The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to linking across species and approaches, and suggest future directions for investigation.
Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.
Although the critical role for epigenetic mechanisms in development and cell differentiation has long been appreciated, recent evidence reveals that these mechanisms are also employed in postmitotic neurons as a means of consolidating and stabilizing cognitive-behavioral memories. In this review, we discuss evidence for an “epigenetic code” in the central nervous system that mediates synaptic plasticity, learning, and memory. We consider how specific epigenetic changes are regulated and may interact with each other during memory formation and how these changes manifest functionally at the cellular and circuit levels. We also describe a central role for mitogen-activated protein kinases in controlling chromatin signaling in plasticity and memory. Finally, we consider how aberrant epigenetic modifications may lead to cognitive disorders that affect learning and memory, and we review the therapeutic potential of epigenetic treatments for the amelioration of these conditions.
Disruptions of genes that are involved in epigenetic functions are known to be causative for several mental retardation/intellectual disability (MR/ID) syndromes. Recent work has highlighted genes with epigenetic functions as being implicated in autism spectrum disorders (ASDs) and schizophrenia (SCZ). The gene-environment interaction is an important factor of pathogenicity for these complex disorders. Epigenetic modifications offer a mechanism by which we can explain how the environment interacts with, and is able to dynamically regulate, the genome. This review aims to provide an overview of the role of epigenetic deregulation in the etiopathology for neurodevelopment disease.
Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and “ignition” of a large-scale prefronto-parietal network. The authors compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed.
Depth structure, the third dimension of object shape, is extracted from disparity, motion, texture, and shading in the optic array. Gradient-selective neurons play a key role in this process. Such neurons occur in CIP, AIP, TEs, and F5 (for first- or second-order disparity gradients), in MT/V5, in FST (for speed gradients), and in CIP and TEs (for texture gradients). Most of these regions are activated during magnetic resonance scanning in alert monkeys by comparing 3D conditions with the 2D controls for the different cues. Similarities in activation patterns of monkeys and humans tested with identical paradigms suggest that like gradient-selective neurons are found in corresponding human cortical areas. This view gains credence as the homologies between such areas become more evident. Furthermore, 3D shape-processing networks are similar in the two species, with the exception of the greater involvement of human posterior parietal cortex in the extraction of 3D shape from motion. Thus we can begin to understand how depth structure is extracted from motion, disparity, and texture in the primate brain, but the extraction of depth structure from shading and that of wire-like objects requires further scrutiny.
Guy A. Orban The Extraction of 3D Shape in the Visual System of Human and Nonhuman Primates Annual Review of Neuroscience Vol. 34: 361-388 (Volume publication date July 2011) First published online as a Review in Advance on March 29, 2011 DOI: 10.1146/annurev-neuro-061010-113819