Contrasting Roles of Neural Firing Rate and Local Field Potentials In Human Memory.

Recording the activity of neurons is a mainstay of animal memory research, while human recordings are generally limited to the activity of large ensembles of cells. The relationship between ensemble activity and neural firing rate during declarative memory processes, however, remains unclear. We recorded neurons and local field potentials (LFPs) simultaneously from the same sites in the human hippocampus and entorhinal cortex (ERC) in patients with implanted intracranial electrodes during a virtual taxi-driver task that also included a memory retrieval component. Neurons increased their firing rate in response to specific passengers or landmarks both during navigation and retrieval. Although we did not find item specificity in the broadband LFP, both theta- and gamma-band LFPs increased power to specific items on a small but significant percent of channels. These responses, however, did not correlate with item-specific neural responses. To contrast item-specific responses with process-specific responses during memory, we compared neural and LFP responses during encoding (navigation) and retrieval (associative and item-specific recognition). A subset of neurons also altered firing rates nonspecifically while subjects viewed items during encoding. interestingly, LFPs in the hippocampus and ERC increased in power nonspecifically while subjects viewed items during retrieval, more often during associative than item-recognition. Furthermore, we found no correlation between neural firing rate and broadband, theta-band, and gamma-band LFPs during process-specific responses. Our findings suggest that neuronal firing and ensemble activity can be dissociated during encoding, item-maintenance, and retrieval in the human hippocampal area, likely relating to functional properties unique to this region. (c) 2007 Wiley-Liss, Inc

Destruction of White Matter Integrity in Patients With Mild Cognitive Impairment and Alzheimer Disease

BackgroundAccumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD).ObjectiveThe aim of this research was to study the microstructural integrity of white matter in AD in vivo.MethodsGlobal fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer’s Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups.ResultsCompared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally.ConclusionsThe radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD

Perspectives on ENCODE

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.11Nsciescopu

Expanded encyclopaedias of DNA elements in the human and mouse genomes

AbstractThe human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.11Nsciescopu