Brain and neuroscience advances最新文献

{"title":"Reinforcement learning approaches to hippocampus-dependent flexible spatial navigation","authors":"Charline Tessereau, R. O’Dea, S. Coombes, T. Bast","doi":"10.1101/2020.07.30.229005","DOIUrl":"https://doi.org/10.1101/2020.07.30.229005","url":null,"abstract":"Humans and non-human animals show great flexibility in spatial navigation, including the ability to return to specific locations based on as few as one single experience. To study spatial navigation in the laboratory, watermaze tasks, in which rats have to find a hidden platform in a pool of cloudy water surrounded by spatial cues, have long been used. Analogous tasks have been developed for human participants using virtual environments. Spatial learning in the watermaze is facilitated by the hippocampus. In particular, rapid, one-trial, allocentric place learning, as measured in the delayed-matching-to-place variant of the watermaze task, which requires rodents to learn repeatedly new locations in a familiar environment, is hippocampal dependent. In this article, we review some computational principles, embedded within a reinforcement learning framework, that utilise hippocampal spatial representations for navigation in watermaze tasks. We consider which key elements underlie their efficacy, and discuss their limitations in accounting for hippocampus-dependent navigation, both in terms of behavioural performance (i.e. how well do they reproduce behavioural measures of rapid place learning) and neurobiological realism (i.e. how well do they map to neurobiological substrates involved in rapid place learning). We discuss how an actor–critic architecture, enabling simultaneous assessment of the value of the current location and of the optimal direction to follow, can reproduce one-trial place learning performance as shown on watermaze and virtual delayed-matching-to-place tasks by rats and humans, respectively, if complemented with map-like place representations. The contribution of actor–critic mechanisms to delayed-matching-to-place performance is consistent with neurobiological findings implicating the striatum and hippocampo-striatal interaction in delayed-matching-to-place performance, given that the striatum has been associated with actor–critic mechanisms. Moreover, we illustrate that hierarchical computations embedded within an actor–critic architecture may help to account for aspects of flexible spatial navigation. The hierarchical reinforcement learning approach separates trajectory control via a temporal-difference error from goal selection via a goal prediction error and may account for flexible, trial-specific, navigation to familiar goal locations, as required in some arm-maze place memory tasks, although it does not capture one-trial learning of new goal locations, as observed in open field, including watermaze and virtual, delayed-matching-to-place tasks. Future models of one-shot learning of new goal locations, as observed on delayed-matching-to-place tasks, should incorporate hippocampal plasticity mechanisms that integrate new goal information with allocentric place representation, as such mechanisms are supported by substantial empirical evidence.","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45134498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventral midline thalamus is not necessary for systemic consolidation of a social memory in the rat.","authors":"Etienne Quet,&nbsp;Jean-Christophe Cassel,&nbsp;Brigitte Cosquer,&nbsp;Marine Galloux,&nbsp;Anne Pereira De Vasconcelos,&nbsp;Aline Stéphan","doi":"10.1177/2398212820939738","DOIUrl":"https://doi.org/10.1177/2398212820939738","url":null,"abstract":"<p><p>According to the standard theory of memory consolidation, recent memories are stored in the hippocampus before their transfer to cortical modules, a process called systemic consolidation. The ventral midline thalamus (reuniens and rhomboid nuclei, ReRh) takes part in this transfer as its lesion disrupts systemic consolidation of spatial and contextual fear memories. Here, we wondered whether ReRh lesions would also affect the systemic consolidation of another type of memory, namely an olfaction-based social memory. To address this question we focused on social transmission of food preference. Adult Long-Evans rats were subjected to N-methyl-d-aspartate-induced, fibre-sparing lesions of the ReRh nuclei or to a sham-operation, and subsequently trained in a social transmission of food preference paradigm. Retrieval was tested on the next day (recent memory, n_Sham = 10, n_ReRh = 12) or after a 25-day delay (remote memory, n_Sham = 10, n_ReRh = 10). All rats, whether sham-operated or subjected to ReRh lesions, learned and remembered the task normally, whatever the delay. Compared to our former results on spatial and contextual fear memories (Ali et al., 2017; Klein et al., 2019; Loureiro et al., 2012; Quet et al., 2020), the present findings indicate that the ReRh nuclei might not be part of a generic, systemic consolidation mechanism processing all kinds of memories in order to make them persistent. The difference between social transmission of food preference and spatial or contextual fear memories could be explained by the fact that social transmission of food preference is not hippocampus-dependent and that the persistence of social transmission of food preference memory relies on different circuits.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820939738"},"PeriodicalIF":0.0,"publicationDate":"2020-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820939738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403054","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":"The role of the locus coeruleus in the generation of pathological anxiety.","authors":"Laurel S Morris,&nbsp;Jordan G McCall,&nbsp;Dennis S Charney,&nbsp;James W Murrough","doi":"10.1177/2398212820930321","DOIUrl":"https://doi.org/10.1177/2398212820930321","url":null,"abstract":"<p><p>This review aims to synthesise a large pre-clinical and clinical literature related to a hypothesised role of the locus coeruleus norepinephrine system in responses to acute and chronic threat, as well as the emergence of pathological anxiety. The locus coeruleus has widespread norepinephrine projections throughout the central nervous system, which act to globally modulate arousal states and adaptive behavior, crucially positioned to play a significant role in modulating both ascending visceral and descending cortical neurocognitive information. In response to threat or a stressor, the locus coeruleus-norepinephrine system globally modulates arousal, alerting and orienting functions and can have a powerful effect on the regulation of multiple memory systems. Chronic stress leads to amplification of locus coeruleus reactivity to subsequent stressors, which is coupled with the emergence of pathological anxiety-like behaviors in rodents. While direct in vivo evidence for locus coeruleus dysfunction in humans with pathological anxiety remains limited, recent advances in high-resolution 7-T magnetic resonance imaging and computational modeling approaches are starting to provide new insights into locus coeruleus characteristics.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820930321"},"PeriodicalIF":0.0,"publicationDate":"2020-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820930321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403053","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":"Lateral entorhinal cortex lesions impair both egocentric and allocentric object-place associations.","authors":"Maneesh V Kuruvilla,&nbsp;David I G Wilson,&nbsp;James A Ainge","doi":"10.1177/2398212820939463","DOIUrl":"https://doi.org/10.1177/2398212820939463","url":null,"abstract":"<p><p>During navigation, landmark processing is critical either for generating an allocentric-based cognitive map or in facilitating egocentric-based strategies. Increasing evidence from manipulation and single-unit recording studies has highlighted the role of the entorhinal cortex in processing landmarks. In particular, the lateral (LEC) and medial (MEC) sub-regions of the entorhinal cortex have been shown to attend to proximal and distal landmarks, respectively. Recent studies have identified a further dissociation in cue processing between the LEC and MEC based on spatial frames of reference. Neurons in the LEC preferentially encode egocentric cues while those in the MEC encode allocentric cues. In this study, we assessed the impact of disrupting the LEC on landmark-based spatial memory in both egocentric and allocentric reference frames. Animals that received excitotoxic lesions of the LEC were significantly impaired, relative to controls, on both egocentric and allocentric versions of an object-place association task. Notably, LEC lesioned animals performed at chance on the egocentric version but above chance on the allocentric version. There was no significant difference in performance between the two groups on an object recognition and spatial T-maze task. Taken together, these results indicate that the LEC plays a role in feature integration more broadly and in specifically processing spatial information within an egocentric reference frame.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820939463"},"PeriodicalIF":0.0,"publicationDate":"2020-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820939463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403057","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":"Putting objects in context: A prefrontal-hippocampal-perirhinal cortex network.","authors":"G R I Barker,&nbsp;E C Warburton","doi":"10.1177/2398212820937621","DOIUrl":"https://doi.org/10.1177/2398212820937621","url":null,"abstract":"<p><p>When we encounter an object, we spontaneously form associations between the object and the environment in which it was encountered. These associations can take a number of different forms, which include location and context. A neural circuit between the hippocampus, medial prefrontal cortex and perirhinal cortex is critical for object-location and object-sequence associations; however, how this neural circuit contributes to the formation of object-context associations has not been established. Bilateral lesions were made in the hippocampus, medial prefrontal cortex or perirhinal cortex to examine each region contribution to object-context memory formation. Next, a disconnection lesion approach was used to examine the necessity of functional interactions between the hippocampus and medial prefrontal cortex or perirhinal cortex. Spontaneous tests of preferential exploration were used to assess memory for different types of object-context associations. Bilateral lesion in the hippocampus, medial prefrontal cortex or perirhinal cortex impaired performance in both an object-place-context and an object-context task. Disconnection of the hippocampus from either the medial prefrontal cortex or perirhinal cortex impaired performance in both the object-place-context and object-context task. Interestingly, when object recognition memory was tested with a context switch between encoding and test, performance in the hippocampal and medial prefrontal cortex lesion groups was disrupted and performance in each disconnection group (i.e. hippocampus + medial prefrontal cortex, hippocampus + perirhinal cortex) was significantly impaired. Overall, these experiments establish the importance of the hippocampal-medial prefrontal-perirhinal cortex circuit for the formation of object-context associations.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820937621"},"PeriodicalIF":0.0,"publicationDate":"2020-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820937621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403052","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":"Distributed interactive brain circuits for object-in-place memory: A place for time?","authors":"John P Aggleton,&nbsp;Andrew J D Nelson","doi":"10.1177/2398212820933471","DOIUrl":"https://doi.org/10.1177/2398212820933471","url":null,"abstract":"<p><p>Rodents will spontaneously learn the location of an individual object, an ability captured by the object-in-place test. This review considers the network of structures supporting this behavioural test, as well as some potential confounds that may affect interpretation. A hierarchical approach is adopted, as we first consider those brain regions necessary for two simpler, 'precursor' tests (object recognition and object location). It is evident that performing the object-in-place test requires an array of areas additional to those required for object recognition or object location. These additional areas include the rodent medial prefrontal cortex and two thalamic nuclei (nucleus reuniens and the medial dorsal nucleus), both densely interconnected with prefrontal areas. Consequently, despite the need for object and location information to be integrated for the object-in-place test, for example, via the hippocampus, other contributions are necessary. These contributions stem from how object-in-place is a test of associative recognition, as none of the individual elements in the test phase are novel. Parallels between the structures required for object-in-place and for recency discriminations, along with a re-examination of the demands of the object-in-place test, signal the integration of temporal information within what is usually regarded as a spatial-object test.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820933471"},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820933471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38403051","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":"Impairments in sensory-motor gating and information processing in a mouse model of <i>Ehmt1</i> haploinsufficiency.","authors":"Brittany A Davis, François David, Ciara O'Regan, Manal A Adam, Adrian J Harwood, Vincenzo Crunelli, Anthony R Isles","doi":"10.1177/2398212820928647","DOIUrl":"10.1177/2398212820928647","url":null,"abstract":"<p><p>Regulators of chromatin dynamics and transcription are increasingly implicated in the aetiology of neurodevelopmental disorders. Haploinsufficiency of <i>EHMT1</i>, encoding a histone methyltransferase, is associated with several neurodevelopmental disorders, including Kleefstra syndrome, developmental delay and autism spectrum disorder. Using a mouse model of <i>Ehmt1</i> haploinsufficiency (<i>Ehmt1</i> ^D6Cre/+), we examined a number of brain and behavioural endophenotypes of relevance to neurodevelopmental disorders. Specifically, we show that <i>Ehmt1</i> ^D6Cre/+ mice have deficits in information processing, evidenced by abnormal sensory-motor gating, a complete absence of object recognition memory, and a reduced magnitude of auditory evoked potentials in both paired-pulse inhibition and mismatch negativity. The electrophysiological experiments show that differences in magnitude response to auditory stimulus were associated with marked reductions in total and evoked beta- and gamma-band oscillatory activity, as well as significant reductions in phase synchronisation. The pattern of electrophysiological deficits in <i>Ehmt1</i> ^D6Cre/+ matches those seen in control mice following administration of the selective NMDA-R antagonist, ketamine. This, coupled with reduction of <i>Grin1</i> mRNA expression in <i>Ehmt1</i> ^D6Cre/+ hippocampus, suggests that <i>Ehmt1</i> haploinsufficiency may lead to disruption in NMDA-R. Taken together, these data indicate that reduced <i>Ehmt1</i> dosage during forebrain development leads to abnormal circuitry formation, which in turn results in profound information processing deficits. Such information processing deficits are likely paramount to our understanding of the cognitive and neurological dysfunctions shared across the neurodevelopmental disorders associated with <i>EHMT1</i> haploinsufficiency.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820928647"},"PeriodicalIF":0.0,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38500509","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":"Prefrontal-hippocampal interaction during the encoding of new memories.","authors":"Kaori Takehara-Nishiuchi","doi":"10.1177/2398212820925580","DOIUrl":"10.1177/2398212820925580","url":null,"abstract":"The hippocampus rapidly forms associations among ongoing events as they unfold and later instructs the gradual stabilisation of their memory traces in the neocortex. Although this two-stage model of memory consolidation has gained substantial empirical support, parallel evidence from rodent studies suggests that the neocortex, in particular the medial prefrontal cortex, might work in concert with the hippocampus during the encoding of new experiences. This opinion article first summarises findings from behavioural, electrophysiological, and molecular studies in rodents that uncovered immediate changes in synaptic connectivity and neural selectivity in the medial prefrontal cortex during and shortly after novel experiences. Based on these findings, I then propose a model positing that the medial prefrontal cortex and hippocampus might use different strategies to encode information during novel experiences, leading to the parallel formation of complementary memory traces in the two regions. The hippocampus captures moment-to-moment changes in incoming inputs with accurate spatial and temporal contexts, whereas the medial prefrontal cortex may sort the inputs based on their similarity and integrates them over time. These processes of pattern recognition and integration enable the medial prefrontal cortex to, in real time, capture the central content of novel experience and emit relevancy signal that helps to enhance the contrast between the relevant and incidental features of the experience. This hypothesis serves as a framework for future investigations on the potential top-down modulation that the medial prefrontal cortex may exert over the hippocampus to enable the selective, perhaps more intelligent encoding of new information.","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820925580"},"PeriodicalIF":0.0,"publicationDate":"2020-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212820925580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38500510","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":"Comparison of conventional and rapid-acting antidepressants in a rodent probabilistic reversal learning task.","authors":"Matthew P Wilkinson, John P Grogan, Jack R Mellor, Emma S J Robinson","doi":"10.1177/2398212820907177","DOIUrl":"10.1177/2398212820907177","url":null,"abstract":"<p><p>Deficits in reward processing are a central feature of major depressive disorder with patients exhibiting decreased reward learning and altered feedback sensitivity in probabilistic reversal learning tasks. Methods to quantify probabilistic learning in both rodents and humans have been developed, providing translational paradigms for depression research. We have utilised a probabilistic reversal learning task to investigate potential differences between conventional and rapid-acting antidepressants on reward learning and feedback sensitivity. We trained 12 rats in a touchscreen probabilistic reversal learning task before investigating the effect of acute administration of citalopram, venlafaxine, reboxetine, ketamine or scopolamine. Data were also analysed using a Q-learning reinforcement learning model to understand the effects of antidepressant treatment on underlying reward processing parameters. Citalopram administration decreased trials taken to learn the first rule and increased win-stay probability. Reboxetine decreased win-stay behaviour while also decreasing the number of rule changes animals performed in a session. Venlafaxine had no effect. Ketamine and scopolamine both decreased win-stay probability, number of rule changes performed and motivation in the task. Insights from the reinforcement learning model suggested that reboxetine led animals to choose a less optimal strategy, while ketamine decreased the model-free learning rate. These results suggest that reward learning and feedback sensitivity are not differentially modulated by conventional and rapid-acting antidepressant treatment in the probabilistic reversal learning task.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212820907177"},"PeriodicalIF":0.0,"publicationDate":"2020-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37777897","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":"The role of the immune system in driving neuroinflammation.","authors":"Caitlín Ní Chasaide,&nbsp;Marina A Lynch","doi":"10.1177/2398212819901082","DOIUrl":"https://doi.org/10.1177/2398212819901082","url":null,"abstract":"<p><p>Neuroinflammation is now recognised as an important contributory factor in the progression of Alzheimer's disease and probably also in the early stages of the disease. It is likely that this derives largely from aberrant activation of microglia, the resident mononuclear phagocytes of the brain. These cells are responsible for physiological immune surveillance and clearance of pathogens in the central nervous system, but evidence indicates that in Alzheimer's disease, microglial function is compromised, and this contributes to the pathology. It is unclear what factors cause the inappropriate activation of the microglia in Alzheimer's disease, but one contributor may be infiltrating peripheral immune cells and these include macrophages and T cells. It has been suggested that both cell types modulate the phenotype of microglia, highlighting the importance of crosstalk between the innate and adaptive immune system in Alzheimer's disease. This review outlines our current knowledge of how cells of the peripheral immune system, specifically macrophages and T cells, may modulate microglial phenotype in the context of Alzheimer's disease and considers the impact on their function, especially phagocytic capacity.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"4 ","pages":"2398212819901082"},"PeriodicalIF":0.0,"publicationDate":"2020-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212819901082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37777896","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}