Engram cells retain memory under retrograde amnesia Ryan, Tomás J.; Roy, Dheeraj S.; Pignatelli, Michele ...
Science (American Association for the Advancement of Science),
05/2015, Letnik:
348, Številka:
6238
Journal Article
Recenzirano
Odprti dostop
Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively ...through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is ...mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.
Creating a False Memory in the Hippocampus Ramirez, Steve; Liu, Xu; Lin, Pei-Ann ...
Science (American Association for the Advancement of Science),
07/2013, Letnik:
341, Številka:
6144
Journal Article
Recenzirano
Odprti dostop
Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram—bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure ...to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.
Memory engram storage and retrieval Tonegawa, Susumu; Pignatelli, Michele; Roy, Dheeraj S ...
Current opinion in neurobiology,
12/2015, Letnik:
35
Journal Article
Recenzirano
Odprti dostop
Highlights • We review the history of research into putative memory storage mechanisms. • We highlight recent advances catalyzed by memory engram labeling technology. • We discuss the physiological ...properties of engram cells in memory consolidation. • We describe a novel investigation into the nature of retrograde amnesia. • We propose a differentiation between the mechanism of memory storage and retrieval.
Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory engram labeling technology allows a precise ...investigation of the processes associated with the recall of a specific memory. Here, we show that engram cell excitability is transiently increased following memory reactivation. This short-term increase of engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal’s ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same engram. The state of excitability of engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.
•Memory recall induces a transient increase in engram cell excitability•The engram excitability increase is mediated by Kir2.1 channel internalization•The engram high-excitability state is associated with enhanced context recognition•Engram-specific exogenous expression of Kir2.1 channels impairs context recognition
Memory exists across different time scales. Long-term memories can last a lifetime, while working memory persists for mere seconds. In between, memories that are newly formed—or recently recalled—are more vivid than latent ones. How does this happen? The act of memory recall increases the excitability of whole engram cells for about one hour. This short-term increase of engram cell excitability facilitates synaptic access to memory content in response to relevant environmental cues.
The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of ...the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is currently unclear whether the GluN2 subtype influences NMDA receptor (NMDAR) excitotoxicity. We report that the toxicity of NMDAR-mediated Ca2+ influx is differentially controlled by the ...cytoplasmic C-terminal domains of GluN2B (CTD2B) and GluN2A (CTD2A). Studying the effects of acute expression of GluN2A/2B-based chimeric subunits with reciprocal exchanges of their CTDs revealed that CTD2B enhances NMDAR toxicity, compared to CTD2A. Furthermore, the vulnerability of forebrain neurons in vitro and in vivo to NMDAR-dependent Ca2+ influx is lowered by replacing the CTD of GluN2B with that of GluN2A by targeted exon exchange in a mouse knockin model. Mechanistically, CTD2B exhibits stronger physical/functional coupling to the PSD-95-nNOS pathway, which suppresses protective CREB activation. Dependence of NMDAR excitotoxicity on the GluN2 CTD subtype can be overcome by inducing high levels of NMDAR activity. Thus, the identity (2A versus 2B) of the GluN2 CTD controls the toxicity dose-response to episodes of NMDAR activity.
► The CTD of GluN2B promotes excitotoxicity better than that of GluN2A ► GluN2 CTD subtype differences are seen in both WT and chimeric 2A/2B subunits ► The GluN2B CTD couples to a prodeath PSD-95/nNOS-dependent CREB shut-off pathway
Martel et al. find that the two subtypes (2A versus 2B) of the GluN2 C-terminal domain differentially couple to the CREB shut-off pathway, causing distinct effects on NMDA receptor-mediated neuronal death both in vitro and in vivo.
Background The management of acromioclavicular (AC) joint dislocation remains controversial. Recently, anatomic coracoclavicular (CC) fixation with a double clavicular tunnel and three flip-buttons ...has shown promising results. This study aimed to evaluate functional and radiological outcomes in patients with high-grade AC joint dislocation treated with anatomic CC fixation using double clavicular tunnels and three flip-buttons. Methods A retrospective, unicentric study was performed. The study included patients with high-grade AC joint dislocation who underwent surgery with anatomic CC fixation using double clavicular tunnels and three flip-buttons. Demographic data were obtained from medical records. A functional evaluation using subjective shoulder value (SSV), visual analog scale (VAS), and disabilities of the arm, shoulder and hand (DASH) questionnaires was performed, and an evaluation of preoperative and postoperative comparative Zanca view images was performed. Factors associated with functional outcomes and radiological AC reduction were analyzed. Results A total of 83 patients completed follow-up and were included in the analysis. The mean SSV, VAS, and DASH scores were 92.8, 0.8, and 6.4, respectively. Patients who had complications experienced significantly worse functional outcomes (DASH: P=0.037). Suboptimal final AC reduction was observed in nine patients (11.1%), and significantly more frequently in patients older than 40 years (P=0.031) and in surgeries performed more than 7 days after injury (P=0.034). There were two reoperations (2.4%). Conclusions Anatomic CC fixation with a double clavicular tunnel and three flip-buttons leads to good functional outcomes, low complication rates, and high rates of optimal AC reduction. Conclusions Anatomic CC fixation with a double clavicular tunnel and three flip-buttons leads to good functional outcomes, low complication rates, and high rates of optimal AC reduction. Level of Evidence Level IV, case series.
Aim
To evaluate in a laboratory setting the effects of Endosequence BC Sealer HiFlow (Brasseler USA, Savannah, GA, USA), a novel calcium silicate‐based sealer developed for use in warm canal filling ...techniques, on human periodontal ligament stem cells (hPDLSCs).
Methodology
Eluates of EndoSequence BC Sealer HiFlow (BCHiF) (Brasseler USA), EndoSequence BC Sealer (BCS) (Brasseler USA) and AH Plus (AHP) (Dentsply DeTrey GmbH, Konstanz, Germany) were placed in contact with hPDLSCs. The characterization of the chemical elements of the root canal sealers was assessed using scanning electron microscopy and energy‐dispersive X‐ray analysis (SEM‐EDX). Inductively coupled plasma‐mass spectrometry (ICP‐MS) was used to determine the ion release of the sealers. MTT assay and wound healing techniques were used to determine cell viability and migration, respectively. Cell morphology and cell attachment were assessed using a direct contact technique of hPDLSCs onto the surface of the sealers and analysed by SEM. The bioactivity potential was carried out with the Alizarin Red and qPCR testing methods. The statistical differences were evaluated using one‐way anova and Tukey’s test (P < 0.05).
Results
ICP‐MS and EDX revealed significantly more zirconium in BCHiF than BCS (P < 0.05), whereas BCS had slightly higher levels of Ca2+ than BCHiF (P < 0.05). The cell viability assay revealed no relevant differences between BCS and BCHiF when compared with the control group (P > 0.05). Both BCS and BCHiF had similar rates of cell migration to the control group at 24 and 48 h. Cell morphology and adhesion capacity were also similar for BCS and BCHiF groups, whilst the AHP group was associated with reduced adhesion capacity. The Alizarin Red assay revealed a significant difference between the BCS and the control group (P < 0.001), as well as for the BCHiF group (P < 0.001). Finally, BCS and BCHiF promoted overexpression of osteo/cementogenic genes.
Conclusions
In general, EndoSequence BC Sealer HiFlow possesses suitable biological properties to be safely used as a root canal filling material and promote increased expression of oste/cementogenic genes by hPDLSCs.
Memory, defined as the storage and use of learned information in the brain, is necessary to modulate behavior and critical for animals to adapt to their environments and survive. Despite being a ...cornerstone of brain function, questions surrounding the molecular and cellular mechanisms of how information is encoded, stored, and recalled remain largely unanswered. One widely held theory is that an engram is formed by a group of neurons that are active during learning, which undergoes biochemical and physical changes to store information in a stable state, and that are later reactivated during recall of the memory. In the past decade, the development of engram labeling methodologies has proven useful to investigate the biology of memory at the molecular and cellular levels. Engram technology allows the study of individual memories associated with particular experiences and their evolution over time, with enough experimental resolution to discriminate between different memory processes: learning (encoding), consolidation (the passage from short-term to long-term memories), and storage (the maintenance of memory in the brain). Here, we review the current understanding of memory formation at a molecular and cellular level by focusing on insights provided using engram technology.
PDF
