Michael M. Merzenich

Bio: Michael M. Merzenich is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Auditory cortex & Receptive field. The author has an hindex of 112, co-authored 316 publications receiving 50700 citations. Previous affiliations of Michael M. Merzenich include Johns Hopkins University School of Medicine & Johns Hopkins University.

Model of autism: increased ratio of excitation/inhibition in key neural systems

Abstract: Autism is a severe neurobehavioral syndrome, arising largely as an inherited disorder, which can arise from several diseases. Despite recent advances in identifying some genes that can cause autism, its underlying neurological mechanisms are uncertain. Autism is best conceptualized by considering the neural systems that may be defective in autistic individuals. Recent advances in understanding neural systems that process sensory information, various types of memories and social and emotional behaviors are reviewed and compared with known abnormalities in autism. Then, specific genetic abnormalities that are linked with autism are examined. Synthesis of this information leads to a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems. The model further postulates that the increased ratio of excitation/inhibition can be caused by combinatorial effects of genetic and environmental variables that impinge upon a given neural system. Furthermore, the model suggests potential therapeutic interventions.

CORTICAL PLASTICITY: From Synapses to Maps

Abstract: It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood. In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.

Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys

Abstract: This study was undertaken to document plastic changes in the functional topography of primary motor cortex (M1) that are generated in motor skill learning in the normal, intact primate. Intracortical microstimulation mapping techniques were used to derive detailed maps of the representation of movements in the distal forelimb zone of M1 of squirrel monkeys, before and after behavioral training on two different tasks that differentially encouraged specific sets of forelimb movements. After training on a small-object retrieval task, which required skilled use of the digits, their evoked-movement digit representations expanded, whereas their evoked-movement wrist/forearm representational zones contracted. These changes were progressive and reversible. In a second motor skill exercise, a monkey pronated and supinated the forearm in a key (eyebolt)-turning task. In this case, the representation of the forearm expanded, whereas the digit representational zones contracted. These results show that M1 is alterable by use throughout the life of an animal. These studies also revealed that after digit training there was an areal expansion of dual-response representations, that is, cortical sectors over which stimulation produced movements about two or more joints. Movement combinations that were used more frequently after training were selectively magnified in their cortical representations. This close correspondence between changes in behavioral performance and electrophysiologically defined motor representations indicates that a neurophysiological correlate of a motor skill resides in M1 for at least several days after acquisition. The finding that cocontracting muscles in the behavior come to be represented together in the cortex argues that, as in sensory cortices, temporal correlations drive emergent changes in distributed motor cortex representations.

Somatosensory cortical map changes following digit amputation in adult monkeys

Abstract: The cortical representations ofthe hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2-8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Suc­ cessive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and pal­ mar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et aI., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representa­ tions (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically main­ tained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500-700 JIm on either side of the initial boundaries of the representation of the amputated digits. More dis­ tant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every

Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys

Abstract: Previous studies have shown that the tonotopic organization of primary auditory cortex is altered subsequent to restricted cochlear lesions (Robertson and Irvine, 1989) and that the topographic reorganization of the primary somatosensory cortex is correlated with changes in the perceptual acuity of the animal (Recanzone et al., 1992a-d). Here we report an increase in the cortical area of representation of a restricted frequency range in primary auditory cortex of adult owl monkeys that is correlated with the animal's performance at a frequency discrimination task. Monkeys trained for several weeks to discriminate small differences in the frequency of sequentially presented tonal stimuli revealed a progressive improvement in performance with training. At the end of the training period, the tonotopic organization of Al was defined by recording multiple-unit responses at 70-258 cortical locations. These responses were compared to those derived from three normal monkeys and from two monkeys that received the same auditory stimuli but that were engaged in a tactile discrimination task. The cortical representation, the sharpness of tuning, and the latency of the response were greater for the behaviorally relevant frequencies of trained monkeys when compared to the same frequencies of control monkeys. The cortical area of representation was the only studied parameter that was correlated with behavioral performance. These results demonstrate that attended natural stimulation can modify the tonotopic organization of Al in the adult primate, and that this alteration is correlated with changes in perceptual acuity.

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

Abstract: 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。

Digital Natives, Digital Immigrants

Abstract: It is amazing to me how in all the hoopla and debate these days about the decline of education in the US we ignore the most fundamental of its causes. Our students have changed radically. Today’s students are no longer the people our educational system was designed to teach. Today’s students have not just changed incrementally from those of the past, nor simply changed their slang, clothes, body adornments, or styles, as has happened between generations previously. A really big discontinuity has taken place. One might even call it a “singularity” – an event which changes things so fundamentally that there is absolutely no going back. This so-called “singularity” is the arrival and rapid dissemination of digital technology in the last decades of the 20 th century.

The self-organizing map

Abstract: The self-organized map, an architecture suggested for artificial neural networks, is explained by presenting simulation experiments and practical applications. The self-organizing map has the property of effectively creating spatially organized internal representations of various features of input signals and their abstractions. One result of this is that the self-organization process can discover semantic relationships in sentences. Brain maps, semantic maps, and early work on competitive learning are reviewed. The self-organizing map algorithm (an algorithm which order responses spatially) is reviewed, focusing on best matching cell selection and adaptation of the weight vectors. Suggestions for applying the self-organizing map algorithm, demonstrations of the ordering process, and an example of hierarchical clustering of data are presented. Fine tuning the map by learning vector quantization is addressed. The use of self-organized maps in practical speech recognition and a simulation experiment on semantic mapping are discussed. >

Distributed Hierarchical Processing in the Primate Cerebral Cortex

Abstract: In recent years, many new cortical areas have been identified in the macaque monkey. The number of identified connections between areas has increased even more dramatically. We report here on (1) a summary of the layout of cortical areas associated with vision and with other modalities, (2) a computerized database for storing and representing large amounts of information on connectivity patterns, and (3) the application of these data to the analysis of hierarchical organization of the cerebral cortex. Our analysis concentrates on the visual system, which includes 25 neocortical areas that are predominantly or exclusively visual in function, plus an additional 7 areas that we regard as visual-association areas on the basis of their extensive visual inputs. A total of 305 connections among these 32 visual and visual-association areas have been reported. This represents 31% of the possible number of pathways if each area were connected with all others. The actual degree of connectivity is likely to be closer to 40%. The great majority of pathways involve reciprocal connections between areas. There are also extensive connections with cortical areas outside the visual system proper, including the somatosensory cortex, as well as neocortical, transitional, and archicortical regions in the temporal and frontal lobes. In the somatosensory/motor system, there are 62 identified pathways linking 13 cortical areas, suggesting an overall connectivity of about 40%. Based on the laminar patterns of connections between areas, we propose a hierarchy of visual areas and of somatosensory/motor areas that is more comprehensive than those suggested in other recent studies. The current version of the visual hierarchy includes 10 levels of cortical processing. Altogether, it contains 14 levels if one includes the retina and lateral geniculate nucleus at the bottom as well as the entorhinal cortex and hippocampus at the top. Within this hierarchy, there are multiple, intertwined processing streams, which, at a low level, are related to the compartmental organization of areas V1 and V2 and, at a high level, are related to the distinction between processing centers in the temporal and parietal lobes. However, there are some pathways and relationships (about 10% of the total) whose descriptions do not fit cleanly into this hierarchical scheme for one reason or another. In most instances, though, it is unclear whether these represent genuine exceptions to a strict hierarchy rather than inaccuracies or uncertainities in the reported assignment.

From Neurons to Neighborhoods: The Science of Early Childhood Development

Abstract: How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.