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.
{"title":"Effects of maternal separation on punishment-driven risky decision making in adolescence and adulthood","authors":"Grace L. Minnes, Anna J. Wiener, Audrey S. Pisahl, Elizabeth A. Duecker, Boula A. Baskhairoun, Sharoderick C. Lowe, Nicholas W. Simon","doi":"10.1016/j.nlm.2024.108016","DOIUrl":"10.1016/j.nlm.2024.108016","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108016"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872700","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.2025.108020
Timothy J. Hill, Nathan M. Holmes, Kelly J. Clemens
Humans and animals use information about future access to rewards to influence their behaviour in the present, however the evidence for this is largely anecdotal. Here we use the nicotine intravenous self-administration paradigm to ask whether rats can use an auditory stimulus signalling a long (450 s) signalled time-out on the next trial to influence their nicotine intake in the present. Rats were trained to choose between low (15 µg/kg/infusion), medium (30 µg/kg/infusion) or high (60 µg/kg/infusion) doses of nicotine on any given trial. Trials either had a ‘light’ trial with no tone and a standard 20 s post-infusion time-out, a ‘short-tone’ trial where a tone was presented but the time-out remained at 20 s, or a ‘long-tone’ trial where a second tone played and was accompanied by a long 450 s time-out period. During training rats clearly showed that dose selection was based on both the dose on the previous trial and the latency between infusions. When tones were presented, rats shifted their preference from the low dose to the high dose when the long-delay tone was presented, and this choice was particularly pronounced when the rat had previously selected a low dose. Together these findings are the first evidence that rats can regulate their nicotine intake in the present in anticipation of a future non-drug period. This result is discussed with respect to theories of negative reinforcement.
{"title":"Male rats choose higher doses of nicotine in anticipation of a future non-drug period","authors":"Timothy J. Hill, Nathan M. Holmes, Kelly J. Clemens","doi":"10.1016/j.nlm.2025.108020","DOIUrl":"10.1016/j.nlm.2025.108020","url":null,"abstract":"<div><div>Humans and animals use information about future access to rewards to influence their behaviour in the present, however the evidence for this is largely anecdotal. Here we use the nicotine intravenous self-administration paradigm to ask whether rats can use an auditory stimulus signalling a long (450 s) signalled time-out on the next trial to influence their nicotine intake in the present. Rats were trained to choose between low (15 µg/kg/infusion), medium (30 µg/kg/infusion) or high (60 µg/kg/infusion) doses of nicotine on any given trial. Trials either had a ‘light’ trial with no tone and a standard 20 s post-infusion time-out, a ‘short-tone’ trial where a tone was presented but the time-out remained at 20 s, or a ‘long-tone’ trial where a second tone played and was accompanied by a long 450 s time-out period. During training rats clearly showed that dose selection was based on both the dose on the previous trial and the latency between infusions. When tones were presented, rats shifted their preference from the low dose to the high dose when the long-delay tone was presented, and this choice was particularly pronounced when the rat had previously selected a low dose. Together these findings are the first evidence that rats can regulate their nicotine intake in the present in anticipation of a future non-drug period. This result is discussed with respect to theories of negative reinforcement.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108020"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966126","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 : 2025-01-01DOI: 10.1016/j.nlm.2024.108015
Shoko Arai, Krzysztof A. Sypniewski, Constantine Pavlides
Episodic memory is subserved by interactions between entorhinal cortex (EC) and hippocampus. Within EC, a functional dissociation has been proposed for medial (MEC) and lateral (LEC) subregions, whereby, MEC processes spatial information while LEC processes information about objects and their location in space. Most of these studies, however, used classical methods which lack both spatial and temporal specificity, thus, the precise role of MEC/LEC in memory could use further clarification. First, we show a possible functional dissociation of MEC/LEC for place/object fear memory, by optogenetic suppression of these areas during memory acquisition. The main output of EC is to the hippocampus. MEC projects mainly towards proximal/superficial CA1 and deep CA3 while LEC towards distal/deep CA1 and superficial CA3. Dentate gyrus (DG), terminations of MEC/LEC are dissociated septotemporally. A functional dissociation has also been proposed for subregions of the hippocampus. Previous studies reported that proximal/distal CA1 process spatial/nonspatial information, respectively. For the second part of the study, we used the immediate-early gene Zif-268 to map neuronal activity in CA1. We first show enhanced Zif-268 expression and cluster-type organization in the proximal CA1 by place exposure and enhanced Zif-268 expression/cluster organization in distal CA1 following object exposure. Second, direct optogenetic stimulation of MEC/LEC, produced a similar enhancement/cluster-type organization in the same areas. Enhanced Zif-268 expression was also observed in CA3 and DG. These results substantiate previous findings and are proof positive that the hippocampus is organized in clusters to encode information generally ascribed to this structure.
{"title":"Differential roles of medial/lateral entorhinal cortex in spatial/object memory and contribution to hippocampal functional neuronal organization","authors":"Shoko Arai, Krzysztof A. Sypniewski, Constantine Pavlides","doi":"10.1016/j.nlm.2024.108015","DOIUrl":"10.1016/j.nlm.2024.108015","url":null,"abstract":"<div><div>Episodic memory is subserved by interactions between entorhinal cortex (EC) and hippocampus. Within EC, a functional dissociation has been proposed for medial (MEC) and lateral (LEC) subregions, whereby, MEC processes spatial information while LEC processes information about objects and their location in space. Most of these studies, however, used classical methods which lack both spatial and temporal specificity, thus, the precise role of MEC/LEC in memory could use further clarification. First, we show a possible functional dissociation of MEC/LEC for place/object fear memory, by optogenetic suppression of these areas during memory acquisition. The main output of EC is to the hippocampus. MEC projects mainly towards proximal/superficial CA1 and deep CA3 while LEC towards distal/deep CA1 and superficial CA3. Dentate gyrus (DG), terminations of MEC/LEC are dissociated septotemporally. A functional dissociation has also been proposed for subregions of the hippocampus. Previous studies reported that proximal/distal CA1 process spatial/nonspatial information, respectively. For the second part of the study, we used the immediate-early gene Zif-268 to map neuronal activity in CA1. We first show enhanced Zif-268 expression and cluster-type organization in the proximal CA1 by place exposure and enhanced Zif-268 expression/cluster organization in distal CA1 following object exposure. Second, direct optogenetic stimulation of MEC/LEC, produced a similar enhancement/cluster-type organization in the same areas. Enhanced Zif-268 expression was also observed in CA3 and DG. These results substantiate previous findings and are proof positive that the hippocampus is organized in clusters to encode information generally ascribed to this structure.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108015"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846744","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.2024.108017
Olivia S. O’Neill, Karley V. George, Emily P. Minard, Boyer D. Winters
Consolidated long-term memories can undergo strength or content modification via protein synthesis-dependent reconsolidation. This is the process by which a reminder cue initiates reactivation of the memory trace, triggering destabilization. Older and more strongly encoded spatial memories can resist destabilization due to biological boundary conditions. The present study investigated the role of dopamine (DA) at D1 receptors (D1Rs) in object location memory destabilization and overcoming boundary conditions for older (“remote”; tested with a 48-h rather than a 24-h delay between sample and reactivation) memory destabilization. Using male rats in a modified object location task, we found that administering the D1R antagonist SCH23390 (0.1 mg/kg, i.p.) prior to reactivation blocked destabilization of recently encoded memories, as well as novelty-induced destabilization of remote memories. Using remote parameters, systemically administered D1R agonist SKF38393 (5 mg/kg, i.p.) induced destabilization of remote object location memories in the absence of salient novelty. Intra-dorsal hippocampus administration of SCH23390 (2 μg/μL) also blocked destabilization of remote object location memories when a salient novel cue was present. These results are consistent with previous findings implicating DA in memory destabilization as well as demonstrate a role for D1-receptor activation in the destabilization of boundary condition protected-object location memories.
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