Bárður H Joensen, Marcus O Harrington, Sam C Berens, Scott A Cairney, M Gareth Gaskell, Aidan J Horner
{"title":"Targeted memory reactivation during sleep can induce forgetting of overlapping memories.","authors":"Bárður H Joensen, Marcus O Harrington, Sam C Berens, Scott A Cairney, M Gareth Gaskell, Aidan J Horner","doi":"10.1101/lm.053594.122","DOIUrl":"https://doi.org/10.1101/lm.053594.122","url":null,"abstract":"<p><p>Memory reactivation during sleep can shape new memories into a long-term form. Reactivation of memories can be induced via the delivery of auditory cues during sleep. Although this targeted memory reactivation (TMR) approach can strengthen newly acquired memories, research has tended to focus on single associative memories. It is less clear how TMR affects retention for overlapping associative memories. This is critical, given that repeated retrieval of overlapping associations during wake can lead to forgetting, a phenomenon known as retrieval-induced forgetting (RIF). We asked whether a similar pattern of forgetting occurs when TMR is used to cue reactivation of overlapping pairwise associations during sleep. Participants learned overlapping pairs-learned separately, interleaved with other unrelated pairs. During sleep, we cued a subset of overlapping pairs using TMR. While TMR increased retention for the first encoded pairs, memory decreased for the second encoded pairs. This pattern of retention was only present for pairs not tested prior to sleep. The results suggest that TMR can lead to forgetting, an effect similar to RIF during wake. However, this effect did not extend to memories that had been strengthened via retrieval prior to sleep. We therefore provide evidence for a reactivation-induced forgetting effect during sleep.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"401-411"},"PeriodicalIF":2.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40395893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Morgan E Bartholomew, Vincent Rozalski, Anne Richards, Joyce Gurdock, Mary Thornton, Connie Fee, Sa'ar L Lipshitz, Thomas J Metzler, Thomas C Neylan, Sabra S Inslicht
{"title":"Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD.","authors":"Morgan E Bartholomew, Vincent Rozalski, Anne Richards, Joyce Gurdock, Mary Thornton, Connie Fee, Sa'ar L Lipshitz, Thomas J Metzler, Thomas C Neylan, Sabra S Inslicht","doi":"10.1101/lm.053597.122","DOIUrl":"https://doi.org/10.1101/lm.053597.122","url":null,"abstract":"<p><p>Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"332-339"},"PeriodicalIF":2.0,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33493013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatial anxiety and self-confidence mediate sex/gender differences in mental rotation.","authors":"Linda Arrighi, Markus Hausmann","doi":"10.1101/lm.053596.122","DOIUrl":"https://doi.org/10.1101/lm.053596.122","url":null,"abstract":"<p><p>A recent meta-synthesis study with a sample of >12 million participants revealed that the male advantage in mental rotation (MR) is the largest cognitive sex/gender difference found in psychological literature. MR requires test takers to mentally rotate three-dimensional cubic figures under time restrictions. Previous studies have investigated how biological and social factors contribute to cognitive sex/gender differences in tasks of this type. Spatial anxiety and self-confidence in MR tasks have received less attention. The present study investigated the contribution of these psychological factors to sex/gender differences in MR performance. Participants (<i>n</i> = 269) completed two MR tasks that differed in task difficulty. Participants also indicated their self-confidence (for each item) and spatial anxiety. The results revealed that pronounced sex/gender differences in spatial anxiety and self-confidence mediate sex/gender in MR performance, especially when task demands are high. The current findings suggest that task-irrelevant factors that are not spatial cognitive in nature contribute largely to the well-known medium to large sex/gender differences in MR. Future studies should further explore mechanisms underlying cognitive sex/gender differences within a biopsychosocial approach.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"312-320"},"PeriodicalIF":2.0,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33493012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Persistent up-regulation of polyribosomes at synapses during long-term memory, reconsolidation, and extinction of associative memory.","authors":"Linnaea E Ostroff, Christopher K Cain","doi":"10.1101/lm.053577.122","DOIUrl":"https://doi.org/10.1101/lm.053577.122","url":null,"abstract":"<p><p>Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are resistant to protein synthesis inhibitors. We have previously reported that polyribosomes are up-regulated in the lateral amygdala (LA) during consolidation of aversive-cued Pavlovian conditioning. In this study, we used serial section electron microscopy reconstructions to determine whether the distribution of dendritic polyribosomes returns to baseline during the long-term memory phase. Relative to control groups, long-term memory was associated with up-regulation of polyribosomes throughout dendrites, including in dendritic spines of all sizes. Retrieval of a consolidated memory by presentation of a small number of cues induces a new, transient requirement for protein synthesis to maintain the memory, while presentation of a large number of cues results in extinction learning, forming a new memory. One hour after retrieval or extinction training, the distribution of dendritic polyribosomes was similar except in the smallest spines, which had more polyribosomes in the extinction group. Our results demonstrate that the effects of learning on dendritic polyribosomes are not restricted to the transient translation-dependent phase of memory formation. Cued Pavlovian conditioning induces persistent synapse strengthening in the LA that is not reversed by retrieval or extinction, and dendritic polyribosomes may therefore correlate generally with synapse strength as opposed to recent activity or transient translational processes.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"192-202"},"PeriodicalIF":2.0,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40625539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Developmental emergence of persistent memory for contextual and auditory fear in mice.","authors":"Rojina Samifanni, Mudi Zhao, Arely Cruz-Sanchez, Agarsh Satheesh, Unza Mumtaz, Maithe Arruda-Carvalho","doi":"10.1101/lm.053471.121","DOIUrl":"https://doi.org/10.1101/lm.053471.121","url":null,"abstract":"<p><p>The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning tasks, contextual and auditory fear, share the same time line of developmental onset. Here, we compared the ontogeny of remote contextual and auditory fear in C57BL/6J mice across early life. Mice at postnatal day (P)15, 21, 25, 28, and 30 underwent either contextual or auditory fear training and were tested for fear retrieval 1 or 30 d later. We found that mice displayed 30-d memory for context- and tone-fear starting at P25. We did not find sex differences in the ontogeny of either type of fear memory. Furthermore, 30-d contextual fear retrieval led to an increase in the number of c-Fos positive cells in the prelimbic region of the prefrontal cortex only at an age in which the contextual fear memory was successfully retrieved. These data delineate a precise time line for the emergence of persistent contextual and auditory fear memories in mice and suggest that the prelimbic cortex is only recruited for remote memory recall upon the onset of memory persistence.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"414-421"},"PeriodicalIF":2.0,"publicationDate":"2021-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/90/LM053471Sam.PMC8525421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39531792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Excitatory postsynaptic calcium transients at <i>Aplysia</i> sensory-motor neuron synapses allow for quantal examination of synaptic strength over multiple days in culture.","authors":"Tyler W Dunn, Wayne S Sossin","doi":"10.1101/lm.052639.120","DOIUrl":"https://doi.org/10.1101/lm.052639.120","url":null,"abstract":"<p><p>A more thorough description of the changes in synaptic strength underlying synaptic plasticity may be achieved with quantal resolution measurements at individual synaptic sites. Here, we demonstrate that by using a membrane targeted genetic calcium sensor, we can measure quantal synaptic events at the individual synaptic sites of <i>Aplysia</i> sensory neuron to motor neuron synaptic connections. These results show that synaptic strength is not evenly distributed between all contacts in these cultures, but dominated by multiquantal sites of synaptic contact, likely clusters of individual synaptic sites. Surprisingly, most synaptic contacts were not found opposite presynaptic varicosities, but instead at areas of pre- and postsynaptic contact with no visible thickening of membranes. The release probability, quantal size, and quantal content can be measured over days at individual synaptic contacts using this technique. Homosynaptic depression was accompanied by a reduction in release site probability, with no evidence of individual synaptic site silencing over the course of depression. This technique shows promise in being able to address outstanding questions in this system, including determining the synaptic changes that maintain long-term alterations in synaptic strength that underlie memory.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"277-290"},"PeriodicalIF":2.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/5d/LM052639Dun.PMC8372562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39317539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reto Bisaz, Benjamin Bessières, Janelle M Miranda, Alessio Travaglia, Cristina M Alberini
{"title":"Recovery of memory from infantile amnesia is developmentally constrained.","authors":"Reto Bisaz, Benjamin Bessières, Janelle M Miranda, Alessio Travaglia, Cristina M Alberini","doi":"10.1101/lm.052621.120","DOIUrl":"https://doi.org/10.1101/lm.052621.120","url":null,"abstract":"<p><p>Episodic memories formed during infancy are rapidly forgotten, a phenomenon associated with infantile amnesia, the inability of adults to recall early-life memories. In both rats and mice, infantile memories, although not expressed, are actually stored long term in a latent form. These latent memories can be reinstated later in life by certain behavioral reminders or by artificial reactivations of neuronal ensembles activated at training. Whether the recovery of infantile memories is limited by developmental age, maternal presence, or contingency of stimuli presentation remains to be determined. Here, we show that the return of inhibitory avoidance memory in rats following a behavioral reactivation consisting of an exposure to the context (conditioned stimuli [CS]) and footshock (unconditioned stimuli [US]) given in a temporally unpaired fashion, is evident immediately after US and is limited by the developmental age at which the reactivations are presented; however, it is not influenced by maternal presence or the time interval between training and reactivation. We conclude that one limiting factor for infantile memory reinstatement is developmental age, suggesting that a brain maturation process is necessary to allow the recovery of a \"lost\" infantile memory.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"300-306"},"PeriodicalIF":2.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/73/LM052621Bis.PMC8372561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39317542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Yokose, William D Marks, Naoki Yamamoto, Sachie K Ogawa, Takashi Kitamura
{"title":"Entorhinal cortical Island cells regulate temporal association learning with long trace period.","authors":"Jun Yokose, William D Marks, Naoki Yamamoto, Sachie K Ogawa, Takashi Kitamura","doi":"10.1101/lm.052589.120","DOIUrl":"https://doi.org/10.1101/lm.052589.120","url":null,"abstract":"<p><p>Temporal association learning (TAL) allows for the linkage of distinct, nonsynchronous events across a period of time. This function is driven by neural interactions in the entorhinal cortical-hippocampal network, especially the neural input from the pyramidal cells in layer III of medial entorhinal cortex (MECIII) to hippocampal CA1 is crucial for TAL. Successful TAL depends on the strength of event stimuli and the duration of the temporal gap between events. Whereas it has been demonstrated that the neural input from pyramidal cells in layer II of MEC, referred to as Island cells, to inhibitory neurons in dorsal hippocampal CA1 controls TAL when the strength of event stimuli is weak, it remains unknown whether Island cells regulate TAL with long trace periods as well. To understand the role of Island cells in regulating the duration of the learnable trace period in TAL, we used Pavlovian trace fear conditioning (TFC) with a 60-sec long trace period (long trace fear conditioning [L-TFC]) coupled with optogenetic and chemogenetic neural activity manipulations as well as cell type-specific neural ablation. We found that ablation of Island cells in MECII partially increases L-TFC performance. Chemogenetic manipulation of Island cells causes differential effectiveness in Island cell activity and leads to a circuit imbalance that disrupts L-TFC. However, optogenetic terminal inhibition of Island cell input to dorsal hippocampal CA1 during the temporal association period allows for long trace intervals to be learned in TFC. These results demonstrate that Island cells have a critical role in regulating the duration of time bridgeable between associated events in TAL.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"319-328"},"PeriodicalIF":2.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/d6/LM052589Yok.PMC8372565.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39317544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tony J Cunningham, Ryan Bottary, Dan Denis, Jessica D Payne
{"title":"Sleep spectral power correlates of prospective memory maintenance.","authors":"Tony J Cunningham, Ryan Bottary, Dan Denis, Jessica D Payne","doi":"10.1101/lm.053412.121","DOIUrl":"https://doi.org/10.1101/lm.053412.121","url":null,"abstract":"<p><p>Prospective memory involves setting an intention to act that is maintained over time and executed when appropriate. Slow wave sleep (SWS) has been implicated in maintaining prospective memories, although which SWS oscillations most benefit this memory type remains unclear. Here, we investigated SWS spectral power correlates of prospective memory. Healthy young adult participants completed three ongoing tasks in the morning or evening. They were then given the prospective memory instruction to remember to press \"Q\" when viewing the words \"horse\" or \"table\" when repeating the ongoing task after a 12-h delay including overnight, polysomnographically recorded sleep or continued daytime wakefulness. Spectral power analysis was performed on recorded sleep EEG. Two additional groups were tested in the morning or evening only, serving as time-of-day controls. Participants who slept demonstrated superior prospective memory compared with those who remained awake, an effect not attributable to time-of-day of testing. Contrary to prior work, prospective memory was negatively associated with SWS. Furthermore, significant increases in spectral power in the delta-theta frequency range (1.56 Hz-6.84 Hz) during SWS was observed in participants who failed to execute the prospective memory instructions. Although sleep benefits prospective memory maintenance, this benefit may be compromised if SWS is enriched with delta-theta activity.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"291-299"},"PeriodicalIF":2.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/9f/LM053412Cun.PMC8372568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39317541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}