Opioid addiction and overdose are at record levels in the United States. This is driven, in part, by their widespread prescription for the treatment of pain, which also increased opportunity for diversion by sensation-seeking users. Despite considerable research on the neurobiology of addiction, treatment options for opioid abuse remain limited. Mood disorders, particularly depression, are often comorbid

All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward-perinatal dysphagia-is often associated

Guided by its sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine

An enduring problem in neuroscience is determining whether cases of amnesia result from eradication of the memory trace (storage impairment) or if the trace is present but inaccessible (retrieval impairment). The most direct approach to resolving this question is to quantify changes in the brain mechanisms of long-term memory (BM-LTM). This approach argues that if the amnesia is due to a retrieval

The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision

Activation of mechanosensitive ion channels underlies a variety of fundamental physiological processes that require sensation of mechanical force. Different mechanosensitive channels adapt distinctive structures and mechanotransduction mechanisms to fit their biological roles. How mechanosensitive channels work, especially in animals, has been extensively studied in the past decade. Here we review

Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional

While neurons and circuits are almost unequivocally considered to be the computational units and actuators of behavior, a complete understanding of the nervous system must incorporate glial cells. Far beyond a copious but passive substrate, glial influence is inextricable from neuronal physiology, whether during developmental guidance and synaptic shaping or through the trophic support, neurotransmitter

Cells of the oligodendrocyte lineage express a wide range of Ca2+ channels and receptors that regulate oligodendrocyte progenitor cell (OPC) and oligodendrocyte formation and function. Here we define those key channels and receptors that regulate Ca2+ signaling and OPC development and myelination. We then discuss how the regulation of intracellular Ca2+ in turn affects OPC and oligodendrocyte biology

Itch is a unique sensation that helps organisms scratch away external threats; scratching itself induces an immune response that can contribute to more itchiness. Itch is induced chemically in the peripheral nervous system via a wide array of receptors. Given the superficial localization of itch neuron terminals, cells that dwell close to the skin contribute significantly to itch. Certain mechanical

Interval timing, which operates on timescales of seconds to minutes, is distributed across multiple brain regions and may use distinct circuit mechanisms as compared to millisecond timing and circadian rhythms. However, its study has proven difficult, as timing on this scale is deeply entangled with other behaviors. Several circuit and cellular mechanisms could generate sequential or ramping activity

Sensory experience and the resulting synaptic activity within the brain are critical for the proper development of neural circuits. Experience-driven synaptic activity causes membrane depolarization and calcium influx into select neurons within a neural circuit, which in turn trigger a wide variety of cellular changes that alter the synaptic connectivity within the neural circuit. One way in which

Oligodendrocytes and Schwann cells are highly specialized glial cells that wrap axons with a multilayered myelin membrane for rapid impulse conduction. Investigators have recently identified axonal signals that recruit myelin-forming Schwann cells from an alternate fate of simple axonal engulfment. This is the evolutionary oldest form of axon-glia interaction, and its function is unknown. Recent observations

Patterns of synaptic connections in the visual system are remarkably precise. These connections dictate the receptive field properties of individual visual neurons and ultimately determine the quality of visual perception. Spontaneous neural activity is necessary for the development of various receptive field properties and visual feature maps. In recent years, attention has shifted to understanding

Infants learn language(s) with apparent ease, and the tools of modern neuroscience are providing valuable information about the mechanisms that underlie this capacity. Noninvasive, safe brain technologies have now been proven feasible for use with children starting at birth. The past decade has produced an explosion in neuroscience research examining young children's processing of language at the phonetic

The protein-only hypothesis posits that the infectious agent causing transmissible spongiform encephalopathies consists of protein and lacks any informational nucleic acids. This agent, termed prion by Stanley Prusiner, is thought to consist partly of PrP(Sc), a conformational isoform of a normal cellular protein termed PrP(C). Scientists and lay persons have been fascinated by the prion concept, and

Faces are among the most informative stimuli we ever perceive: Even a split-second glimpse of a person's face tells us his identity, sex, mood, age, race, and direction of attention. The specialness of face processing is acknowledged in the artificial vision community, where contests for face-recognition algorithms abound. Neurological evidence strongly implicates a dedicated machinery for face processing

Guiding effective movement through the environment is one of the visual system's most important functions. The pattern of motion that we see allows us to estimate our heading accurately in a variety of environments, despite the added difficulty imposed by our own eye and head movements. The cortical substrates for heading perception include the medial superior temporal area (MST) and the ventral intraparietal

Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral control that is scarcely available to consciousness. A broad spectrum of behavioral

The Wnt family of secreted proteins plays a crucial role in nervous system wiring. Wnts regulate neuronal positioning, polarization, axon and dendrite development, and synaptogenesis. These diverse roles of Wnt proteins are due not only to the large numbers of Wnt ligands and receptors but also to their ability to signal through distinct signaling pathways in different cell types and developmental

At the optic chiasm, retinal ganglion cell axons from each eye converge and segregate into crossed and uncrossed projections, a pattern critical for binocular vision. Here, we review recent findings on optic chiasm development, highlighting the specific transcription factors and guidance cues that implement retinal axon divergence into crossed and uncrossed pathways. Although mechanisms underlying

The ability of distinct anatomical circuits to generate multiple behavioral patterns is widespread among vertebrate and invertebrate species. These multifunctional neuronal circuits are the result of multistable neural dynamics and modular organization. The evidence suggests multifunctional circuits can be classified by distinct architectures, yet the activity patterns of individual neurons involved

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human central nervous system. The clinical disease course is variable, usually starts with reversible episodes of neurological disability in the third or fourth decade of life, and transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. We review data that support neurodegeneration

A task set is a configuration of cognitive processes that is actively maintained for subsequent task performance. Single-unit and brain-imaging studies have identified the neural correlates for task sets in the prefrontal cortex. Here I examine whether the neural data obtained thus far are sufficient to explain the behaviors that have been illustrated within the conceptual framework of task sets. I

Each of the descending pathways involved in motor control has a number of anatomical, molecular, pharmacological, and neuroinformatic characteristics. They are differentially involved in motor control, a process that results from operations involving the entire motor network rather than from the brain commanding the spinal cord. A given pathway can have many functional roles. This review explores to

Many major human neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), display axonal pathologies including abnormal accumulations of proteins and organelles. Such pathologies highlight damage to the axon as part of the pathogenic process and, in particular, damage to transport of cargoes through axons. Indeed, we now know that disruption

Each movement we make activates our own sensory receptors, thus causing a problem for the brain: the spurious, movement-related sensations must be discriminated from the sensory inputs that really matter, those representing our environment. Here we consider circuits for solving this problem in the primate brain. Such circuits convey a copy of each motor command, known as a corollary discharge (CD)

Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some

Elegant sensory structures in the inner ear have evolved to measure head motion. These vestibular receptors consist of highly conserved semicircular canals and otolith organs. Unlike other senses, vestibular information in the central nervous system becomes immediately multisensory and multimodal. There is no overt, readily recognizable conscious sensation from these organs, yet vestibular signals

Mitochondrial diseases (encephalomyopathies) have traditionally been ascribed to defects of the respiratory chain, which has helped researchers explain their genetic and clinical complexity. However, other mitochondrial functions are greatly important for the nervous system, including protein importation, organellar dynamics, and programmed cell death. Defects in genes controlling these functions are

Dendritic spines are the primary recipients of excitatory input in the central nervous system. They provide biochemical compartments that locally control the signaling mechanisms at individual synapses. Hippocampal spines show structural plasticity as the basis for the physiological changes in synaptic efficacy that underlie learning and memory. Spine structure is regulated by molecular mechanisms

More than three decades of research have demonstrated a role for hippocampal place cells in representation of the spatial environment in the brain. New studies have shown that place cells are part of a broader circuit for dynamic representation of self-location. A key component of this network is the entorhinal grid cells, which, by virtue of their tessellating firing fields, may provide the elements

The nervous systems of most vertebrates include both the cerebellum and structures that are architecturally similar to the cerebellum. The cerebellum-like structures are sensory structures that receive input from the periphery in their deep layers and parallel fiber input in their molecular layers. This review describes these cerebellum-like structures and compares them with the cerebellum itself.

Spike timing-dependent plasticity (STDP) as a Hebbian synaptic learning rule has been demonstrated in various neural circuits over a wide spectrum of species, from insects to humans. The dependence of synaptic modification on the order of pre- and postsynaptic spiking within a critical window of tens of milliseconds has profound functional implications. Over the past decade, significant progress has

The study of decision making spans such varied fields as neuroscience, psychology, economics, statistics, political science, and computer science. Despite this diversity of applications, most decisions share common elements including deliberation and commitment. Here we evaluate recent progress in understanding how these basic elements of decision formation are implemented in the brain. We focus on

Functional and structural neuroimaging studies of adult readers have provided a deeper understanding of the neural basis of reading, yet such findings also elicit new questions about how developing neural systems come to support this learned ability. A developmental cognitive neuroscience approach provides insights into how skilled reading emerges in the developing brain, yet also raises new methodological

The unparalleled complexity of intercellular connections in the nervous system presents requirements for high levels of both specificity and diversity for the proteins that mediate cell adhesion. Here we describe recent advances toward understanding the molecular mechanisms that underlie adhesive binding, specificity, and diversity for several well-characterized families of adhesion molecules in the

Many lesion studies report an amazing variety of deficits in behavioral functions that cannot possibly be encoded in great detail by the relatively small number of midbrain dopamine neurons. Although hoping to unravel a single dopamine function underlying these phenomena, electrophysiological and neurochemical studies still give a confusing, mutually exclusive, and partly contradictory account of dopamine's

The blood brain barrier (BBB) evolved to preserve the microenvironment of the highly excitable neuronal cells to allow for action potential generation and propagation. Intricate molecular interactions between two main cell types, the neurons and the glial cells, form the underlying basis of the critical functioning of the nervous system across species. In invertebrates, interactions between neurons

Significant advancements have been made in the past century regarding the neuronal control of feeding behavior and energy expenditure. The effects and mechanisms of action of various peripheral metabolic signals on the brain have become clearer. Molecular and genetic tools for visualizing and manipulating individual components of brain homeostatic systems in combination with neuroanatomical, electrophysiological

Wallerian degeneration (WD) is the set of molecular and cellular events by which degenerating axons and myelin are cleared after injury. Why WD is rapid and robust in the PNS but slow and incomplete in the CNS is a longstanding mystery. Here we review current work on the mechanisms of WD with an emphasis on deciphering this mystery and on understanding whether slow WD in the CNS could account for the

The chemical senses-smell and taste-allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in

Mechanical stimuli generated by head movements and changes in sound pressure are detected by hair cells with amazing speed and sensitivity. The mechanosensitive organelle, the hair bundle, is a highly elaborated structure of actin-based stereocilia arranged in precise rows of increasing height. Extracellular linkages contribute to its cohesion and convey forces to mechanically gated channels. Channel

The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provides the substrate for cognition, whereas improper formation or function of these synapses

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 prevailing view of medial temporal lobe (MTL) function has two principal elements: first, that the MTL subserves memory but not perception, and second, that the many anatomically distinctive parts of the MTL function together in the service of declarative memory. Recent neuropsychological studies have, however, challenged both opinions. First, studies in rodents, nonhuman primates, and humans suggest

The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy. The dynamic nature of these mutations provided an explanation for the variable phenotype expressivity within a family. Beyond diagnosis and genetic

Damage to orbitofrontal cortex (OFC) produces an unusual pattern of deficits. Patients have intact cognitive abilities but are impaired in making everyday decisions. Here we review anatomical, neuropsychological, and neurophysiological evidence to determine the neuronal mechanisms that might underlie these impairments. We suggest that OFC plays a key role in processing reward: It integrates multiple

A mechanistic understanding of attention is necessary for the elucidation of the neurobiological basis of conscious experience. This chapter presents a framework for thinking about attention that facilitates the analysis of this cognitive process in terms of underlying neural mechanisms. Four processes are fundamental to attention: working memory, top-down sensitivity control, competitive selection

Although dendrite arborization patterns are hallmarks of neuronal type and critical determinants of neuronal function, how dendritic arbors take shape is still largely unknown. Transcription factors play important roles in specifying neuronal types and have a profound influence on dendritic arbor size and complexity. The space that a dendritic arbor occupies is determined largely by a combination of

Ventral tegmental area (VTA) neuron firing precedes behaviors elicited by reward-predictive sensory cues and scales with the magnitude and unpredictability of received rewards. These patterns are consistent with roles in the performance of learned appetitive behaviors and in positive reinforcement, respectively. The VTA includes subpopulations of neurons with different afferent connections, neurotransmitter

Copper and iron are transition elements essential for life. These metals are required to maintain the brain's biochemistry such that deficiency or excess of either copper or iron results in central nervous system disease. This review focuses on the inherited disorders in humans that directly affect copper or iron homeostasis in the brain. Elucidation of the molecular genetic basis of these rare disorders

Whereas the central nervous system (CNS) usually cannot regenerate, peripheral nerves regenerate spontaneously after injury because of a permissive environment and activation of the intrinsic growth capacity of neurons. Functional regeneration requires axon regrowth and remyelination of the regenerated axons by Schwann cells. Multiple factors including neurotrophic factors, extracellular matrix (ECM)

Navigation first requires accurate perception of one's spatial orientation within the environment, which consists of knowledge about location and directional heading. Cells within several limbic system areas of the mammalian brain discharge allocentrically as a function of the animal's directional heading, independent of the animal's location and ongoing behavior. These cells are referred to as head

The function of any neural circuit is governed by connectivity of neurons in the circuit and the computations performed by the neurons. Recent research on retinal function has substantially advanced understanding in both areas. First, visual information is transmitted to the brain by at least 17 distinct retinal ganglion cell types defined by characteristic morphology, light response properties, and

In excitatory neurons, most glutamatergic synapses are made on the heads of dendritic spines, each of which houses the postsynaptic terminal of a single glutamatergic synapse. We review recent studies demonstrating in vivo that spines are motile and plastic structures whose morphology and lifespan are influenced, even in adult animals, by changes in sensory input. However, most spines that appear in

Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be

The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system

The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide variety of inflammatory conditions, and NGF-neutralizing

System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm