Associative Memory Storage and Retrieval: Involvement of Theta Oscillations in Hippocampal Information Processing

Theta oscillations are thought to play a critical role in neuronal information processing, especially in the hippocampal region, where their presence is particularly salient. A detailed description of theta dynamics in this region has revealed not only a consortium of layer-specific theta dipoles, but also within-layer differences in the expression of theta. This complex and articulated arrangement of current flows is reflected in the way neuronal firing is modulated in time. Several models have proposed that these different theta modulators flexibly coordinate hippocampal regions, to support associative memory formation and retrieval. Here, we summarily review different approaches related to this issue and we describe a mechanism, based on experimental and simulation results, for memory retrieval in CA3 involving theta modulation

A scientific theory of ars memoriae : spatial view cells in a continuous attractor network with linked items

The art of memory (ars memoriae) used since classical times includes using a well-known scene to associate each view or part of the scene with a different item in a speech. This memory technique is also known as the “method of loci.” The new theory is proposed that this type of memory is implemented in the CA3 region of the hippocampus where there are spatial view cells in primates that allow a particular view to be associated with a particular object in an event or episodic memory. Given that the CA3 cells with their extensive recurrent collateral system connecting different CA3 cells, and associative synaptic modifiability, form an autoassociation or attractor network, the spatial view cells with their approximately Gaussian view fields become linked in a continuous attractor network. As the view space is traversed continuously (e.g., by self-motion or imagined self-motion across the scene), the views are therefore successively recalled in the correct order, with no view missing, and with low interference between the items to be recalled. Given that each spatial view has been associated with a different discrete item, the items are recalled in the correct order, with none missing. This is the first neuroscience theory of ars memoriae. The theory provides a foundation for understanding how a key feature of ars memoriae, the ability to use a spatial scene to encode a sequence of items to be remembered, is implemented

The mechanisms for pattern completion and pattern separation in the hippocampus

The mechanisms for pattern completion and pattern separation are described in the context of a theory of hippocampal function in which the hippocampal CA3 system operates as a single attractor or autoassociation network to enable rapid, one-trial, associations between any spatial location (place in rodents, or spatial view in primates) and an object or reward, and to provide for completion of the whole memory during recall from any part. The factors important in the pattern completion in CA3 together with a large number of independent memories stored in CA3 include a sparse distributed representation which is enhanced by the graded firing rates of CA3 neurons, representations that are independent due to the randomizing effect of the mossy fibers, heterosynaptic long-term depression as well as long-term potentiation in the recurrent collateral synapses, and diluted connectivity to minimize the number of multiple synapses between any pair of CA3 neurons which otherwise distort the basins of attraction. Recall of information from CA3 is implemented by the entorhinal cortex perforant path synapses to CA3 cells, which in acting as a pattern associator allow some pattern generalization. Pattern separation is performed in the dentate granule cells using competitive learning to convert grid-like entorhinal cortex firing to place-like fields. Pattern separation in CA3, which is important for completion of any one of the stored patterns from a fragment, is provided for by the randomizing effect of the mossy fiber synapses to which neurogenesis may contribute, by the large number of dentate granule cells each with a sparse representation, and by the sparse independent representations in CA3. Recall to the neocortex is achieved by a reverse hierarchical series of pattern association networks implemented by the hippocampo-cortical backprojections, each one of which performs some pattern generalization, to retrieve a complete pattern of cortical firing in higher-order cortical areas

Modeling hippocampal theta-coupled gamma oscillations in learning and memory

Two of the most researched domains in the hippocampus are the oscillatory activity and encoding and retrieval of patterns in the hippocampal CA1 and CA3 regions. They are, how- ever, not studied together; and hence, the objective of our work is to study the cross-frequency coupling of theta-coupled gamma oscillations in CA1 and CA3 regions of the hippocampus while encoding and retrieving information. We have studied the cross-frequency coupling of theta-coupled gamma oscillations both individually and in our newly-proposed integrated model of CA1-CA3 to analyze the effects of Schaffer collaterals and CA1 back-projection cells on CA1 and CA3 regions of the hippocampus. Due to lack of literary evidence, we have also contributed our hypotheses about the effects of CA1 back-projection cells on CA1 and CA3 cell-types. Moreover, we have developed a deterministic rule-based cellular automata library to study cross-frequency coupling in single-neuron level and population neuronal net- works at the same time. The discrete model is theta-oscillations-aware and hence encoding and retrieving of patterns takes place during the half-cycles of theta oscillations. We have extended the septo-hippocampal population firing rate model proposed by Den- ham and Borisyuk (2000) to study (i) the influence of inhibitory interneurons, specifically PV-containing basket cells (BCs) and bistratified cells (BSCs) on theta and theta-coupled gamma oscillations in both CA1 and CA3 hippocampal networks; (ii) to study Schaffer col- laterals from CA3 to CA1 and the influence of back-projection cells in CA1 on CA3; (iii) to analyze and compare the phases of cross-frequency coupling of theta-coupled gamma oscil- lations among the different cell types in CA1 and CA3 regions; (iv) to study the influence of external inputs on CA1 and CA3. In our simulations, with constant external inputs, we identify the parameter regions that generate theta oscillations and that BCs and BSCs in CA1 are in anti-phase, as seen experi- mentally by Klausberger et. al (2008). Slow-gamma oscillations are generated due to the ac- tivity of BSCs and BCs in CA1 and CA3, and they are propagated from CA3 to CA1 through the Schaffer collaterals, as seen in Klausberger et. al (2008) where BSCs were observed to synchronize PC activity during theta-coupled gamma oscillations in CA1. In CA3, increas- ing excitation of CA3 pyramidal cells results in theta oscillations without the slow-gamma coupling. Increasing excitatory input to CA1 pyramidal cells results in steady state and de- creasing the excitatory input, results in reduced oscillatory activity in both CA1 and CA3 due to Schaffer collaterals and the feedback projections from CA1 to CA3. This demonstrates that changes in input excitation can move the networks from oscillatory to non-oscillatory states, comparable to the differences seen in animals between exploratory and resting state. Further, Mizuseki et. al (2009) observed experimentally that CA1, CA3 and EC are out- of-theta-phase with each other and that the phase observed in CA1 pyramidal cells are not a result of a simple integration of phases from CA3, EC or the medial septum. We have thus, simulated theta-frequency sine-wave inputs from CA3 and EC of relative phases in the model and observed the same results in our CA1 individual and CA1-CA3 integrated model. To study encoding and retrieval of patterns in an oscillating model, we took an engineer- ing approach by developing a discrete modeling system using cellular automata (CA) derived from the models of Pytte et. al (1991) and Claverol et. al (2002). The aim of this model is to (i) replicate the oscillatory and phasic results obtained using the continuous modeling ap- proach and (ii) extend the same model to study storage and recall of patterns in CA1 taking a theta-oscillations-aware approach. Encoding and retrieval happen at different half-cycles of theta where information pro- cessing takes places in the sub-cycles of the slow-gamma oscillations in each half-cycle of theta oscillation (Cutsuridis et. al, 2010, Hasselmo et. al, 1996). A set of rules is developed to replicate this for the CA model of CA1. The encoding and retrieval half-cycles are identi- fied using the basket cell activity, and hence synaptic learning is enabled during the encoding half-cycle of theta, and is disabled during the recall half-cycle of theta oscillations. This is also a biologically realistic enhancement for studying learning and recall in theta-coupled gamma oscillations using a discrete cellular automata approach

Spatial Representations in the Entorhino-Hippocampal Circuit

After a general introduction and a brief review of the available experimental data on spatial representations (chapter 2), this thesis is divided into two main parts. The first part, comprising the chapters from 3 to 6, is dedicated to grid cells. In chapter 3 we present and discuss the various models proposed for explaining grid cells formation. In chapter 4 and 5 we study our model of grid cells generation based on adaptation in the case of non-planar environments, namely in the case of a spherical environment and of three-dimensional space. In chapter 6 we propose a variant of the model where the alignment of the grid axes is induced through reciprocal inhibition, and we suggest that that the inhibitory connections obtained during this learning process can be used to implement a continuous attractor in mEC. The second part, comprising chapters from 7 to 10 is instead focused on place cell representations. In chapter 7 we analyze the differences between place cells and grid cells in terms on information content, in chapter 8 we describe the properties of attractor dynamics in our model of the Ca3 net- work, and in the following chapter we study the effects of theta oscillations on network dynamics. Finally, in Chapter 10 we analyze to what extent the learning of a new representation, can preserve the topology and the exact metric of physical space

해마 하위 영역 CA1과 CA3의 장면 자극에 기반한 장소 표상 형성 연구

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 뇌인지과학과, 2021. 2. 이인아.When we recall the past experiences, we usually think of a scene which is a combination of what we saw, the sounds we hear, and the feeling we felt at that moment. Since the scene is an essential component of episodic memory, studying how scene stimuli are represented and stored in the brain is important in understanding the processes of formation, storage, and retrieval of our memories. One of the brain regions important for episodic memory is the hippocampus. It has been reported that patients or animals with damage to the hippocampus have trouble with retrieving past experiences or forming new memories. The hippocampus is involved not only in episodic memory but also in the formation of a cognitive map. In particular, the place cells observed in the rodent hippocampus play a key role in these functions. However, research on place cells has mainly focused on the firing patterns of cells during foraging in a space, and it has not been clear how hippocampal cells represent and make use of visual scenes for behavior. To find how scene stimuli are represented in place cells, I measured spiking activities of single neurons in the CA1, one of the subregions of hippocampus, and the subiculum, a major output of the hippocampus. Neuronal spiking activity was monitored when the rat performed a task of selecting right or left associated to the scene stimulus presented on monitors. As a result, I found that the place cells in the CA1 and subiculum showed rate modulation according to the scene stimulus. In addition, I also conducted an experiment using a virtual reality system to investigate the neural mechanisms of the formation of a place field based on visual scenes. In this experiment, the rat ran on a virtual linear track as visual cues were added one by one to make a scene-like environment. Neuronal activities of place cells were recorded in the CA1 and CA3 simultaneously to study the neural mechanisms of the development of a place field on the basis of external visual stimuli. Place fields appeared in the CA1 even with a single visual cue, whereas in the CA3, place fields only emerged when a sufficient number of visual cues were collectively arranged in a scene-like fashion. The results suggest that that scene is one of the key stimulus that effectively recruits the hippocampus.우리는 과거의 경험을 떠올릴 때 그 때를 묘사하는 문장을 떠올리는 것이 아니라 경험 한 순간에 보았던 것, 들렸던 소리, 느꼈던 감정 등이 복합적으로 어우러진 장면을 떠올리게 된다. 이렇게 장면은 일화 기억을 구성하는 중요한 요소라 할 수 있기에 장면 자극이 뇌에서 어떻게 표상되며 저장되는지를 연구하는 것은 우리 기억의 형성과 저장, 재인 과정을 이해하는데 있어 매우 중요하다고 볼 수 있다. 뇌에서 일화 기억을 담당한다고 알려진 영역은 해마로써, 해마에 손상을 입은 환자들 또는 동물들이 과거의 기억을 인출하거나 새로운 기억을 형성하는데 있어 어려움을 겪는다는 것이 여러 실험을 통해 보고 된 바 있다. 해마는 일화 기억뿐만 아니라 공간에 대한 지도를 형성하는 데에도 관여하는데, 특히, 설치류 해마에서 관찰 되는 장소 세포가 이러한 해마의 기능들을 수행하는데 핵심적인 역할을 하는 것으로 알려져 있다. 하지만 장소 세포는 주로 쥐가 공간을 탐색하는 과정에서의 발화 패턴을 관측한 연구가 주를 이루었으며 장면 자극이 개별 장소 세포의 발화 패턴을 통해 어떻게 표상이 되는지에 대한 연구는 미미한 수준이다. 이 논문에서 나는 장면 자극이 해마의 장소 세포에서 어떻게 표상되는지를 알아보고자 쥐가 모니터에 제시 된 장면 자극을 보고 오른쪽이나 왼쪽을 선택해야 하는 과제를 수행 할 때 해마의 하위 영역인 CA1과 해마의 정보를 전달 받아 뇌의 다른 영역으로 정보를 전달하는 해마이행부의 단일 세포 활동을 측정하였다. 그 결과 CA1과 해마이행부에서 관찰 된 장소 세포들이 장면 자극에 따른 발화율 변화를 보인다는 것을 확인 할 수 있었다. 이에 더하여 나는 해마의 장소 세포들이 장소장을 형성하기 위해서 필요한 시각 자극이 무엇이며, 이에 장면 자극이 어떤 역할을 하는지 확인하기 위해 가상 환경을 이용한 실험을 수행하였다. 이 실험에서는 쥐가 선형 트랙을 달릴 때, 빈 공간에서 시작하여 장면 자극을 형성 할 때까지 시각 자극을 하나씩 추가하면서 해마의 하위 영역인 CA1과 CA3의 장소 세포 활동을 측정 하는 과정을 통해 어떤 시각 자극이 장소 세포의 장소장 형성에 가장 큰 영향을 미치는 것인지 알아보았다. 그 결과 CA1의 장소 세포는 간단한 시각 자극의 추가에도 장소장을 잘 형성하는 모습을 보인 반면 CA3의 장소 세포들은 충분한 시각 자극이 모여서 장면 자극을 형성 한 경우에 장소장을 형성하는 것이 관찰되었다. 이러한 일련의 실험을 통하여 나는 장면 자극이 해마의 장소 세포 발화를 통해 표상되며, 해마의 하위 영역이 모두 장면 자극 처리에 관여하지만 그 중에서도 특히 CA3가 장면 자극을 처리 할 때에 한하여 큰 활성을 보인다는 것을 밝혔다.Abstract i Table of Contents iii List of Figures iv Background 1 Scene processing in the hippocampus 2 Anatomical connections of CA1 and CA3 4 Properties of place cell activity 7 Chapter 1. Visual scene representation of CA1 and subiculum in the visual scene memory task 10 Introduction 11 Materials and methods 14 Results 31 Discussion 60 Chapter 2. Role of the visual scene stimulus for place field formation in CA1 and CA3 65 Introduction 66 Materials and methods 68 Results 80 Discussion 107 General Discussion 118 Bibliography 124 국문초록 140Docto

Storage, recall, and novelty detection of sequences by the hippocampus: Elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine

ABSTRACT: In order to understand how the molecular or cellular defects that underlie a disease of the nervous system lead to the observ-able symptoms, it is necessary to develop a large-scale neural model. Such a model must specify how specific molecular processes contribute to neuronal function, how neurons contribute to network function, and how networks interact to produce behavior. This is a challenging undertaking, but some limited progress has been made in understanding the memory functions of the hippocampus with this degree of detail. There is increas-ing evidence that the hippocampus has a special role in the learning of sequences and the linkage of specific memories to context. In the first part of this paper, we review a model (the SOCRATIC model) that describes how the dentate and CA3 hippocampal regions could store and recall memory sequences in context. A major line of evidence for sequence recall is the “phase precession ” of hippocampal place cells. In the second part of the paper, we review the evidence for theta-gamma phase coding