficit in the retention of spatial memory evaluated 42 days after training. These results demonstrate that the exposure to Cd during organogenesis may affect the retention of some types of memory.


2016 ◽  
Vol 17 (4) ◽  
pp. 377-387 ◽  
Author(s):  
Heiko C. Bergmann ◽  
Sander M. Daselaar ◽  
Guillén Fernández ◽  
Roy P. C. Kessels

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Panayiotis Tsokas ◽  
Changchi Hsieh ◽  
Yudong Yao ◽  
Edith Lesburguères ◽  
Emma Jane Claire Wallace ◽  
...  

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.


Author(s):  
Tanisse Teale

A majority of research into memory formation and consolidation is commonly focused on adult brains and organisms. Our work focuses on the mechanisms of memory within the developing, juvenile brain in an attempt to provide a more full understanding of the underlying neural mechanisms of memory formation, consolidation and storage. During juvenile development, the brain undergoes important remodeling and synaptic pruning towards shaping the adult brain. Thus, during this time, memories may be lost through the remodeling of hippocampal-neocortical connections. The significance of comparing juvenile and adult memory processes is critical in understanding the structural changes that occur within memory-specific circuits associated with long-term memory formation. To provide a comparison of the neurobehavioral aspects of long-term memory formation in juveniles and adults, we trained Long Evan’s rats on a spatial task on postnatal days 16, 18, 20, 25, 30 or 50 (adults). Each age group was then tested for memory recall 24 hours or 3 weeks later. We noted that memory recall showed a dramatic change at postnatal day 20 such that memory recall at postnatal day 25 was similar to adult levels. We then used immunohistochemistry to quantify and analyze neural activity patterns in brain regions thought to underlie the short- and long-term storage of spatial memories. Identification of these regional activity changes during juvenile periods and comparison with adults allows us to explore the function and organization of interacting brain regions in long-term spatial memory storage during development.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Guorong Tao ◽  
Yan Luo ◽  
Qingsheng Xue ◽  
Guohui Li ◽  
Yongchang Tan ◽  
...  

Sevoflurane exposures were demonstrated to induce neurotoxicity in the developing brain in both human and animal studies. However, there is no effective approach to reverse it. The present study aimed to evaluate the feasibility of utilizing docosahexaenoic acid (DHA) to prevent sevoflurane-induced neurotoxicity. P6 (postnatal 6 days) mice were administrated DHA after exposure to 3% sevoflurane for two hours daily in three consecutive days. Molecular expressions of synaptic makers (PSD95, synaptophysin) and synaptic morphological changes were investigated by Western blot analysis and transmission electron microscopy, respectively. Meanwhile, Morris water maze test was used to assess spatial memory of mice at P31 (postnatal 31 days). DHA restored sevoflurane-induced decreased level of PSD95 and synaptophysin expressions and increased PSD areas and also improved long-term spatial memory. These results suggest that DHA could rescue synaptogenesis impairment and long-term memory deficits in postnatal caused by multiple sevoflurane exposures.


Cell Systems ◽  
2018 ◽  
Vol 6 (6) ◽  
pp. 655-663.e5 ◽  
Author(s):  
Elliot Dine ◽  
Agnieszka A. Gil ◽  
Giselle Uribe ◽  
Clifford P. Brangwynne ◽  
Jared E. Toettcher

2019 ◽  
Author(s):  
Anders M Fjell ◽  
Markus H. Sneve ◽  
Donatas Sederevicius ◽  
Øystein Sørensen ◽  
Stine K Krogsrud ◽  
...  

AbstractEpisodic memory function improves through childhood and adolescence, in part due to structural maturation of the medial temporal cortex. Although partly different processes support long-term memory over shorter vs. longer intervals, memory is usually assessed after less than an hour. The aim of the present study was to test whether there are unique developmental changes in extended memory, and whether these are related to structural maturation of sub-regions of the hippocampus. 650 children and adolescents from 4.1 to 24.8 years were assessed in total 962 times (mean interval ≈ 1.8 years). Memory was assessed by the California Verbal Learning Test (CVLT) and the Rey Complex Figure Test (CFT). In addition to 30 min recall, an extended delay recall condition was administered ≈ 10 days after encoding. We found unique developmental effects on extended delay memory independently of 30 min recall performance. For visuo-constructive memory, this could be accounted for by visuo-constructive ability levels. Performance was modestly related to anterior and posterior hippocampal volume and mean diffusion. The relationships did not show an anterior-posterior hippocampal axis difference. In conclusion, extended delay memory shows unique development, likely due to changes in encoding depth or efficacy, or improvements of long-term consolidation processes.HighlightsUnique developmental effects on episodic memories over days rather than minutesDevelopment of visuoconstructive recall explainable by visuoconstructive abilitityDevelopment of verbal recall cannot be explained by verbal abilityModest relationships between memory and hippocampal structural features


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