Pub Date : 2025-03-01DOI: 10.1016/j.nlm.2025.108037
Benita Jin , Michael W. Gongwer , Laura A. DeNardo
Memory retrieval involves coordinated activity across multiple brain regions. Yet how the organization of memory networks evolves throughout development remains poorly understood. In this study, we compared whole-brain functional networks that are active during contextual fear memory recall in infant, juvenile, and adult mice. Our analyses revealed that long-term memory networks change significantly across postnatal development. Infant fear memory networks are dense and heterogeneous, whereas adult networks are sparse and have a small-world topology. While hippocampal subregions were highly connected nodes at all ages, the cortex gained many functional connections across development. Different functional connections matured at different rates, but their developmental timing fell into three major categories: stepwise change between two ages, linear change across all ages, or inverted-U, with elevated functional connectivity in juveniles. Our work highlights how a subset of brain regions likely maintain important roles in fear memory encoding, but the functional connectivity of fear memory networks undergoes significant reorganization across development. Together, these results provide a blueprint for studying how correlated cellular activity in key areas distinctly regulates memory storage and retrieval across development.
记忆检索涉及多个大脑区域的协调活动。然而，人们对记忆网络的组织在整个发育过程中是如何演变的仍然知之甚少。在这项研究中，我们比较了婴儿、幼年和成年小鼠在回忆情境恐惧记忆时活跃的全脑功能网络。我们的分析表明，长期记忆网络在出生后的发育过程中发生了显著变化。婴儿期的恐惧记忆网络密集且异构，而成年期的网络则稀疏且具有小世界拓扑结构。虽然海马亚区在所有年龄段都是高度连接的节点，但皮层在整个发育过程中获得了许多功能连接。不同的功能连接以不同的速度成熟，但其发育时间可分为三大类：两个年龄段之间的阶梯式变化、所有年龄段的线性变化或倒 U 型变化，其中少年期的功能连接性较高。我们的研究突出表明，一部分大脑区域可能在恐惧记忆编码中保持重要作用，但恐惧记忆网络的功能连接性在整个发育过程中经历了重大重组。这些结果为研究关键区域的相关细胞活动如何在整个发育过程中对记忆存储和检索进行独特调节提供了蓝图。
{"title":"Developmental changes in brain-wide fear memory networks","authors":"Benita Jin , Michael W. Gongwer , Laura A. DeNardo","doi":"10.1016/j.nlm.2025.108037","DOIUrl":"10.1016/j.nlm.2025.108037","url":null,"abstract":"<div><div>Memory retrieval involves coordinated activity across multiple brain regions. Yet how the organization of memory networks evolves throughout development remains poorly understood. In this study, we compared whole-brain functional networks that are active during contextual fear memory recall in infant, juvenile, and adult mice. Our analyses revealed that long-term memory networks change significantly across postnatal development. Infant fear memory networks are dense and heterogeneous, whereas adult networks are sparse and have a small-world topology. While hippocampal subregions were highly connected nodes at all ages, the cortex gained many functional connections across development. Different functional connections matured at different rates, but their developmental timing fell into three major categories: stepwise change between two ages, linear change across all ages, or inverted-U, with elevated functional connectivity in juveniles. Our work highlights how a subset of brain regions likely maintain important roles in fear memory encoding, but the functional connectivity of fear memory networks undergoes significant reorganization across development. Together, these results provide a blueprint for studying how correlated cellular activity in key areas distinctly regulates memory storage and retrieval across development.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108037"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.nlm.2025.108038
Dahae J. Jun, Rebecca Shannon, Katherine Tschida, David M. Smith
The medial prefrontal cortex (mPFC) plays a key role in memory and behavioral flexibility, and a growing body of evidence suggests that the prelimbic (PL) and infralimbic (IL) subregions contribute differently to these processes. Studies of fear conditioning and goal-directed learning suggest that the PL promotes behavioral responses and memory retrieval, while the IL inhibits them. Other studies have shown that the mPFC is engaged under conditions of high interference. This raises the possibility that the PL and IL play differing roles in resolving interference. To examine this, we first used chemogenetics (DREADDs) to suppress mPFC neuronal activity and tested subjects on a conditional discrimination task known to be sensitive to muscimol inactivation. After confirming the effectiveness of the DREADD procedures, we conducted a second experiment to examine the PL and IL roles in a high interference memory task. We trained rats on two consecutive sets of conflicting odor discrimination problems, A and B, followed by test sessions involving a mid-session switch between the problem sets. Controls repeatedly performed worse on Set A, suggesting that learning Set B inhibited the rats’ ability to retrieve Set A memories (i.e. retroactive interference). PL inactivation rats performed similarly to controls. However, IL inactivation rats did not show this effect, suggesting that the IL plays a critical role in suppressing the retrieval of previously acquired memories that may interfere with retrieval of more recent memories. These results suggest that the IL plays a critical role in memory control processes needed for resolving interference.
{"title":"The infralimbic, but not the prelimbic cortex is needed for a complex olfactory memory task","authors":"Dahae J. Jun, Rebecca Shannon, Katherine Tschida, David M. Smith","doi":"10.1016/j.nlm.2025.108038","DOIUrl":"10.1016/j.nlm.2025.108038","url":null,"abstract":"<div><div>The medial prefrontal cortex (mPFC) plays a key role in memory and behavioral flexibility, and a growing body of evidence suggests that the prelimbic (PL) and infralimbic (IL) subregions contribute differently to these processes. Studies of fear conditioning and goal-directed learning suggest that the PL promotes behavioral responses and memory retrieval, while the IL inhibits them. Other studies have shown that the mPFC is engaged under conditions of high interference. This raises the possibility that the PL and IL play differing roles in resolving interference. To examine this, we first used chemogenetics (DREADDs) to suppress mPFC neuronal activity and tested subjects on a conditional discrimination task known to be sensitive to muscimol inactivation. After confirming the effectiveness of the DREADD procedures, we conducted a second experiment to examine the PL and IL roles in a high interference memory task. We trained rats on two consecutive sets of conflicting odor discrimination problems, A and B, followed by test sessions involving a mid-session switch between the problem sets. Controls repeatedly performed worse on Set A, suggesting that learning Set B inhibited the rats’ ability to retrieve Set A memories (i.e. retroactive interference). PL inactivation rats performed similarly to controls. However, IL inactivation rats did not show this effect, suggesting that the IL plays a critical role in suppressing the retrieval of previously acquired memories that may interfere with retrieval of more recent memories. These results suggest that the IL plays a critical role in memory control processes needed for resolving interference.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108038"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.nlm.2025.108036
Greta Leonore Balmer , Shuvrangshu Guha , Stefanie Poll
Memories are our reservoir of knowledge and thus, are crucial for guiding decisions and defining our self. The physical correlate of a memory in the brain is termed an engram and since decades helps researchers to elucidate the intricate nature of our imprinted experiences and knowledge. Given the importance that memories have for our lives, their impairment can present a tremendous burden. In this review we aim to discuss engram malfunctioning across diseases, covering dementia-associated pathologies, epilepsy, chronic pain and psychiatric disorders. Current neuroscientific tools allow to witness the emergence and fate of engram cells and enable their manipulation. We further suggest that specific mechanisms of mnemonic malfunction can be derived from engram cell readouts. While depicting the way diseases act on the mnemonic component – specifically, on the cellular engram – we emphasize a differentiation between forms of amnesia and hypermnesia. Finally, we highlight commonalities and distinctions of engram impairments on the cellular level across diseases independent of their pathogenic origins and discuss prospective therapeutic measures.
{"title":"Engrams across diseases: Different pathologies – unifying mechanisms?","authors":"Greta Leonore Balmer , Shuvrangshu Guha , Stefanie Poll","doi":"10.1016/j.nlm.2025.108036","DOIUrl":"10.1016/j.nlm.2025.108036","url":null,"abstract":"<div><div>Memories are our reservoir of knowledge and thus, are crucial for guiding decisions and defining our self. The physical correlate of a memory in the brain is termed an engram and since decades helps researchers to elucidate the intricate nature of our imprinted experiences and knowledge. Given the importance that memories have for our lives, their impairment can present a tremendous burden. In this review we aim to discuss engram malfunctioning across diseases, covering dementia-associated pathologies, epilepsy, chronic pain and psychiatric disorders. Current neuroscientific tools allow to witness the emergence and fate of engram cells and enable their manipulation. We further suggest that specific mechanisms of mnemonic malfunction can be derived from engram cell readouts. While depicting the way diseases act on the mnemonic component – specifically, on the cellular engram – we emphasize a differentiation between forms of amnesia and hypermnesia. Finally, we highlight commonalities and distinctions of engram impairments on the cellular level across diseases independent of their pathogenic origins and discuss prospective therapeutic measures.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108036"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.nlm.2025.108035
Hisayuki Osanai , Mary Arai , Takashi Kitamura , Sachie K. Ogawa
Although many methods for automated fluorescent-labeled cell detection have been proposed, not all of them assume a highly inhomogeneous background arising from complex biological structures. Here, we propose an automated cell detection algorithm that accounts for and subtracts the inhomogeneous background by avoiding high-intensity pixels in the blur filtering calculation. Cells were detected by intensity thresholding in the background-subtracted image, and the algorithm’s performance was tested on NeuN- and c-Fos-stained images in the mouse prefrontal cortex and hippocampal dentate gyrus. In addition, applications in c-Fos positive cell counting and the quantification for the expression level in double-labeled cells were demonstrated. Our method of automated detection after background assumption (ADABA) offers the advantage of high-throughput and unbiased analysis in regions with complex biological structures that produce inhomogeneous background.
{"title":"Automated detection of c-Fos-expressing neurons using inhomogeneous background subtraction in fluorescent images","authors":"Hisayuki Osanai , Mary Arai , Takashi Kitamura , Sachie K. Ogawa","doi":"10.1016/j.nlm.2025.108035","DOIUrl":"10.1016/j.nlm.2025.108035","url":null,"abstract":"<div><div>Although many methods for automated fluorescent-labeled cell detection have been proposed, not all of them assume a highly inhomogeneous background arising from complex biological structures. Here, we propose an automated cell detection algorithm that accounts for and subtracts the inhomogeneous background by avoiding high-intensity pixels in the blur filtering calculation. Cells were detected by intensity thresholding in the background-subtracted image, and the algorithm’s performance was tested on NeuN- and c-Fos-stained images in the mouse prefrontal cortex and hippocampal dentate gyrus. In addition, applications in c-Fos positive cell counting and the quantification for the expression level in double-labeled cells were demonstrated. Our method of automated detection after background assumption (ADABA) offers the advantage of high-throughput and unbiased analysis in regions with complex biological structures that produce inhomogeneous background.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108035"},"PeriodicalIF":2.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.nlm.2025.108034
Xuefeng Yang , Xiu Miao , Franziska Schweiggart , Sophia Großmann , Karsten Rauss , Manfred Hallschmid , Jan Born , Nicolas D. Lutz
The consolidation of long-term memory is thought to critically rely on sleep. However, first evidence from a study in Drosophila suggests that hunger, as another brain state, can benefit memory consolidation as well. Here, we report two human (within-subjects crossover) experiments examining the effects of fasting (versus satiated conditions) during a 10-hour post-encoding consolidation period on subsequent recall of declarative and procedural memories in healthy men. In Experiment 1, participants (n = 16), after an 18.5-hour fasting period, encoded 3 memory tasks (word paired associates, a visual version of the Deese-Roediger-McDermott task, finger tapping) and subsequently either continued to fast or received standardized meals. Recall was tested 48 h later in a satiated state. Experiment 2 (n = 16 participants) differed from Experiment 1 in that a What-Where-When episodic memory task replaced the Deese-Roediger-McDermott task and recall was tested only 24 h later in a fasted state. Compared with the satiated state, fasting enhanced cued recall of word paired associates (more correct and faster responses) and item recognition in the What-Where-When task. By contrast, fasting impaired recall of episodic context memory, i.e., spatial context in the Deese-Roediger-McDermott task, and temporal-spatial context in the What-Where-When task. Procedural memory (finger tapping) remained unaffected. This pattern suggests a differential effect of fasting selectively promoting consolidation of semantic-like representations in cortical networks whereas hippocampal representations of episodic context are weakened. We speculate that hunger strengthens cortical representations by suppressing hippocampal interference during wake consolidation. Yet, the underlying mechanism remains to be clarified.
{"title":"The effect of fasting on human memory consolidation","authors":"Xuefeng Yang , Xiu Miao , Franziska Schweiggart , Sophia Großmann , Karsten Rauss , Manfred Hallschmid , Jan Born , Nicolas D. Lutz","doi":"10.1016/j.nlm.2025.108034","DOIUrl":"10.1016/j.nlm.2025.108034","url":null,"abstract":"<div><div>The consolidation of long-term memory is thought to critically rely on sleep. However, first evidence from a study in <em>Drosophila</em> suggests that hunger, as another brain state, can benefit memory consolidation as well. Here, we report two human (within-subjects crossover) experiments examining the effects of fasting (versus satiated conditions) during a 10-hour post-encoding consolidation period on subsequent recall of declarative and procedural memories in healthy men. In Experiment 1, participants (n = 16), after an 18.5-hour fasting period, encoded 3 memory tasks (word paired associates, a visual version of the Deese-Roediger-McDermott task, finger tapping) and subsequently either continued to fast or received standardized meals. Recall was tested 48 h later in a satiated state. Experiment 2 (n = 16 participants) differed from Experiment 1 in that a What-Where-When episodic memory task replaced the Deese-Roediger-McDermott task and recall was tested only 24 h later in a fasted state. Compared with the satiated state, fasting enhanced cued recall of word paired associates (more correct and faster responses) and item recognition in the What-Where-When task. By contrast, fasting impaired recall of episodic context memory, i.e., spatial context in the Deese-Roediger-McDermott task, and temporal-spatial context in the What-Where-When task. Procedural memory (finger tapping) remained unaffected. This pattern suggests a differential effect of fasting selectively promoting consolidation of semantic-like representations in cortical networks whereas hippocampal representations of episodic context are weakened. We speculate that hunger strengthens cortical representations by suppressing hippocampal interference during wake consolidation. Yet, the underlying mechanism remains to be clarified.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108034"},"PeriodicalIF":2.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.nlm.2025.108031
Thije S. Willems , Hui Xiong , Helmut W. Kessels , Sylvie L. Lesuis
Memory formation depends on the selective recruitment of neuronal ensembles into circuits known as engrams, which represent the physical substrate of memory. Sparse encoding of these ensembles is essential for memory specificity and efficiency. AMPA receptor (AMPAR) subunits, particularly GluA1, play a central role in synaptic plasticity, which underpins memory encoding. This study investigates how GluA1 expression influences the recruitment of neurons into memory engrams. Using global GluA1 knockout (GluA1KO) mice, localized knockout models, and contextual fear-conditioning paradigms, we evaluated the role of GluA1 in memory formation and engram sparsity.
GluA1KO mice exhibited impaired short-term memory retention but preserved 24-hour contextual memory. Despite this, these mice displayed increased expression of the immediate early gene Arc in hippocampal neurons, indicative of a denser engram network. Electrophysiological analyses revealed reduced synaptic strength in GluA1-deficient neurons, irrespective of Arc expression. Localized GluA1 knockout in the hippocampus confirmed that GluA1 deficiency increases neuronal recruitment into engrams, disrupting the sparse encoding typically observed in wild-type mice.
These findings demonstrate that GluA1-containing AMPARs constrain engram size, ensuring selective recruitment of neurons for efficient memory encoding. By regulating synaptic plasticity, GluA1 facilitates both the encoding and size of memory circuits. This study highlights the critical role of GluA1 in maintaining sparse engram formation and provides insight into mechanisms underlying memory deficits in conditions where synaptic composition is altered.
{"title":"GluA1-containing AMPA receptors are necessary for sparse memory engram formation","authors":"Thije S. Willems , Hui Xiong , Helmut W. Kessels , Sylvie L. Lesuis","doi":"10.1016/j.nlm.2025.108031","DOIUrl":"10.1016/j.nlm.2025.108031","url":null,"abstract":"<div><div>Memory formation depends on the selective recruitment of neuronal ensembles into circuits known as engrams, which represent the physical substrate of memory. Sparse encoding of these ensembles is essential for memory specificity and efficiency. AMPA receptor (AMPAR) subunits, particularly GluA1, play a central role in synaptic plasticity, which underpins memory encoding. This study investigates how GluA1 expression influences the recruitment of neurons into memory engrams. Using global GluA1 knockout (GluA1<sup>KO</sup>) mice, localized knockout models, and contextual fear-conditioning paradigms, we evaluated the role of GluA1 in memory formation and engram sparsity.</div><div>GluA1<sup>KO</sup> mice exhibited impaired short-term memory retention but preserved 24-hour contextual memory. Despite this, these mice displayed increased expression of the immediate early gene Arc in hippocampal neurons, indicative of a denser engram network. Electrophysiological analyses revealed reduced synaptic strength in GluA1-deficient neurons, irrespective of Arc expression. Localized GluA1 knockout in the hippocampus confirmed that GluA1 deficiency increases neuronal recruitment into engrams, disrupting the sparse encoding typically observed in wild-type mice.</div><div>These findings demonstrate that GluA1-containing AMPARs constrain engram size, ensuring selective recruitment of neurons for efficient memory encoding. By regulating synaptic plasticity, GluA1 facilitates both the encoding and size of memory circuits. This study highlights the critical role of GluA1 in maintaining sparse engram formation and provides insight into mechanisms underlying memory deficits in conditions where synaptic composition is altered.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108031"},"PeriodicalIF":2.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.nlm.2025.108033
Panthea Nemat, Salimat Semenova, Rolinka J. van der Loo, August B. Smit, Sabine Spijker, Michel C. van den Oever, Priyanka Rao-Ruiz
Learning enhances hippocampal engram cell synaptic connectivity which is crucial for engram reactivation and recall to natural cues. Memory retrieval engages only a subset of the learning-activated ensemble, indicating potential differences in synaptic connectivity signatures of reactivated and non-reactivated cells. We probed these differences in structural synaptic connectivity patterns after recent memory retrieval, 72 h after either neutral Context Exploration (CE) or aversive Contextual Fear Conditioning (CFC). Using a combination of eGRASP (enhanced green fluorescent protein (GFP) reconstitution across synaptic partners) and viral-TRAP (targeted recombination in activated populations) to label CA3 synapses onto CA1 engram cells, we investigated differences in spine density, clusters, and morphology between the reactivated and non-reactivated population of the learning ensemble. In doing so, we developed a pipeline for reconstruction and analysis of dendrites and spines, taking nested data structure into account. Our data demonstrate an interplay between reactivation status, context valence or both factors on the number, distribution, and morphology of CA1 engram cell synapses. Despite a lack of differences in spine density, reactivated engram cells encoding an aversive context were characterised by a higher probability of forming spine clusters and a more dynamic spine type signature compared to their non-reactivated counterparts or engram cells encoding a neutral context. Together, our data indicate that the learning-activated ensemble undergoes different trajectories in structural synaptic connectivity during engram refinement.
{"title":"Structural synaptic signatures of contextual memory retrieval-reactivated hippocampal engram cells","authors":"Panthea Nemat, Salimat Semenova, Rolinka J. van der Loo, August B. Smit, Sabine Spijker, Michel C. van den Oever, Priyanka Rao-Ruiz","doi":"10.1016/j.nlm.2025.108033","DOIUrl":"10.1016/j.nlm.2025.108033","url":null,"abstract":"<div><div>Learning enhances hippocampal engram cell synaptic connectivity which is crucial for engram reactivation and recall to natural cues. Memory retrieval engages only a subset of the learning-activated ensemble, indicating potential differences in synaptic connectivity signatures of reactivated and non-reactivated cells. We probed these differences in structural synaptic connectivity patterns after recent memory retrieval, 72 h after either neutral Context Exploration (CE) or aversive Contextual Fear Conditioning (CFC). Using a combination of eGRASP (enhanced green fluorescent protein (GFP) reconstitution across synaptic partners) and viral-TRAP (targeted recombination in activated populations) to label CA3 synapses onto CA1 engram cells, we investigated differences in spine density, clusters, and morphology between the reactivated and non-reactivated population of the learning ensemble. In doing so, we developed a pipeline for reconstruction and analysis of dendrites and spines, taking nested data structure into account. Our data demonstrate an interplay between reactivation status, context valence or both factors on the number, distribution, and morphology of CA1 engram cell synapses. Despite a lack of differences in spine density, reactivated engram cells encoding an aversive context were characterised by a higher probability of forming spine clusters and a more dynamic spine type signature compared to their non-reactivated counterparts or engram cells encoding a neutral context. Together, our data indicate that the learning-activated ensemble undergoes different trajectories in structural synaptic connectivity during engram refinement.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108033"},"PeriodicalIF":2.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.nlm.2025.108032
Alessandra Franceschini , Michelle Jin , Claire W. Chen , Ludovico Silvestri , Alessia Mastrodonato , Christine Ann Denny
In recent years, there has been significant progress in memory research, driven by genetic and imaging technological advances that have given unprecedented access to individual memory traces or engrams. Although Karl Lashley argued since the 1930s that an engram is not confined to a particular area but rather distributed across the entire brain, most current studies have focused exclusively on a single or few brain regions. However, this compartmentalized approach overlooks the interactions between multiple brain regions, limiting our understanding of engram mechanisms. More recently, several studies have begun to investigate engrams across the brain, but research is still limited by a lack of standardized techniques capable of reconstructing multiple ensembles at single-cell resolution across the entire brain. In this review, we guide researchers through the latest technological advancements and discoveries in immediate early gene (IEG) techniques, tissue clearing methods, microscope modalities, and automated large-scale analysis. These innovations could propel the field forward in building brain-wide engram maps of normal and disease states, thus, providing unprecedented new insights. Ultimately, this review aims to bridge the gap between research focused on single brain regions and the need for a comprehensive understanding of whole-brain engrams, revealing new approaches for exploring the neuronal mechanisms underlying engrams.
{"title":"Brain-wide immunolabeling and tissue clearing applications for engram research","authors":"Alessandra Franceschini , Michelle Jin , Claire W. Chen , Ludovico Silvestri , Alessia Mastrodonato , Christine Ann Denny","doi":"10.1016/j.nlm.2025.108032","DOIUrl":"10.1016/j.nlm.2025.108032","url":null,"abstract":"<div><div>In recent years, there has been significant progress in memory research, driven by genetic and imaging technological advances that have given unprecedented access to individual memory traces or engrams. Although Karl Lashley argued since the 1930s that an engram is not confined to a particular area but rather distributed across the entire brain, most current studies have focused exclusively on a single or few brain regions. However, this compartmentalized approach overlooks the interactions between multiple brain regions, limiting our understanding of engram mechanisms. More recently, several studies have begun to investigate engrams across the brain, but research is still limited by a lack of standardized techniques capable of reconstructing multiple ensembles at single-cell resolution across the entire brain. In this review, we guide researchers through the latest technological advancements and discoveries in immediate early gene (IEG) techniques, tissue clearing methods, microscope modalities, and automated large-scale analysis. These innovations could propel the field forward in building brain-wide engram maps of normal and disease states, thus, providing unprecedented new insights. Ultimately, this review aims to bridge the gap between research focused on single brain regions and the need for a comprehensive understanding of whole-brain engrams, revealing new approaches for exploring the neuronal mechanisms underlying engrams.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108032"},"PeriodicalIF":2.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.nlm.2025.108021
Guillem R. Esber, Geoffrey Schoenbaum, Mihaela D. Iordanova
{"title":"The Rescorla-Wagner model: It is not what you think it is","authors":"Guillem R. Esber, Geoffrey Schoenbaum, Mihaela D. Iordanova","doi":"10.1016/j.nlm.2025.108021","DOIUrl":"10.1016/j.nlm.2025.108021","url":null,"abstract":"","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108021"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.nlm.2024.108016
Grace L. Minnes, Anna J. Wiener, Audrey S. Pisahl, Elizabeth A. Duecker, Boula A. Baskhairoun, Sharoderick C. Lowe, Nicholas W. Simon
Early life adversity (ELA) is associated with a multitude of neural and behavioral aberrations. To develop treatments to mitigate the effects of ELA, it is critical to determine which aspects of cognition are affected and when these disturbances manifest across the lifespan. Here, we tested the effects of maternal separation, an established rodent model of ELA, on punishment-driven risky decision-making longitudinally in both adolescence (25–55 days old) and adulthood (80–100 days old). Risk-taking was assessed with the Risky Decision-making Task, wherein rats choose between a small, safe reward and a large reward accompanied by an escalating risk of punishment (foot shock). We observed that rats exposed to maternal separation were more prone to risk-taking than controls during adolescence, and demonstrated reduced latency to make both risky and safe decisions. Interestingly, this augmented risk-taking was no longer evident in adulthood. Males and females displayed comparable levels of risk-taking during adolescence then diverged in adulthood, with adult males displaying a sharp increase in risk-taking. Finally, we observed that risk-taking changed across the lifespan in rats exposed to maternal separation, but not in control rats. Collectively, these data reveal that ELA engenders risk-taking in adolescence but not adulthood, and that sex differences in risky decision-making are not evident until adulthood. This has important implications for the development of both behavioral and biological treatments to improve decision-making during the vulnerable adolescent period.
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