해마 하위 영역 CA1과 CA3의 시각 자극 변화에 따른 장소 표상 패턴 연구

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2023. 2. 이인아.우리가 일상에서 경험하는 사건들은 하나의 스토리로 구성되어 일화 기억으로 형성된다. 해마는 과거에 경험한 일 들 뿐만 아니라 현재 경험하고 있는 사건들에 대한 일화 기억을 처리할 때 필수적인 뇌 영역이라고 알려져 있다. 설치류의 해마에서 관찰되는 장소 세포는 해마가 동물이 인지하고 있는 공간에 대한 지도를 형성하는 핵심적인 역할을 하는 것으로 알려져 있다. 특히 특정한 공간에서만 선별적으로 발화하는 장소 세포는 환경에 변화가 주어졌을 때 remapping이라는 현상으로 환경의 변화를 반영한다고 알려져 있다. 환경에 변화가 있을 때, 장소 세포가 동일한 위치에서 활동하며 발화 빈도를 조정하거나 전혀 다른 장소에서 활동하는 패턴으로 관찰된다. 이러한 장소 세포의 변화는 i) 기존의 기억을 조금 변형하거나, ii) 새로운 기억을 형성하는 일화 기억의 형태를 가지고 있다. 하지만 장소 세포가 불규칙적인 패턴으로 공간의 변화를 표상함에 따라 이들의 활동이 갖는 의미는 불분명하게 남아있다. 또한 장소 세포가 복합적인 감각 정보들을 반영한다는 특징은, 이들이 어떤 인지적 의미를 가지며 활동을 하는 것인지에 대한 난제를 남겼다. 본인은 해마의 장소 세포가 일화 기억에 어떤 기여를 할 것인지, 특히 변화된 환경에서 무엇을 새로 기억하고 기존에 알고 있는 정보는 어떻게 처리할 것인지 연산하는 과정을 해마의 하위 영역인 CA1과 CA3에서 각각 어떻게 표상하는지 알아보고자 하였다. 이에 대한 답을 찾기 위해 본인은 동물이 상호작용하며 경험할 수 있는 가상 현실 (VR) 시스템을 제작하여 가상 환경의 시각 자극을 정량적으로 조작하였다. 이 과정에서 본인은 동물이 경험하는 시각 자극의 변화와 (i.e., input) 해마 장소세포의 전기적 활동 (i.e., output) 간의 관계를 조사하였다. 첫 번째 질문으로는 본인이 구축한 가상 현실 시스템에서 장소 세포가 발현되는지를 확인하였다. 그 결과로 기존 문헌에서 보고되었던 결과와 비슷한 수준의 장소 세포들을 검증할 수 있었다. 본인이 구축한 가상 현실 시스템에서 장소 세포가 관찰된다는 것을 확인한 이후에는, 기존 환경에 정량적인 시각적 변화를 주어 장소 세포가 해당 변화를 어떻게 반영하는지 질문하였다. 그 결과로, 해마의 하위 영역 CA1에서 기존 환경에 대한 표상을 유지하는 집단과, 특정 환경에 변화가 가해진 사건에 의해 새로운 표상을 유지하는 집단이 동시다발적으로 나뉜다는 현상을 관찰하였다. 반면, 해마 하위 영역인 CA3에서는 환경에 변화가 이루어졌음에도 불구하고 대부분의 장소 세포들이 기존 환경에 대한 표상을 유지하였다. 이러한 결과를 토대로 해마 하위 영역인 CA3은 기존에 알고 있던 환경에 대한 기억을 안정적으로 유지하는 역할을 수행하는 반면, 해마 하위 영역인 CA1은 변화하는 환경 내에서도 이전의 기억과 새로운 기억을 독립적으로 구분하여 새로운 정보를 유연하게 학습하도록 하는 가능성을 제시하고자 한다.Any events or experiences in the given space and time are stitched together as an episode. The hippocampus has been widely acknowledged for its role in episodic memory for decades. At the same time, the rodent hippocampus exhibits the salient feature where its principal neurons are active in a spatially selective pattern (i.e., place cell). The place cells change their firing patterns as there are changes in the environments. Until now, we have been interpreting these firing changes, also known as "remapping," to have a functional significance in episodic memory by i) slightly modifying the old map to retrieve subtle changes from the previous memory or ii) forming the new map to reflect any major changes. In the real world, place cells receive complex sensory information from multiple sources, including multimodal sensory inputs and idiothetic information, making it even more challenging to interpret place cell activity from the intermingled sensory inputs fed into the hippocampal system. Taking advantage of the virtual reality (VR) system, I investigated how the hippocampal subregions CA1 and CA3 networks reflect environmental change. Thereby, I parametrically manipulated the environment by adding visual noise (i.e., virtual fog) in the VR environment and examined how hippocampal place cells in the CA1 and CA3 responded as visual noises were added to the environment in a quantified manner. Prior studies have suggested that CA3 forms a discrete map of the modified environments, presumably by performing either pattern separation or pattern completion. However, place cells in CA1 exhibit less coherent responses to environmental changes compared to CA3. This discrepancy between the CA1 and CA3 subregions is puzzling because CA3 output must pass through the CA1 area before reaching cortical areas. Furthermore, the functional roles of the CA1 in processing the environmental changes still need to be investigated due to the heterogeneous neural outputs with mixed yet conflicting findings. I first questioned whether our VR system reliably induced the place cells from both hippocampal subregions CA1 and CA3. As a result, I observed that the firing properties of hippocampal place cells are equivalent to that reported in the previous studies. Once I confirmed that visual environments in our VR system dominantly controlled the place cells, I examined how place cells in the CA1 and CA3 subregions responded to various levels of changes made to the visual environment. As visual noise was introduced to the familiar environment, I found that place cells in CA1 split simultaneously into two subpopulations: In one, place cells with old maps while changing their firing rate to reflect noise levels (i.e., rate remapping); in another, place cells with new maps to differentiate the dynamically changing environment from an old stable environment (i.e., global remapping). The place cells in CA3 mainly sustained the old map and reflected noise levels by rate remapping. Suppose one considers the rate remapping class of place cells as pattern-completing cells and the global remapping class as pattern-separating cells. In that case, the CA1 can manifest both pattern separation and pattern completion classes of neurons at the environmental change. My dissertation suggests that CA1 can simultaneously form an orthogonal map of the same environment to remember new episodes without interfering with the old memory.Background 1 Anatomical structures of the Hippocampal system and their proposed roles 2 The remapping properties of Hippocampal place cell 7 The usage of the virtual reality (VR) system for rodents in studying the hippocampus 16 Chapter 1. Visual scene stimulus exerts dominant control over the place fields 19 Introduction 20 Materials and methods 22 Results 37 Discussion 53 Chapter 2. The functional role of the CA1 and CA3 in processing the visually modified environment 56 Introduction 57 Materials and methods 59 Results 63 Discussion 94 General Discussion 98 Bibliography 111 국문초록 137박

The Construction of Semantic Memory: Grammar-Based Representations Learned from Relational Episodic Information

After acquisition, memories underlie a process of consolidation, making them more resistant to interference and brain injury. Memory consolidation involves systems-level interactions, most importantly between the hippocampus and associated structures, which takes part in the initial encoding of memory, and the neocortex, which supports long-term storage. This dichotomy parallels the contrast between episodic memory (tied to the hippocampal formation), collecting an autobiographical stream of experiences, and semantic memory, a repertoire of facts and statistical regularities about the world, involving the neocortex at large. Experimental evidence points to a gradual transformation of memories, following encoding, from an episodic to a semantic character. This may require an exchange of information between different memory modules during inactive periods. We propose a theory for such interactions and for the formation of semantic memory, in which episodic memory is encoded as relational data. Semantic memory is modeled as a modified stochastic grammar, which learns to parse episodic configurations expressed as an association matrix. The grammar produces tree-like representations of episodes, describing the relationships between its main constituents at multiple levels of categorization, based on its current knowledge of world regularities. These regularities are learned by the grammar from episodic memory information, through an expectation-maximization procedure, analogous to the inside–outside algorithm for stochastic context-free grammars. We propose that a Monte-Carlo sampling version of this algorithm can be mapped on the dynamics of “sleep replay” of previously acquired information in the hippocampus and neocortex. We propose that the model can reproduce several properties of semantic memory such as decontextualization, top-down processing, and creation of schemata

Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies

SummaryBoth episodic memory and spatial navigation require temporal encoding of the relationships between events or locations. In a linear maze, ordered spatial distances between sequential locations were represented by the temporal relations of hippocampal place cell pairs within cycles of theta oscillation in a compressed manner. Such correlations could arise due to spike “phase precession” of independent neurons driven by common theta pacemaker or as a result of temporal coordination among specific hippocampal cell assemblies. We found that temporal correlation between place cell pairs was stronger than predicted by a pacemaker drive of independent neurons, indicating a critical role for synaptic interactions and precise timing within and across cell assemblies in place sequence representation. CA1 and CA3 ensembles, identifying spatial locations, were active preferentially on opposite phases of theta cycles. These observations suggest that interleaving CA3 neuronal sequences bind CA1 assemblies representing overlapping past, present, and future locations into single episodes

치상회 손상에 따른 CA3 장소세포의 장면의존적 발화율 변조의 저하

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 뇌인지과학과, 2020. 8. 이인아.The ability to differentiate similar experiences into discrete events in memory is a fundamental component of the episodic memory. Computational models and experimental evidence have suggested that projections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this thesis, the simultaneous application of lesion and in-vivo electrophysiology were used to examine the role of the DG inputs to the CA3 as the animal processes scene memory. Selective lesions in the DG were made using colchicine in male Long-Evans rats, and CA3 single units were recorded as the rats performed visual scene memory tasks. The original scenes used in training were modified during testing by blurring to varying degrees, by using visual masks, or by overlaying competing scenes to examine how changes in scenes differentially recruit the DG-CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. The firing-rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when blurred scenes were presented, largely because DG-deprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.특정 환경에 적합한 행동을 하기 위해 우리는 과거에 그 환경에서 어떠한 경험을 하였는지 반추한다. 해마는 이와 같이 과거에 경험한 사건 등에 대한 일화 기억을 처리할 때 중요한 뇌 영역이라고 알려져 있다. 항상 변화하는 환경 속에서 매번 과거와 동일한 자극을 경험하긴 어렵다. 따라서, 일화 기억의 처리에는 서로 유사하지만 다른 상황을 구분하는 과정이 필요하다. 해마의 하위 영역인 치상회는 서로 유사한 자극을 분리하여 저장하기 위해 필요하다고 알려져 있으나, 단위신경세포 수준의 정보처리 기전은 아직 알려진 바 없다. 이 논문에서는 최근 일화 기억의 저장과 인출 과정이 시각적으로 들어오는 장면에 대한 처리와 밀접한 연관을 가지고 있다는 주장에 기반하여, 유사한 장면 자극들이 해마에서 처리되는 기전에 대한 연구를 진행하였다. 이 연구에서는 콜치신을 사용한 쥐의 치상회의 손상이 시각 장면 기억 과제의 수행을 저해하는지 그 행동적 영향을 검증하였다. 또한, 치상회로부터 정보를 받는 CA3영역의 단위신경세포의 활동 전위가 어떠한 방식으로 장면 자극을 표상하고, 기존에 학습했던 장면 자극이 변형되었을 때는 어떻게 표상하는지, 그리고 그 표상 방식들이 치상회의 손상 여부에 따라 어떻게 영향을 받는지 전기생리학적 검증을 시도하였다. 통제 집단에 비해 치상회 손상 집단은 기존에 학습하였던 장면 자극이 흐릿하게 제시될 때에만 낮은 과제 수행률을 보였다. 동시에 치상회가 손상된 쥐들의 CA3 단위신경세포의 시각 장면 관련 발화율 변조가 흐릿한 장면 자극이 제시되었을 때 현저하게 감소하였다. 이는 치상회가 손상된 쥐의 CA3 단위신경세포가 통제 집단에 비해 흐릿한 장면 자극의 모호성의 정도에 따른 범주적 변화를 보여주지 않았기 때문이다. 본 연구는 치상회가 CA3 영역이 애매한 장면에 직교적으로 반응하게 함으로써 장면 기억을 저장하는 과정뿐만 아니라, CA3와 함께 수정된 시각 장면이 처리될 때에도 핵심적인 역할을 한다는 것을 규명하였다.Chapter 1. Recognition of ambiguous visual scenes following the lesion of the dentate gyrus 12 Introduction 13 Materials and methods 14 Results 26 Discussion 33 Chapter 2. Impaired pattern separation in scene-dependent rate modulation in CA3 single units following the lesion of the dentate gyrus 36 Introduction 37 Materials and methods 38 Results 49 Discussion 75 General Discussion 77 Bibliography 85 Acknowledgement (감사의 말) 97 국문초록 98Docto

Mechanisms of memory consolidation : Analyzing the coordinated activity of concept neurons in the human medial temporal lobe during waking and sleep

The aim of this thesis is to investigate the role of human concept neurons in memory consolidation during sleep. Memory consolidation is a process by which memories initially dependent on the hippocampus are transferred to cortical areas, thereby gradually becoming independent of the hippocampus. Theories of memory consolidation posit that memory traces encoding autobiographic episodes are rapidly formed in the hippocampus during waking, and reactivated during subsequent slow-wave sleep to be transformed into a long-lasting form. Concept neurons in the human medial temporal lobe are neurons tuned to semantic concepts in a selective, sparse, and invariant manner. These neurons respond to pictures or written and spoken words representing their preferred concept (for example, a person, an animal, an object), regardless of physical stimulus properties. Concept neurons have been speculated to be building blocks for episodic memory. We used whole-night recordings from concept neurons in the medial temporal lobe of epilepsy patients implanted with depth electrodes for presurgical monitoring to test the hypothesis that the coordinated activity of concept neurons during sleep is a neurophysiological correlate of memory consolidation in humans. To conduct this study, we developed software methods for artifact removal and spike sorting of long-term recordings from single neurons. In an evaluation on both simulated model data and visual stimulus presentation experiments, our software outperformed previous methods. Starting from the conceptual analogy between rodent place cells and human concept neurons, we developed an episodic memory task in which participants learned a story eliciting sequential activity in concept neurons. We found that concept neurons preserved their semantic tuning across whole-night recordings. Hippocampal concept neurons had, on average, lower firing rates during rapid-eye-movement (REM) sleep than during waking. During slow-wave sleep, firing rates did not significantly differ from waking. The activity of concept neurons increased during ripples in the local field potential. Furthermore, concept neurons whose preferred stimuli participated in the memorized story were conjointly reactivated after learning, most pronouncedly during slow-wave sleep. Cross-correlations of concept neurons were most asymmetric during slow-wave sleep. Cross-correlation peak times were often in the range believed to be relevant for spike-timing-dependent plasticity. However, time lags of peak cross-correlations did not correlate with the positional order of stimuli in the memorized story. Our findings support the hypothesis that concept neurons rapidly encode a memory trace during learning, and that the reactivation of the same neurons during subsequent slow-wave sleep and ripples contributes to the consolidation of the memory episode. However, the consolidation of the temporal order of events in humans appears to differ from what rodent research suggests.Mechanismen der Gedächtniskonsolidierung : Analyse der Aktivität von Konzeptzellen im menschlichen Schläfenlappen während Wachheit und Schlaf In dieser Arbeit wird die Rolle von Konzeptzellen ("concept neurons") im Gehirn des Menschen bei der Gedächtniskonsolidierung im Schlaf untersucht. Gedächtniskonsolidierung ist ein Prozess, durch den Gedächtnisinhalte, die zunächst vom Hippokampus abhängen, in die Großhirnrinde übertragen werden. Dadurch reduziert sich im Laufe der Zeit die Abhängigkeit der Gedächtnisinhalte vom Hippokampus. In der Theorie der Gedächtniskonsolidierung wird angenommen, dass während wachem Erleben sehr schnell Gedächtnisspuren im Hippokampus entstehen, welche im darauffolgenden Tiefschlaf reaktiviert werden, um so eine langfristig stabile Gedächtnisspur zu erzeugen. Konzeptzellen im Schläfenlappen des Menschen sind Nervenzellen, die auf den semantischen Inhalt eines Stimulus selektiv und semantisch invariant reagieren. Konzeptzellen antworten auf Abbildungen ihres präferierten Konzepts (zum Beispiel einer Person, eines Tieres oder eines Objekts) oder auf geschriebene und gesprochene Wörter, die das gleiche Konzept darstellen, unabhängig von den speziellen Eigenschaften des Stimulus, wie zum Beispiel Bildgröße oder -farbe. Auf jedes Konzept reagiert dabei nur ein sehr kleiner Teil dieser Zellen. Man vermutet, dass Konzeptzellen Bausteine des episodischen Gedächtnisses sind. Die vorliegende Studie nutzt Aufzeichnungen der Aktivität einzelner Konzeptzellen während ganzer Nächte, um zu untersuchen, inwiefern die koordinierte Aktivität von Konzeptzellen im Schlaf ein neurophysiologisches Korrelat der Gedächtniskonsolidierung darstellt. Die Teilnehmer der Studie waren Epilepsiepatienten, in deren mediale Schläfenlappen aus klinischen Gründen Tiefenelektroden zur Anfallsaufzeichnung implantiert worden waren. Zur Analyse der Daten wurde zunächst eine Software entwickelt, die eine Artefaktbereinigung und das Spike-Sorting von neuronalen Langzeitaufzeichnungen leistet. Diese Software zeigte deutliche Vorteile gegenüber vorhandenen Methoden, und zwar sowohl in Tests mit simulierten Modelldatensätzen als auch im Falle tatsächlicher Aufzeichnungen (hier Experimente, in denen visuelle Stimuli auf einem Laptop dargestellt wurden). Ausgehend von einer Analogie zwischen Ortszellen ("place cells") bei Nagetieren und Konzeptzellen bei Menschen wurde ein Experiment entwickelt, das episodisches Gedächtnis operationalisierte. Darin lernten die Teilnehmer eine kurze Geschichte auswendig, was sequentielle Aktivität von Konzeptzellen auslöste. Konzeptzellen zeigten ein stabiles Antwortverhalten: am Abend und nächsten Morgen antworteten sie auf die gleichen Stimuli. Konzeptzellen im Hippokampus hatten im Mittel im Rapid-Eye-Movement-Schlaf (REM-Schlaf) niedrigere Feuerraten als während Wachheit. Im Tiefschlaf unterschieden sich die Feuerraten nicht signifikant von Wachheit. Die Aktivität der Konzeptzellen war während "ripples" im lokalen Feldpotential erhöht, und Konzeptzellen, deren präferierte Stimuli in der erinnerten Geschichte auftauchten, feuerten im darauffolgenden Schlaf gemeinsam, ein Effekt, der im Tiefschlaf besonders ausgeprägt war. Die Kreuzkorrelationen von Konzeptzellen waren im Tiefschlaf asymmetrischer als während Wachheit und REM-Schlaf, und die typischen Zeitabstände des Feuerns von Konzeptzellen lagen in einem Bereich, der als relevant für "spike-timing-dependent plasticity" gilt. Die Zeitabstände waren jedoch nicht mit dem Abstand der präferierten Stimuli in der erinnerten Geschichte korreliert. Diese Befunde stützen die Theorie, dass die Aktivität von Konzeptzellen während des Lernens instantan eine Gedächtnisspur erzeugt, und dass die Reaktivierung der gleichen Nervenzellen im Tiefschlaf nach dem Lernen zur Konsolidierung der Gedächtnisinhalte beiträgt. Die zeitliche Reihenfolge von Ereignissen wird offenbar im menschlichen Gehirn nicht auf die Weise konsolidiert, die sich aus der Forschung an Nagetieren nahelegte

Hippocampal Replay of Extended Experience

During pauses in exploration, ensembles of place cells in the rat hippocampus re-express firing sequences corresponding to recent spatial experience. Such “replay” co-occurs with ripple events: short-lasting (∼50–120 ms), high-frequency (∼200 Hz) oscillations that are associated with increased hippocampal-cortical communication. In previous studies, rats exploring small environments showed replay anchored to the rat's current location and compressed in time into a single ripple event. Here, we show, using a neural decoding approach, that firing sequences corresponding to long runs through a large environment are replayed with high fidelity and that such replay can begin at remote locations on the track. Extended replay proceeds at a characteristic virtual speed of ∼8 m/s and remains coherent across trains of ripple events. These results suggest that extended replay is composed of chains of shorter subsequences, which may reflect a strategy for the storage and flexible expression of memories of prolonged experience.Massachusetts Institute of Technology. Department of Brain and Cognitive Science (Singleton Fellowship)National Institutes of Health (U.S.) (grant MH061976

Replay of memories of extended behavior in the rat hippocampus

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009.Cataloged from PDF version of thesis.Includes bibliographical references.The hippocampus is a highly conserved structure in the medial temporal lobe of the brain that is known to be critical for spatial learning in rodents, and spatial and episodic memory in humans. During pauses in exploration, ensembles of place cells in the rat hippocampus re-express firing sequences corresponding to recent spatial experience. Such 'replay' co-occurs with ripple events: short-lasting (~50-120 ms), high frequency (-200 Hz) oscillations that are associated with increased hippocampal-cortical communication. In previous studies, rats explored small environments, and replay was found to be anchored to the rat's current location, and compressed in time such that replay of the complete environment occurred during a single ripple event. In this thesis, we develop a probabilistic neural decoding approach that allows us to show that firing sequences corresponding to long runs through a large environment are replayed with high fidelity (in both forward and reverse order). We show that such replay can begin at remote locations on the track, and proceeds at a characteristic virtual speed of -8 m/s. Replay remains coherent across trains of sharp wave-ripple events. These results suggest that extended replay is composed of chains of shorter subsequences, which may reflect a strategy for the storage and flexible expression of memories of prolonged experience. We discuss the evidence for the operation of similar mechanisms in humans.by Thomas James Davidson.Ph.D

IST Austria Thesis

The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision

Execution of new trajectories towards a stable goal without a functional hippocampus

The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a “replay” of an animal's past trajectories. A novel spatial navigation task recently revealed that such “replay” sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such “prospective replay” sequences may play a causal role in goal-directed navigation. In the present study, we query this putative causal role in finding only minimal effects of muscimol-induced inactivation of the dorsal and intermediate hippocampus on the same spatial navigation task. The concentration of muscimol used demonstrably inhibited hippocampal cell firing in vivo and caused a severe deficit in a hippocampal-dependent “episodic-like” spatial memory task in a watermaze. These findings call into question whether “prospective replay” of an imminent and direct path is actually necessary for its execution in certain navigational tasks.Aarhus Institute of Advanced Studies, AarhusUniversitet, Grant/Award Number: 754513;ICT-FET (European Commission), Grant/AwardNumber: 600725; Lundbeckfonden,Grant/Award Number: DANDRITE-R248-2016-2518; Novo Nordisk Fonden,Grant/Award Number: NNF17OC0026774;Wellcome Trust, Grant/Award Numbers:206491, 207481/Z/17/Z; European Molecular Biology Organization, Grant/Award Number:EMBOALTF382-2017Peer reviewe

A Review of Findings from Neuroscience and Cognitive Psychology as Possible Inspiration for the Path to Artificial General Intelligence

This review aims to contribute to the quest for artificial general intelligence by examining neuroscience and cognitive psychology methods for potential inspiration. Despite the impressive advancements achieved by deep learning models in various domains, they still have shortcomings in abstract reasoning and causal understanding. Such capabilities should be ultimately integrated into artificial intelligence systems in order to surpass data-driven limitations and support decision making in a way more similar to human intelligence. This work is a vertical review that attempts a wide-ranging exploration of brain function, spanning from lower-level biological neurons, spiking neural networks, and neuronal ensembles to higher-level concepts such as brain anatomy, vector symbolic architectures, cognitive and categorization models, and cognitive architectures. The hope is that these concepts may offer insights for solutions in artificial general intelligence.Comment: 143 pages, 49 figures, 244 reference