141-160 of 185 Results

Article

Regulation of Gonadotropins  

Daniel J. Bernard, Yining Li, Chirine Toufaily, and Gauthier Schang

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are glycoproteins produced by gonadotrope cells of the anterior pituitary gland. The two hormones act on somatic cells of the gonads in both males and females to regulate fundamental aspects of reproductive physiology, including gametogenesis and steroidogenesis. In males, LH stimulates testosterone production and sperm maturation. FSH also regulates spermatogenesis, though the importance of the hormone in this process differs across species. In females, FSH stimulates ovarian follicle maturation. Follicles are structures composed of oocytes surrounded by two types of somatic cells, granulosa and theca cells. FSH stimulates granulosa cells to proliferate and to increase their production of the aromatase enzyme. LH stimulates theca cells to make androgens, which are converted into estrogens by aromatase in granulosa cells. A surge of LH also stimulates ovulation of mature follicles. Gonadotropin-releasing hormone (GnRH) from the brain is the principal stimulator of gonadotropin synthesis and secretion from the pituitary. The sex steroids (androgens and estrogens) that are produced by the gonads in response to the gonadotropins feedback to the brain and pituitary gland. In the brain, these hormones usually slow the release of GnRH through a process called negative feedback, which in turn leads to decreases in FSH and LH. The steroids also modulate the sensitivity of the pituitary to GnRH in addition to directly regulating expression of the genes that encode the gonadotropin subunits. These effects are gene- and species-specific. In females, estrogens also have positive feedback actions in the brain and pituitary in a reproductive cycle stage-dependent manner. This positive feedback promotes GnRH and LH release, leading to the surge of LH that triggers ovulation. The gonadotropins are dimeric proteins. FSH and LH share a common α-subunit but have hormone-specific subunits, FSHβ and LHβ. The β subunits provide a means for differential regulation and action of the two hormones. In the case of FSH, there is a second gonadal feedback system that specifically regulates the FSHβ subunit. The gonads produce proteins in the transforming growth factor β (TGFβ) family called inhibins, which come in two forms (inhibin A and inhibin B). The ovary produces both inhibins whereas the testes make inhibin B alone. Inhibins selectively suppress FSH synthesis and secretion, without affecting LH. The pituitary produces additional TGFβ proteins called activins, which are structurally related to inhibins. Activins, however, stimulate FSH synthesis by promoting transcription of the FSHβ subunit gene. Inhibins act as competitive receptor antagonists, binding to activin receptors and blocking activin action, and thereby leading to decreases in FSH. Together, GnRH, sex steroids, activins, and inhibins modulate and coordinate gonadotropin production and action to promote proper gonadal function and fertility.

Article

Regulators and Integration of Peripheral Signals  

Michelle T. Foster

In mammals, reproductive function is closely regulated by energy availability. It is influenced by both extremes of nutrition, too few calories (undernutrition) and an excessive amount of calories (obesity). Atypical decreases or increases in weight can have adverse effects on the reproductive axis. This includes suppression of reproductive function, decreases in ovarian cyclicity, reduction in fertility, anovulation, and dysregulation of spermatogenesis. The balance between energy regulation and reproduction is supervised by a complex system comprised of the brain and peripheral tissues. The brain senses and integrates various systemic and central signals that are indicative of changes in body physiology and energy status. This occurs via numerous factors, including metabolic hormones and nutrients. Adipokines, endocrine factors primarily secreted by white adipose tissue, and adipose tissue related cytokines (adipocytokines) contribute to the regulation of maturity, fertility, and reproduction. Indeed, some adipokines play a fundamental role in reproductive disorders. The brain, predominantly the hypothalamus, is responsible for linking adipose-derived signals to pathways controlling reproductive processes. Gonadotropin-releasing hormone (GnRH) cells in the hypothalamus are fundamental in relaying adipose-derived signals to the pituitary–gonadal axis, which consequently controls reproductive processes. Leptin, adiponectin, apelin, chermin, resistin, and visfatin are adipokines that regulate reproductive events via the brain.

Article

Retinal Mechanisms for Motion Detection  

Mathew T. Summers, Malak El Quessny, and Marla B. Feller

Motion is a key feature of the sensory experience of visual animals. The mammalian retina has evolved a number of diverse motion sensors to detect and parse visual motion into behaviorally relevant neural signals. Extensive work has identified retinal outputs encoding directional and nondirectional motion, and the intermediate circuitry underlying this tuning. Detailed circuit mechanism investigation has established retinal direction selectivity in particular as a model system of neural computation.

Article

The Role of Microglia in Brain Aging: A Focus on Sex Differences  

Jeffrey S. Darling, Kevin Sanchez, Andrew D. Gaudet, and Laura K. Fonken

Microglia, the primary innate immune cells of the brain, are critical for brain maintenance, inflammatory responses, and development in both sexes across the lifespan. Indeed, changes in microglia form and function with age have physiological and behavioral implications. Microglia in the aged brain undergo functional changes that enhance responses to diverse environmental insults. The heightened sensitivity of aged microglia amplifies proinflammatory responses, including increased production of proinflammatory cytokines and chemokines, elevated danger signals, and deficits in debris clearance. Elevated microglia activity and neuroinflammation culminate in neuropathology, including increased risk for neurodegenerative diseases and cognitive decline. Importantly, there are sex differences in several age-related neuroinflammatory pathologies. Microglia coordinate sex-dependent development within distinct brain structures and behaviors and are, in turn, sensitive to sex-specific hormones. This implies that microglia may confer differential disease risk by undergoing sex-specific changes with age. Understanding how aging and sex influence microglial function may lead to targeted therapies for age- and sex-associated diseases and disorders.

Article

The Role of Neuroinflammation in the Response to Spinal Cord Injury  

Olivia H. Bodart, Ethan P. Glaser, Steven M. MacLean, Meifan A. Chen, and John C. Gensel

Spinal cord injury (SCI) is a life-altering event for which there is no treatment. Depending on injury location and severity, the breadth of the effects can go far past simple mobility. Primary mechanical trauma triggers a variety of secondary cellular events that exacerbate tissue loss as well as facilitate endogenous repair. A large focus of SCI research is on understanding the pathophysiological mechanisms through which these secondary responses contribute to morbidities associated with SCI. Neuroinflammation, a common response to central nervous system (CNS) insult, is central to the secondary injury cascade. In the context of SCI, the inflammatory response plays a contradictory role in recovery; immune cells release both pro- and anti-inflammatory cytokines at the injury site and clear debris while also causing damage to spared tissue. The major innate and adaptive immune cells that respond to SCI are neutrophils, astrocytes, microglia/macrophages, B cells, and T cells. For each cell type, the timing of the cellular response (in both human and rodent models of SCI), the potential role each cell type plays in the pathophysiology of injury, and the therapeutic implications of targeting each cell type for SCI recovery are discussed.

Article

The Role of Oxytocin and Vasopressin in the Neural Regulation of Social Behavior  

Heather K. Caldwell

Within the central nervous system, the neuropeptides oxytocin and vasopressin are key regulators of social behavior. While their effects can be nuanced, data suggest that they can influence behavior at multiple levels, including an individual’s personality/temperament, their social interactions in smaller groups (or one-on-one interactions), and their behavior in larger groups. At a mechanistic level, oxytocin and vasopressin help to integrate complex information—including aspects of an animal’s external and internal state—in order to shape behavioral output. Oxytocin and vasopressin help to modulate behaviors that bring animals together (i.e., cooperative behaviors) as well as behaviors that keep animals apart (i.e., competitive behaviors), with the modulatory effects often being species-, sex-, and context-dependent. While there continues to be extensive study of the function of these nonapeptides within individual brain nuclei, over the last two decades behavioral neuroendocrinologists have also made great strides in exploring their roles within larger brain networks that help to regulate social behavior. Looking forward, work on oxytocin and vasopressin will continue to shed light on how the neural regulation of social behaviors are similar, and/or dissimilar, within and between species and sexes, as well as provide insights into the neural chemistry that underlies behavioral differences in neurotypical and neurodivergent individuals.

Article

Role of Puberty on Adult Behaviors  

Kristen Delevich and Linda Wilbrecht

Puberty onset marks the beginning of adolescence and an organism’s transition to adulthood. Across species, adolescence is a dynamic period of maturation for brain and behavior. Pubertal processes, including the increase in gonadal hormone production, or gonadarche, can influence a broad array of neural processes and circuits to ultimately shape adult behavior. Decades of research in rodent models have shown that gonadal hormones at puberty promote adult-typical patterns of behavior across social, affective, and cognitive realms. Importantly, hormonal activation of sex-specific patterns of adult behavior relies on sexual differentiation of the brain around the time of birth, mediated by testicular hormones in males – and lack thereof in females. While it was originally believed that gonadal hormones play a purely activational role at puberty, studies in the early 21st century provide examples where the timing and relative levels of gonadal hormones exert long-lasting, or organizational effects on brain and behavior. In this way, adolescent exposure to gonadal hormones can orchestrate brain and body changes in unison and in some cases tune how the brain responds to gonadal hormones in adulthood. Notably, many of the effects of puberty on behavior may occur indirectly by altering sensitivity to environmental events and an organism’s ability to respond to or learn from experience. These insights from the animal literature provide a framework for understanding how puberty may influence the maturation of complex behaviors and modify risk or resilience to mental health disorders during human adolescence. In sum, puberty interacts with genetics, early life organizational effects of gonadal hormones, experience, and learning processes to shape behavior in adulthood.

Article

Role of Sex Hormones on Pain  

Dayna L. Averitt, Rebecca S. Hornung, and Anne Z. Murphy

The modulatory influence of sex hormones on acute pain, chronic pain disorders, and pain management has been reported for over seven decades. The effect of hormones on pain is clearly evidenced by the multitude of chronic pain disorders that are more common in women, such as headache and migraine, temporomandibular joint disorder, irritable bowel syndrome, chronic pelvic pain, fibromyalgia, rheumatoid arthritis, and osteoarthritis. Several of these pain disorders also fluctuate in pain intensity over the menstrual cycle, including headache and migraine and temporomandibular joint disorder. The sex steroid hormones (estrogen, progesterone, and testosterone) as well as some peptide hormones (prolactin, oxytocin, and vasopressin) have been linked to pain by both clinical and preclinical research. Progesterone and testosterone are widely accepted as having protective effects against pain, while the literature on estrogen reports both exacerbation and attenuation of pain. Prolactin is reported to trigger pain, while oxytocin and vasopressin have analgesic properties in both sexes. Only in the last two decades have neuroscientists begun to unravel the complex anatomical and molecular mechanisms underlying the direct effects of sex hormones and mechanisms have been reported in both the central and peripheral nervous systems. Mechanisms include directly or indirectly targeting receptors and ion channels on sensory neurons, activating pain excitatory or pain inhibitory centers in the brain, and reducing inflammatory mediators. Despite recent progress, there remains significant controversy and challenges in the field and the seemingly pleiotropic role estrogen plays on pain remains ambiguous. Current knowledge of the effects of sex hormones on pain has led to the burgeoning of gender-based medicine, and gaining further insight will lead to much needed improvement in pain management in women.

Article

Sensing Polarized Light in Insects  

Thomas F. Mathejczyk and Mathias F. Wernet

Evolution has produced vast morphological and behavioral diversity amongst insects, including very successful adaptations to a diverse range of ecological niches spanning the invasion of the sky by flying insects, the crawling lifestyle on (or below) the earth, and the (semi-)aquatic life on (or below) the water surface. Developing the ability to extract a maximal amount of useful information from their environment was crucial for ensuring the survival of many insect species. Navigating insects rely heavily on a combination of different visual and non-visual cues to reliably orient under a wide spectrum of environmental conditions while avoiding predators. The pattern of linearly polarized skylight that results from scattering of sunlight in the atmosphere is one important navigational cue that many insects can detect. Here we summarize progress made toward understanding how different insect species sense polarized light. First, we present behavioral studies with “true” insect navigators (central-place foragers, like honeybees or desert ants), as well as insects that rely on polarized light to improve more “basic” orientation skills (like dung beetles). Second, we provide an overview over the anatomical basis of the polarized light detection system that these insects use, as well as the underlying neural circuitry. Third, we emphasize the importance of physiological studies (electrophysiology, as well as genetically encoded activity indicators, in Drosophila) for understanding both the structure and function of polarized light circuitry in the insect brain. We also discuss the importance of an alternative source of polarized light that can be detected by many insects: linearly polarized light reflected off shiny surfaces like water represents an important environmental factor, yet the anatomy and physiology of underlying circuits remain incompletely understood.

Article

Sensing the Environment With Whiskers  

Mathew H. Evans, Michaela S.E. Loft, Dario Campagner, and Rasmus S. Petersen

Whiskers (vibrissae) are prominent on the snout of many mammals, both terrestrial and aquatic. The defining feature of whiskers is that they are rooted in large follicles with dense sensory innervation, surrounded by doughnut-shaped blood sinuses. Some species, including rats and mice, have elaborate muscular control of their whiskers and explore their environment by making rhythmic back-and-forth “whisking” movements. Whisking movements are purposefully modulated according to specific behavioral goals (“active sensing”). The basic whisking rhythm is controlled by a premotor complex in the intermediate reticular formation. Primary whisker neurons (PWNs), with cell bodies in the trigeminal ganglion, innervate several classes of mechanoreceptive nerve endings in the whisker follicle. Mechanotransduction involving Piezo2 ion channels establishes the fundamental physical signals that the whiskers communicate to the brain. PWN spikes are triggered by mechanical forces associated with both the whisking motion itself and whisker-object contact. Whisking is associated with inertial and muscle contraction forces that drive PWN activity. Whisker-object contact causes whiskers to bend, and PWN activity is driven primarily by the associated rotatory force (“bending moment”). Sensory signals from the PWNs are routed to many parts of the hindbrain, midbrain, and forebrain. Parallel ascending pathways transmit information about whisker forces to sensorimotor cortex. At each brainstem, thalamic, and cortical level of these pathways, there are one or more maps of the whisker array, consisting of cell clusters (“barrels” in the primary somatosensory cortex) whose spatial arrangement precisely mirrors that of the whiskers on the snout. However, the overall architecture of the whisker-responsive regions of the brain system is best characterized by multilevel sensory-motor feedback loops. Its intriguing biology, in combination with advantageous properties as a model sensory system, has made the whisker system the platform for seminal insights into brain function.

Article

The Sensory World of the Naked Mole-Rat  

Thomas J. Park

Naked mole-rats are subterranean mammals that are native to equatorial east Africa including Ethiopia, Somalia, and Kenya. They are unusual among subterranean mammals in that they live in very large colonies where many respiring animals deplete oxygen and overproduce carbon dioxide. Some of their sensory traits, such as poor vision and hearing, are considered typical of subterranean mammals. However, naked mole-rats display three sensory traits that are unusual even among subterranean mammals. First, they possess a sensitive sensory array of body vibrissae on their otherwise furless bodies. Second, they have a greatly reduced sense of inflammatory and chemical pain, but express acute mechanical and thermal pain. Third, naked mole-rats, and likely other African mole-rat species, are the only rodents known that show no postbirth growth of the vomeronasal organ, an organ associated with sensing pheromones. These sensory traits, along with extreme tolerance to hypoxia and resistance to cancer, make the naked mole-rat an important animal model for studying sensory systems as well as in multiple other scientific fields.

Article

Sex-Specific Regulation of Peripheral and Central Immune Responses  

Sabra L. Klein and Jaclyn M. Schwarz

Sex is a biological variable that affects immune responses to both self and foreign antigens (e.g., microbial infections) in the central nervous system (CNS) as well as in peripheral organs. The sex of an individual is defined by the differential determination of the sex chromosomes, the organization of the reproductive organs, and the subsequent sex steroid hormone levels in males and females. Sex is distinct from gender, which includes self-identification as being a male or female as well as behaviors and activities that are determined by society or culture in humans. Male and female differences in immunological responses may be influenced by both sex and gender, with sex contributing to the physiological and anatomical differences that influence exposure, recognition, clearance, and even transmission of microbes in males and females. By contrast, gender may reflect behaviors that influence exposure to microbes, access to health care, or health-seeking behaviors that indirectly affect the course of infection in males and females. Though both sex and gender influence the immune response, the focus of this article is the biological factors that influence immunological differences between the sexes in both the CNS and peripheral tissues to alter the course of diseases across the life span.

Article

Sexual Behavior in Females from a Neuroendocrine Perspective  

Donald Pfaff

Understanding of the brain mechanisms regulating reproductive behaviors in female laboratory animals has been aided greatly by our knowledge of estrogen receptors in the brain. Hypothalamic neurons that express the gene for estrogen receptor-alpha regulate activity in the neural circuit for the simplest female reproductive response, lordosis behavior. In turn, many of the neurotransmitter inputs to the critical hypothalamic neurons have been studied using electrophysiological and neurochemical techniques. The upshot of all of these studies is that lordosis behavior presents the best understood set of mechanisms for any mammalian behavior.

Article

Sexual Behavior in Males From a Neuroendocrine Perspective  

Jacques Balthazart and Gregory F. Ball

It is well established that testosterone from testicular origin plays a critical role in the activation of male sexual behavior in most, if not all, vertebrate species. These effects take place to a large extent in the preoptic area although other brain sites are obviously also implicated. In its target areas, testosterone is actively metabolized either into estrogenic and androgenic steroids that have specific behavioral effects or into inactive metabolites. These transformations either amplify the behavioral activity of testosterone or, alternatively, metabolism to an inactive compound dissipates any biological effect. Androgens and estrogens then bind to nuclear receptors that modulate the transcription of specific genes. This process is controlled by a variety of co-activators and co-repressors that, respectively, enhance or inhibit these transcriptional processes. In addition, recent work has shown that the production of estrogens by brain aromatase can be modulated within minutes by changes in neural activity and that these rapid changes in neuroestrogen production impact sexual behavior, in particular sexual motivation within the same time frame. Estrogens thus affect specific aspects of male sexual behavior in two different time frames via two types of mechanisms that are completely different. Multiple questions remain open concerning the cellular brain mechanisms that mediate testosterone action on male sexual behavior.

Article

Single Neuron Computational Modeling  

Yeonjoo Yoo and Fabrizio Gabbiani

Computational modeling is essential to understand how the complex dendritic structure and membrane properties of a neuron process input signals to generate output signals. Compartmental models describe how inputs, such as synaptic currents, affect a neuron’s membrane potential and produce outputs, such as action potentials, by converting membrane properties into the components of an electrical circuit. The simplest such model consists of a single compartment with a leakage conductance which represents a neuron having spatially uniform membrane potential and a constant conductance summarizing the combined effect of every ion flowing across the neuron’s membrane. The Hodgkin-Huxley model introduces two additional active channels; the sodium channel and the delayed rectifier potassium channel whose associated conductances change depending on the membrane potential and that are described by an additional set of three nonlinear differential equations. Since its conception in 1952, many kinds of active channels have been discovered with a variety of characteristics that can successfully be modeled within the same framework. As the membrane potential varies spatially in a neuron, the next refinement consists in describing a neuron as an electric cable to account for membrane potential attenuation and signal propagation along dendritic or axonal processes. A discrete version of the cable equation results in compartments with possibly different properties, such as different types of ion channels or spatially varying maximum conductances to model changes in channel densities. Branching neural processes such as dendrites can be modeled with the cable equation by considering the junctions of cables with different radii and electrical properties. Single neuron computational models are used to investigate a variety of topics and reveal insights that cannot be evidenced directly by experimental observation. Studies on action potential initiation and on synaptic integration provide prototypical examples illustrating why computational models are essential. Modeling action potential initiation constrains the localization and density of channels required to reproduce experimental observations, while modeling synaptic integration sheds light on the interaction between the morphological and physiological characteristics of dendrites. Finally, reduced compartmental models demonstrate how a simplified morphological structure supplemented by a small number of ion channel-related variables can provide clear explanations about complex intracellular membrane potential dynamics.

Article

Somatosensory Specializations in Mammals  

Jon H. Kaas

Early mammals were small with little neocortex that included a somatosensory system with a mediolateral strip of primary somatosensory cortex and three or four adjoining somatosensory fields. As early mammals radiated out and adapted to local environments, their somatosensory systems adjusted and became specialized in many ways. Most of these specializations were most obvious as disproportionally enlarged representations of important sensory surfaces of the skin in primary somatosensory cortex. These enlarged representations included those of the bill of the duckbilled platypus, the nose of the star-nosed mole, the teeth and tongue of monkeys, the glabrous hand of raccoons, the wing of bats, and the tactile tail of some monkeys. These and other specializations enhanced the ability of these mammals to adapt to their environments and to precisely evaluate relevant sensory events and make appropriate behavioral adjustments.

Article

Somatosensory System Organization in Mammals and Response to Spinal Injury  

Corinna Darian-Smith and Karen Fisher

Spinal cord injury (SCI) affects well over a million people in the United States alone, and its personal and societal costs are huge. This article provides a current overview of the organization of somatosensory and motor pathways, in the context of hand/paw function in nonhuman primate and rodent models of SCI. Despite decades of basic research and clinical trials, therapeutic options remain limited. This is largely due to the fact that (i) spinal cord structure and function is very complex and still poorly understood, (ii) there are many species differences which can make translation from the rodent to primate difficult, and (iii) we are still some way from determining the detailed multilevel pathway responses affecting recovery. There has also been little focus, until recently, on the sensory pathways involved in SCI and recovery, which are so critical to hand function and the recovery process. The potential for recovery in any individual depends on many factors, including the location and size of the injury, the extent of sparing of fiber tracts, and the post-injury inflammatory response. There is also a progression of change over the first weeks and months that must be taken into account when assessing recovery. There are currently no good biomarkers of recovery, and while axon terminal sprouting is frequently used in the experimental setting as an indicator of circuit remodeling and “recovery,” the correlation between sprouting and functional recovery deserves scrutiny.

Article

Spatial Cognition in Rodents  

Freyja Ólafsdóttir

Wayfinding, like other related spatial cognitive abilities, is a core function of all mobile animals. The past 50 years have a seen a plethora of research devoted to elucidating the neural basis of this function. This research has led to the identification of neuronal cell types—many of which can be found within the hippocampal area and afferent brain regions—that encode different spatial variables and together are thought to provide animals with a so-called “cognitive map.” Moreover, seminal research carried out over the past decade has identified a neural activity event—known as “replay”—that is thought to consolidate newly formed cognitive maps, so to commit them to long-term storage and support planning of goal-directed navigational trajectories in familiar, and perhaps novel, environments. Finally, this hippocampal spatial coding scheme has in recent years been postulated to extend to nonspatial domains, including episodic memory, suggesting it may play a general role in knowledge creation.

Article

Statistics, Computation, and Coding in the Retina  

Gregory Schwartz

One of the most common ways to approach descriptions of the function of brains is with the language of computation. Neuroscientists often speak about what the brain computes and how it performs the computation using biological hardware. Theories of neural computation in most parts of the central nervous system of vertebrates are difficult to test in satisfying ways because often only partial information is available. Computations can be distributed over millions of neurons and vast regions of the brain, and the definitions of the computations themselves are often either abstract or lack a compelling, quantitative, causal link to a specific behavior. Although the vertebrate retina is a highly complex part of the central nervous system comprising approximately 150 different cell types, studying computation in the retina has certain advantages that have enabled the field to lead the way in some disciplines of computational neuroscience. These advantages include advanced knowledge of cell types, the repeating “mosaic” structure of retinal circuits, the ability to control precisely the full input (spatiotemporal patterns of light) while recording the full output (retinal ganglion cell spikes), and quantitative links to certain innate visual behaviors. Through the lens of statistics, many retinal computations can be framed as measurements of properties of probability distributions. The ways evolution has found to make these measurements with biological components are both elegant in their simplicity and powerful in their flexibility, in many cases far exceeding the sophistication of modern human-made digital imaging technology. Fast adaptation to both the mean and the variance of time-varying light distributions allows the retina to encode the enormous dynamic range of natural images within the limited dynamic range of neurons. Signal and noise distributions are estimated and combined in ways approaching theoretical limits. Objects are localized with precision far exceeding individual receptive fields by using a form of triangulation. Predictive information about motion statistics is represented in the population code. These examples and others enable analysis of retinal computation with tools from computer science, engineering, statistics, and information theory, serving as a model for computational neuroscience.

Article

Stereopsis and Depth Perception  

Andrew J. Parker

Humans and some animals can use their two eyes in cooperation to detect and discriminate parts of the visual scene based on depth. Owing to the horizontal separation of the eyes, each eye obtains a slightly different view of the scene in front of the head. These small differences are processed by the nervous system to generate a sense of binocular depth. As humans, we experience an impression of solidity that is fully three-dimensional; this impression is called stereopsis and is what we appreciate when we watch a 3D movie or look into a stereoscopic viewer. While the basic perceptual phenomena of stereoscopic vision have been known for some time, it is mainly within the last 50 years that we have gained an understanding of how the nervous system delivers this sense of depth. This period of research began with the identification of neuronal signals for binocular depth in the primary visual cortex. Building on that finding, subsequent work has traced the signaling pathways for binocular stereoscopic depth forward into extrastriate cortex and further on into cortical areas concerning with sensorimotor integration. Within these pathways, neurons acquire sensitivity to more complex, higher order aspects of stereoscopic depth. Signals relating to the relative depth of visual features can be identified in the extrastriate cortex, which is a form of selectivity not found in the primary visual cortex. Over the same time period, knowledge of the organization of binocular vision in animals that inhabit a wide diversity of ecological niches has substantially increased. The implications of these findings for developmental and adult plasticity of the visual nervous system and onset of the clinical condition of amblyopia are explored in this article. Amblyopic vision is associated with a cluster of different visual and oculomotor symptoms, but the loss of high-quality stereoscopic depth performance is one of the consistent clinical features. Understanding where and how those losses occur in the visual brain is an important goal of current research, for both scientific and clinical reasons.