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Annual Review of Neuroscience [journal]
- Translational control in synaptic plasticity and cognitive dysfunction. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.]
- Annu Rev Neurosci 2014.:17-38.
Activity-dependent changes in the strength of synaptic connections are fundamental to the formation and maintenance of memory. The mechanisms underlying persistent changes in synaptic strength in the hippocampus, specifically long-term potentiation and depression, depend on new protein synthesis. Such changes are thought to be orchestrated by engaging the signaling pathways that regulate mRNA translation in neurons. In this review, we discuss the key regulatory pathways that govern translational control in response to synaptic activity and the mRNA populations that are specifically targeted by these pathways. The critical contribution of regulatory control over new protein synthesis to proper cognitive function is underscored by human disorders associated with either silencing or mutation of genes encoding proteins that directly regulate translation. In light of these clinical implications, we also consider the therapeutic potential of targeting dysregulated translational control to treat cognitive disorders of synaptic dysfunction.
- Embodied cognition and mirror neurons: a critical assessment. [Journal Article]
- Annu Rev Neurosci 2014.:1-15.
According to embodied cognition theories, higher cognitive abilities depend on the reenactment of sensory and motor representations. In the first part of this review, we critically analyze the central claims of embodied theories and argue that the existing behavioral and neuroimaging data do not allow investigators to discriminate between embodied cognition and classical cognitive accounts, which assume that conceptual representations are amodal and symbolic. In the second part, we review the main claims and the core electrophysiological findings typically cited in support of the mirror neuron theory of action understanding, one of the most influential examples of embodied cognition theories. In the final part, we analyze the claim that mirror neurons subserve action understanding by mapping visual representations of observed actions on motor representations, trying to clarify in what sense the representations carried by these neurons can be claimed motor.
- Chemogenetic tools to interrogate brain functions. [Journal Article]
- Annu Rev Neurosci 2014.:387-407.
Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been developed for remotely controlling neuron function using small molecules that activate engineered receptors that can be targeted to cell types using genetic methods. Here we describe recent progress for approaches using genetically engineered receptors that selectively interact with small molecules. Called "chemogenetics," receptors with diverse cellular functions have been developed that facilitate the selective pharmacological control over a diverse range of cell-signaling processes, including electrical activity, for molecularly defined cell types. These tools have revealed remarkably specific behavioral physiological influences for molecularly defined cell types that are often intermingled with populations having different or even opposite functions.
- Measuring consciousness in severely damaged brains. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Annu Rev Neurosci 2014.:457-78.
Significant advances have been made in the behavioral assessment and clinical management of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms are now available to help assess consciousness levels in this challenging patient population. The success of these neuroimaging approaches as diagnostic markers is, however, intrinsically linked to understanding the relationships between consciousness and the brain. In this context, a combined theoretical approach to neuroimaging studies is needed. The promise of such theoretically based markers is illustrated by recent findings that used a perturbational approach to assess the levels of consciousness. Further research on the contents of consciousness in DOC is also needed.
- Generating human neurons in vitro and using them to understand neuropsychiatric disease. [Journal Article]
- Annu Rev Neurosci 2014.:479-501.
Recent advances in cell reprogramming enable investigators to generate pluripotent stem cells from somatic cells. These induced pluripotent cells can subsequently be differentiated into any cell type, making it possible for the first time to obtain functional human neurons in the lab from control subjects and patients with psychiatric disorders. In this review, we survey the progress made in generating various neuronal subtypes in vitro, with special emphasis on the characterization of these neurons and the identification of unique features of human brain development in a dish. We also discuss efforts to uncover neuronal phenotypes from patients with psychiatric disease and prospects for the use of this platform for drug development.
- Decoding neural representational spaces using multivariate pattern analysis. [Journal Article]
- Annu Rev Neurosci 2014.:435-56.
A major challenge for systems neuroscience is to break the neural code. Computational algorithms for encoding information into neural activity and extracting information from measured activity afford understanding of how percepts, memories, thought, and knowledge are represented in patterns of brain activity. The past decade and a half has seen significant advances in the development of methods for decoding human neural activity, such as multivariate pattern classification, representational similarity analysis, hyperalignment, and stimulus-model-based encoding and decoding. This article reviews these advances and integrates neural decoding methods into a common framework organized around the concept of high-dimensional representational spaces.
- Emotion and decision making: multiple modulatory neural circuits. [Journal Article, Research Support, N.I.H., Extramural]
- Annu Rev Neurosci 2014.:263-87.
Although the prevalent view of emotion and decision making is derived from the notion that there are dual systems of emotion and reason, a modulatory relationship more accurately reflects the current research in affective neuroscience and neuroeconomics. Studies show two potential mechanisms for affect's modulation of the computation of subjective value and decisions. Incidental affective states may carry over to the assessment of subjective value and the decision, and emotional reactions to the choice may be incorporated into the value calculation. In addition, this modulatory relationship is reciprocal: Changing emotion can change choices. This research suggests that the neural mechanisms mediating the relation between affect and choice vary depending on which affective component is engaged and which decision variables are assessed. We suggest that a detailed and nuanced understanding of emotion and decision making requires characterizing the multiple modulatory neural circuits underlying the different means by which emotion and affect can influence choices.
- Functions and dysfunctions of adult hippocampal neurogenesis. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Annu Rev Neurosci 2014.:243-62.
Adult neurogenesis, a developmental process of generating functionally integrated neurons, occurs throughout life in the hippocampus of the mammalian brain and showcases the highly plastic nature of the mature central nervous system. Significant progress has been made in recent years to decipher how adult neurogenesis contributes to brain functions. Here we review recent findings that inform our understanding of adult hippocampal neurogenesis processes and special properties of adult-born neurons. We further discuss potential roles of adult-born neurons at the circuitry and behavioral levels in cognitive and affective functions and how their dysfunction may contribute to various brain disorders. We end by considering a general model proposing that adult neurogenesis is not a cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal circuit via the continuous addition of immature, new neurons with unique properties and structural plasticity of mature neurons induced by new-neuron integration.
- The neurobiology of language beyond single words. [Journal Article, Research Support, Non-U.S. Gov't]
- Annu Rev Neurosci 2014.:347-62.
A hallmark of human language is that we combine lexical building blocks retrieved from memory in endless new ways. This combinatorial aspect of language is referred to as unification. Here we focus on the neurobiological infrastructure for syntactic and semantic unification. Unification is characterized by a high-speed temporal profile including both prediction and integration of retrieved lexical elements. A meta-analysis of numerous neuroimaging studies reveals a clear dorsal/ventral gradient in both left inferior frontal cortex and left posterior temporal cortex, with dorsal foci for syntactic processing and ventral foci for semantic processing. In addition to core areas for unification, further networks need to be recruited to realize language-driven communication to its full extent. One example is the theory of mind network, which allows listeners and readers to infer the intended message (speaker meaning) from the coded meaning of the linguistic utterance. This indicates that sensorimotor simulation cannot handle all of language processing.
- Coding and transformations in the olfactory system. [Journal Article]
- Annu Rev Neurosci 2014.:363-85.
How is sensory information represented in the brain? A long-standing debate in neural coding is whether and how timing of spikes conveys information to downstream neurons. Although we know that neurons in the olfactory bulb (OB) exhibit rich temporal dynamics, the functional relevance of temporal coding remains hotly debated. Recent recording experiments in awake behaving animals have elucidated highly organized temporal structures of activity in the OB. In addition, the analysis of neural circuits in the piriform cortex (PC) demonstrated the importance of not only OB afferent inputs but also intrinsic PC neural circuits in shaping odor responses. Furthermore, new experiments involving stimulation of the OB with specific temporal patterns allowed for testing the relevance of temporal codes. Together, these studies suggest that the relative timing of neuronal activity in the OB conveys odor information and that neural circuits in the PC possess various mechanisms to decode temporal patterns of OB input.