抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.

/pdf/microstructure-of-a-spatial-map-in-the-entorhinal-cortex-511e186u79.pdf

Microstructure of a spatial map in the entorhinal cortex

Mechanisms and functional implications of adult neurogenesis.

The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there is considerable debate about how these kinds of memory are supported by regions in the medial temporal lobes (MTL). Here, we review evidence for the distinction between recollection and familiarity and then consider the evidence regarding the neural mechanisms of these processes. Evidence from neuropsychological, neuroimaging, and neurophysiological studies of humans, monkeys, and rats indicates that different subregions of the MTL make distinct contributions to recollection and familiarity. The data suggest that the hippocampus is critical for recollection but not familiarity. The parahippocampal cortex also contributes to recollection, possibly via the representation and retrieval of contextual (especially spatial) information, whereas perirhinal cortex contributes to and is necessary for familiarity-based recognition. The findings are consistent with an anatomically guided hypothesis about the functional organization of the MTL and suggest mechanisms by which the anatomical components of the MTL interact to support the phenomenology of recollection and familiarity.

The Medial Temporal Lobe and Recognition Memory

The integration of adult-born neurons into the circuitry of the adult hippocampus suggests an important role for adult hippocampal neurogenesis in learning and memory, but its specific function in these processes has remained elusive. In this article, we summarize recent progress in this area, including advances based on behavioural studies and insights provided by computational modelling. Increasingly, evidence suggests that newborn neurons might be involved in hippocampal functions that are particularly dependent on the dentate gyrus, such as pattern separation. Furthermore, newborn neurons at different maturation stages may make distinct contributions to learning and memory. In particular, computational studies suggest that, before newborn neurons are fully mature, they might function as a pattern integrator by introducing a degree of similarity to the encoding of events that occur closely in time.

/pdf/new-neurons-and-new-memories-how-does-adult-hippocampal-1cksch4hdk.pdf

New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?

Hippocampal place cells are a model system of how the brain constructs cognitive representations and of how these representations support complex behavior, learning, and memory There is, however, a lack of detailed knowledge about the properties of hippocampal afferents We recorded multiple single units from the hippocampus and the medial and lateral entorhinal areas of behaving rats Although many medial entorhinal neurons had highly specific place fields, lateral entorhinal neurons displayed weak spatial specificity This finding demonstrates a fundamental dissociation between the information conveyed to the hippocampus by its major input streams, with spatial information represented by the medial and nonspatial information represented by the lateral entorhinal cortex

https://science.sciencemag.org/content/sci/308/5729/1792.full.pdf

Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus

This study presents a double dissociation between the dentate gyrus (DG) and CA1. Rats with either DG or CA1 lesions were tested on tasks requiring either spatial or spatial temporal order pattern separation. To assess spatial pattern separation, rats were trained to displace an object which covered a baited food-well. The rats were then allowed to choose between two identical objects: one covered the same well as the sample phase object (correct choice), and a second object covered a different unbaited well (incorrect choice). Spatial separations of 15-105 cm were used to separate the correct object from the incorrect object. To assess spatial temporal order pattern separation, rats were allowed to visit each arm of a radial eight-arm maze once in a randomly determined sequence. The rats were then presented with two arms and were required to choose the arm which occurred earliest in the sequence. The choice arms varied according to temporal separation (0, 2, 4, or 6) or the number of arms that occurred between the two choice arms in the sample phase sequence. On each task, once a preoperative criterion was reached, each rat was given either a DG, CA1, or control lesion and then retested. The results demonstrated that DG lesions resulted in a deficit on the spatial task but not the temporal task. In contrast, CA1 lesions resulted in a deficit on the temporal task but not the spatial task. Results suggest that the DG supports spatial pattern separation, whereas CA1 supports temporal pattern separation.

Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1

The purpose of this review is to determine whether specific subregions (dentate gyrus [DG], CA3, and CA1) of the hippocampus provide unique contributions to specific processes associated with intrinsic information processing exemplified by novelty detection, encoding, pattern separation, pattern association, pattern completion, retrieval, short-term memory and intermediate-term memory. Based on anatomical neural network organization, electrophysiology of cellular activity, lesions, early gene activation, and computational modeling, it can be shown that there exists extensive cooperation among the three subregions of the hippocampus, but there also exists reliable specificity of function for each of the subregions of the hippocampus. The primary process supported by the DG subregion of the hippocampus can be characterized by orthogonalization of sensory inputs to create a metric spatial representation. Furthermore the DG participates in conjunction with CA3 in supporting spatial pattern separation. The CA3 subregion of the hippocampus supports processes associated with spatial pattern association, spatial pattern completion, novelty detection, and short-term memory. The CA1 subregion of the hippocampus supports processes associated with temporal pattern association, temporal pattern completion, and intermediate-term memory. Furthermore, the CA3 in conjunction with CA1 supports temporal pattern separation. All the above-mentioned processes are assumed to reflect intrinsic processing of information within the hippocampus. The diversity of functions associated with the different subregions of the hippocampus suggests that one should not treat the hippocampus as a single entity, but rather that one should concentrate on elucidating further the functions of both dorsal and ventral subregions of the hippocampus and pathways that directly connect each of the subregions as well as their connections with the entorhinal cortex.

A Behavioral Assessment of Hippocampal Function Based on a Subregional Analysis

The hippocampus, a critical brain structure for navigation, context-dependent learning and episodic memory1,2,3, is composed of anatomically heterogeneous subregions. These regions differ in their anatomical inputs as well as in their internal circuitry4. A major feature of the CA3 region is its recurrent collateral circuitry, by which the CA3 pyramidal cells make excitatory synaptic contacts on each other4,5. In contrast, pyramidal cells in the CA1 region are not extensively interconnected4. Although these differences have inspired numerous theoretical models of differential processing capacities of these two regions6,7,8,9,10,11,12,13, there have been few reports of robust differences in the firing properties of CA1 and CA3 neurons in behaving animals. The most extensively studied of these properties is the spatially selective firing of hippocampal ‘place cells’1,14. Here we report that in a dynamically changing environment, in which familiar landmarks on the behavioural track and along the wall are rotated relative to each other15,16, the population representation of the environment is more coherent between the original and cue-altered environments in CA3 than in CA1. These results demonstrate a functional heterogeneity between the place cells of CA3 and CA1 at the level of neural population representations.

Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3

The prefrontal cortex and the dorsal hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.

https://www.jneurosci.org/content/jneuro/23/4/1517.full.pdf

Inah Lee

Papers

Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus

Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1

A Behavioral Assessment of Hippocampal Function Based on a Subregional Analysis

Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3

Time-dependent relationship between the dorsal hippocampus and the prefrontal cortex in spatial memory.