41-60 of 152 Results

Article

Romain Cartoni, Frank Bradke, and Zhigang He

Injured axons fail to regenerate in the adult mammalian central nervous system, representing a major barrier for effective neural repair. Both extrinsic inhibitory environments and neuron-intrinsic mechanisms contribute to such regeneration failure. In the past decade, there has been an explosion in our understanding of neuronal injury responses and regeneration regulations. As a result, several strategies have been developed to promote axon regeneration with the potential of restoring functions after injury. This article will highlight these new developments, with an emphasis on cellular and molecular mechanisms from a neuron-centric perspective, and discuss the challenges to be addressed toward developing effective functional restoration strategies.

Article

A first step in analyzing complex systems is a classification of component elements. This applies to retinal organization as well as to other circuit components in the visual system. There is great variety in the types of retinal ganglion cells and the targets of their axonal projections. Thus, a prerequisite to any deep understanding of the early visual system is developing a proper classification of its elements. How many distinct classes of retinal ganglion cells are there? Can the main classes be broken down into subclasses? What sort of functional correlates can be established for each class? Can homologous relationships between apparently similar classes between species be established? Can a common nomenclature based on homologous cell and circuit classes be developed?

Article

The neocortex is a part of the forebrain of mammals that is an innovation of mammal-like “reptilian” synapsid ancestors of early mammals. This neocortex emerged from a small region of dorsal cortex that was present in earlier ancestors and is still found in the forebrain of present-day reptiles. Instead of the thick structure of six layers of cells (five layers) and fibers (one layer) of neocortex of mammals, the dorsal cortex was characterized by a single layer of pyramidal neurons and a scattering of small, largely inhibitory neurons. In reptiles, the dorsal cortex is dominated by visual inputs, with outputs that relate to behavior and memory. The thicker neocortex of six layers in early mammals was already divided into a number of functionally specialized zones called cortical areas that were predominantly sensory in function, while relating to important aspects of motor behavior via subcortical projections. These early sensorimotor areas became modified in various ways as different branches of the mammalian radiation evolved, and neocortex often increased in size and the number of cortical areas, likely by the process of specializations within areas that subdivided areas. At least some areas, perhaps most, subdivided in another way by evolving two or more alternating types of small regions of different functional specializations, now referred to as cortical modules or columns. The specializations within and across cortical areas included those in the sizes of neurons and the extents of their processes, the dendrites and axons, and thus connections with other neurons. As a result, the neocortex of present-day mammals varies greatly within and across phylogenetically related groups (clades), while retaining basic features of organization from early ancestral mammals. In a number of present-day (extant) mammals, brains are relatively small and have little neocortex, with few areas and little structural differentiation, thus resembling early mammals. Other small mammals with little neocortex have specialized some part via selective enlargement and structural modifications to promote certain sensory abilities. Other mammals have a neocortex that is moderately to greatly expanded, with more cortical areas directly related to sensory processing and cognition and memory. The human brain is extreme in this way by having more neocortex in proportion to the rest of the brain, more cortical neurons, and likely more cortical areas.

Article

Tom Baden, Timm Schubert, Philipp Berens, and Thomas Euler

Visual processing begins in the retina—a thin, multilayered neuronal tissue lining the back of the vertebrate eye. The retina does not merely read out the constant stream of photons impinging on its dense array of photoreceptor cells. Instead it performs a first, extensive analysis of the visual scene, while constantly adapting its sensitivity range to the input statistics, such as the brightness or contrast distribution. The functional organization of the retina abides to several key organizational principles. These include overlapping and repeating instances of both divergence and convergence, constant and dynamic range-adjustments, and (perhaps most importantly) decomposition of image information into parallel channels. This is often referred to as “parallel processing.” To support this, the retina features a large diversity of neurons organized in functionally overlapping microcircuits that typically uniformly sample the retinal surface in a regular mosaic. Ultimately, each circuit drives spike trains in the retina’s output neurons, the retinal ganglion cells. Their axons form the optic nerve to convey multiple, distinctive, and often already heavily processed views of the world to higher visual centers in the brain. From an experimental point of view, the retina is a neuroscientist’s dream. While part of the central nervous system, the retina is largely self-contained, and depending on the species, it receives little feedback from downstream stages. This means that the tissue can be disconnected from the rest of the brain and studied in a dish for many hours without losing its functional integrity, all while retaining excellent experimental control over the exclusive natural network input: the visual stimulus. Once removed from the eyecup, the retina can be flattened, thus its neurons are easily accessed optically or using visually guided electrodes. Retinal tiling means that function studied at any one place can usually be considered representative for the entire tissue. At the same time, species-dependent specializations offer the opportunity to study circuits adapted to different visual tasks: for example, in case of our fovea, high-acuity vision. Taken together, today the retina is amongst the best understood complex neuronal tissues of the vertebrate brain.

Article

It is conceptually reasonable to explore how the evolution of behavior involves changes in neural circuitry. Progress in determining this evolutionary relationship has been limited in neuroscience because of difficulties in identifying individual neurons that contribute to the evolutionary development of behaviors across species. However, the results from the feeding systems of gastropod mollusks provide evidence for this concept of co-evolution because the evolution of different types of feeding behaviors in this diverse group of mollusks is mirrored by species-specific changes in neural circuitry. The evolution of feeding behaviors involves changes in the motor actions that allow diverse food items to be acquired and ingested. The evolution in neural control accompanies this variation in food and the associated changes in flexibility of feeding behaviors. This is present in components of the feeding network that are involved in decision making, rhythm generation, and behavioral switching but is absent in background mechanisms that are conserved across species, such as those controlling arousal state. These findings show how evolutionary changes, even at the single neuron level, closely reflect the details of behavioral evolution.

Article

Euopisthobranchia (Aplysia), Nudipleura (Tritonia, Hermissenda, Pleurobranchaea), and Panpulmonata (Lymnaea, Helix, Limax) gastropod mollusks exhibit a variety of reflex, rhythmic, and motivated behaviors that can be modified by elementary forms of learning and memory. The relative simplicity of their nervous systems and behavioral repertoires has allowed the uncovering of processes of neuronal and synaptic plasticity underlying non-associative learning, such as habituation, sensitization, and different forms of associative learning, such as classical and operant conditioning. Decades of work on these simpler and accessible animal systems have almost uniquely yielded an understanding into the mechanistic basis of learning and memory spanning behavior, neuronal circuitry, and molecules. Given the conservative nature of evolutionary processes, the mechanisms deciphered have also provided valuable insights into the neural basis of learning and memory in other metazoans, including higher vertebrates.

Article

Sensory systems exist to provide an organism with information about the state of the environment that can be used to guide future actions and decisions. Remarkably, two conceptually simple yet general theorems from information theory can be used to evaluate the performance of any sensory system. One theorem states that there is a minimal amount of energy that an organism has to spend in order to capture a given amount of information about the environment. The second theorem states that the maximum rate with which the organism can acquire resources from the environment, relative to its competitors, is limited by the information this organism collects about the environment, also relative to its competitors. These two theorems provide a scaffold for formulating and testing general principles of sensory coding but leave unanswered many important practical questions of implementation in neural circuits. These implementation questions have guided thinking in entire subfields of sensory neuroscience, and include: What features in the sensory environment should be measured? Given that we make decisions on a variety of time scales, how should one solve trade-offs between making simpler measurements to guide minimal decisions vs. more elaborate sensory systems that have to overcome multiple delays between sensation and action. Once we agree on the types of features that are important to represent, how should they be represented? How should resources be allocated between different stages of processing, and where is the impact of noise most damaging? Finally, one should consider trade-offs between implementing a fixed strategy vs. an adaptive scheme that readjusts resources based on current needs. Where adaptation is considered, under what conditions does it become optimal to switch strategies? Research over the past 60 years has provided answers to almost all of these questions but primarily in early sensory systems. Joining these answers into a comprehensive framework is a challenge that will help us understand who we are and how we can make better use of limited natural resources.

Article

Color is a central feature of human perceptual experience where it functions as a critical component in the detection, identification, evaluation, placement, and appreciation of objects in the visual world. Its role is significantly enhanced by the fact that humans evolved a dimension of color vision beyond that available to most other mammals. Many fellow primates followed a similar path and in recent years the basic mechanisms that support color vision—the opsin genes, photopigments, cone signals, and central processing—have been the subjects of hundreds of investigations. Because of the tight linkage between opsin gene structure and the spectral sensitivity of cone photopigments, it is possible to trace pathways along which color vision may have evolved in primates. In turn, such information allows the development of hypotheses about the nature of color vision and its utility in nonhuman primates. These hypotheses are being critically evaluated in field studies where primates solve visual problems in the presence of the full panoply of photic cues. The intent of this research is to determine which aspects of these cues are critically linked to color vision and how their presence facilitates, impedes, or fails to influence the solutions. These investigations are challenging undertakings and the emerging literature is replete with contradictory conclusions. But steady progress is being made and it appears that (a) some of the original ideas about there being a restricted number of tasks for which color vision might be optimally utilized by nonhuman primates (e. g., fruit harvest) were too simplistic and (b) depending on circumstances that can include both features of proximate visual stimuli (spectral cues, luminance cues, size cues, motion cues, overall light levels) and situational variables (social cues, developmental status, species-specific traits) the utilization of color vision by nonhuman primates is apt to be complex and varied.

Article

Kristina A. Kigerl and Phillip G. Popovich

Spinal cord injury (SCI) disrupts the autonomic nervous system (ANS) and impairs communication with organ systems throughout the body, resulting in chronic multi-organ pathology and dysfunction. This dysautonomia contributes to the pronounced immunosuppression and gastrointestinal dysfunction seen after SCI. All of these factors likely contribute to the development of gut dysbiosis after SCI—an imbalance in the composition of the gut microbiota that can impact the development and progression of numerous pathological conditions, including SCI. The gut microbiota are the community of microbes (bacteria, viruses, fungi) that live in the GI tract and are critical for nutrient absorption, digestion, and immune system development. These microbes also communicate with the CNS through modulation of the immune system, production of neuroactive metabolites and neurotransmitters, and activation of the vagus nerve. After SCI, gut dysbiosis develops and persists for more than one year from the time of injury. In experimental models of SCI, gut dysbiosis is correlated with changes in inflammation and functional recovery. Moreover, probiotic treatment can improve locomotor recovery and immune function in the gut-associated lymphoid tissue (GALT). Since different types of bacteria produce different metabolites with unique physiological and pathological effects throughout the body, it may be possible to predict the prevalence or severity of post-injury immune dysfunction and other related comorbidities (e.g., metabolic disease, fatigue, anxiety) using microbiome sequencing data. As research identifies microbial-derived small molecules and the genes responsible for their production, it is likely that it will become feasible to manipulate these molecules to affect human biology and disease.

Article

Norio Miyamoto and Hiroshi Wada

Hemichordates are marine invertebrates consisting of two distinct groups: the solitary enteropneusts and the colonial pterobranchs. Hemichordates are phylogenetically a sister group to echinoderm composing Ambulacraria. The adult morphology of hemichordates shares some features with chordates. For that reason, hemichordates have been considered key organisms to understand the evolution of deuterostomes and the origin of the chordate body plan. The nervous system of hemichordates is also important in the discussion of the origin of centralized nervous systems. However, unlike other deuterostomes, such as echinoderms and chordates, information on the nervous system of hemichordates is limited. Recent improvements in the accessibility of embryos, development of functional tools, and genomic resources from several model organisms have provided essential information on the nervous system organization and neurogenesis in hemichordates. The comparison of the nervous system between hemichordates and other bilaterians helps to elucidate the origin of the chordate central nervous system. Extant hemichordates are divided into two groups: enteropneusts and pterobranchs. The nervous system of adult enteropneusts consists of nerve cords and the basiepidermal nerve net. The two nerve cords run along the dorsal and ventral midlines. The dorsal nerve cord forms a tubular structure in the collar region. The two nerve cords are connected through the prebranchial nerve ring. The larval nervous system of enteropneusts develops along the ciliary band and there is a ganglion at the anterior end of the body called the apical ganglion. A pair of pigmented eyespots is situated at the lateral side of the apical ganglion. The adult nervous system of pterobranchs is basiepidermal and there are several condensations of plexuses. The most prominent one is the brain, located at the base of the tentaculated arms. From the brain, small fibers radiate and enter tentaculated arms to form a tentacle nerve in each. There is a basiepidermal nerve cord in the ventral midline of the trunk.

Article

The brain has limited processing capacities. Attention selection processes are continuously shaping humans’ world perception. Understanding the mechanisms underlying such covert cognitive processes requires the combination of psychophysical and electrophysiological investigation methods. This combination allows researchers to describe how individual neurons and neuronal populations encode attentional function. Direct access to neuronal information through innovative electrophysiological approaches, additionally, allows the tracking of covert attention in real time. These converging approaches capture a comprehensive view of attentional function.

Article

Peter Wenner and Pernille Bülow

Homeostatic plasticity refers to a collection of mechanisms that function to homeostatically maintain some feature of neural function. The field began with the view that homeostatic plasticity exists predominantly for the maintenance of spike rate. However, it has become clear that multiple features undergo some form of homeostatic control, including network activity, burst rate, or synaptic strength. There are several different forms of homeostatic plasticity, which are typically triggered following perturbations in activity levels. Homeostatic intrinsic plasticity (HIP) appears to compensate for the perturbation with changes in membrane excitability (voltage-gated conductances); synaptic scaling is thought to be a multiplicative increase or decrease of synaptic strengths throughout the cell following an activity perturbation; presynaptic homeostatic plasticity is a change in probability of release following a perturbation to postsynaptic receptor activity. Each form of homeostatic plasticity can be different in terms of the mechanisms that are engaged, the feature that is homeostatically regulated, the trigger that initiates the compensation, and the signaling cascades that mediate these processes. Homeostatic plasticity is often described in development, but can extend into maturity and has been described in vitro and in vivo.

Article

Eliot A. Brenowitz

Animals produce communication signals to attract mates and deter rivals during their breeding season. The coincidence in timing results from the modulation of signaling behavior and neural activity by sex steroid hormones associated with reproduction. Adrenal steroids can influence signaling for aggressive interactions outside the breeding season. Androgenic and estrogenic hormones act on brain circuits that regulate the motivation to produce and respond to signals, the motor production of signals, and the sensory perception of signals. Signal perception, in turn, can stimulate gonadal development.

Article

Jeremy C. Borniger and Luis de Lecea

The hypocretins (also known as orexins) are selectively expressed in a subset of lateral hypothalamic neurons. Since the reports of their discovery in 1998, they have been intensely investigated in relation to their role in sleep/wake transitions, feeding, reward, drug abuse, and motivated behavior. This research has cemented their role as a subcortical relay optimized to tune arousal in response to various salient stimuli. This article reviews their discovery, physiological modulation, circuitry, and integrative functionality contributing to vigilance state transitions and stability. Specific emphasis is placed on humoral and neural inputs regulating hcrt neural function and new evidence for an autoimmune basis of the sleep disorder narcolepsy. Future directions for this field involve dissection of the heterogeneity of this neural population using single-cell transcriptomics, optogenetic, and chemogenetics, as well as monitoring population and single cell activity. Computational models of the hypocretin network, using the “flip-flop” or “integrator neuron” frameworks, provide a fundamental understanding of how this neural population influences brain-wide activity and behavior.

Article

Brian P. Kenealy and Ei Terasawa

Female reproduction is an interplay between the hypothalamus, pituitary, and ovaries. While the gonadotropin releasing hormone (GnRH) neuron in the hypothalamus regulates gonadal function through the pituitary, GnRH neuronal activity is also profoundly influenced by ovarian steroid hormones. GnRH is released from GnRH neurons in a pulsatile manner after integration of a diverse array of internal and external milieus. Since the discovery of the mammalian GnRH molecule, over a dozen GnRH forms have been identified in the animal kingdom, and large numbers of publications in various lab animal and human studies suggest that GnRH neurons are regulated by multiple neuromodulators in the brain, such as kisspeptin, neurokinin B, β-dynorphin, neuropeptide Y, GnIH, GABA, glutamate, and glial factors. A recent emerging concept is that steroids synthesized locally in the hypothalamus, namely, neuroestradiol and neuroprogesterone, also contribute to the regulation of GnRH neuronal activity, and hence female reproduction. Together with modulation by various inputs and ovarian steroid feedback, GnRH neurons are responsible for puberty, cyclic ovulation, and menopause.

Article

Sex differences in the brain are established by the differential gonadal steroid hormonal milieu experienced by developing male and female fetuses and newborns. Androgen production by the testis starts in males prior to birth resulting in a brief developmental window during which the brain is exposed to high levels of steroid. Androgens and aromatized estrogens program the developing brain toward masculinized physiology and behavior that is then manifest in adulthood. In rodents, the perinatal programming of sex-specific adult mating behavior provides a model system for exploring the mechanistic origins of brain sex differences. Microglia are resident in the brain and provide innate immunity. Previously considered restricted to response to injury, these cells are now thought to be major contributors to the sculpting of developing neural circuits. This role extends to being an important component of the sexual differentiation process and has opened the door for exploration into myriad other aspects of neuroimmunity and inflammation as possible determinants of sex differences. In humans, males are at greater risk for more frequent and/or more severe neuropsychiatric and neurological disorders of development, many of which include prenatal inflammation as an additional risk factor. Emerging clinical and preclinical evidence suggests male brains experience a higher inflammatory tone early in development, and this may have its origins in the maternal immune system. Collectively, these disparate observations coalesce into a coherent picture in which brain development diverges in males versus females due to a combination of gonadal steroid action and neuroinflammation, and the latter increases the risk to males of developmental disorders.

Article

Natalie Hempel de Ibarra and Misha Vorobyev

Color plays an important role in insect life—many insects forage on colorful flowers and/or have colorful bodies. Accordingly, most insects have multiple spectral types of photoreceptors in their eyes, which gives them the capability to see colors. However, insects cannot perceive colors in the same way as human beings do because their eyes and brains differ substantially. An insect was the first nonhuman animal whose ability to discriminate colors has been demonstrated - in the beginning of the 20th century, von Frisch showed that the honeybee, Apis mellifera, can discriminate blue from any shade of gray. This method, called the gray-card experiment, is an accepted “gold standard” for the proof of color vision in animals. Insect species differ in the combinations of photoreceptors in their eyes, with peak sensitivities in ultraviolet (UV) and/or blue, green, and sometimes red parts of the spectrum. The number of photoreceptor spectral types can be as little as one or two, as in the grasshopper Phlaeoba and the beetle Tribolium, and as many as 10 and more in some species of butterflies and dragonflies. However, not all spectral receptor types are necessarily used for color vison. For example, the butterfly Papilio xuthus uses only four of its eight photoreceptors for color vision. Some insects have separate channels for processing chromatic and achromatic (lightness) information. In the honeybee, the achromatic channel has high spatial resolution and is mediated only by long-wavelength sensitive, or “green,” photoreceptors alone, whereas the spatial resolution of chromatic vision is low and mediated by all three spectral types of photoreceptors. Whether other insects have a similar separation of chromatic and achromatic vision remains uncertain. In contrast to vertebrates, insects do not use distinct sets of photoreceptors for nocturnal vision, and some nocturnal insects can see color at night. Insect photoreceptors are inherently polarization sensitive because of their microvillar organization. Therefore, some insects cannot discriminate changes in polarization of light from changes in its spectral composition. However, many insects sacrifice polarization sensitivity to retain reliable color vision. For example, in the honeybee, polarization sensitivity is eliminated by twisting the rhabdom in most parts of its compound eye except for the dorsal rim area that is specialized in polarization vision. Insects experience color constancy and color-contrast phenomena. Although in humans these aspects of vision are often attributed to cortical processing of color, simple models based on photoreceptor adaptation may explain color constancy and color induction in insects. Color discriminations can be evaluated using a simple model, which assumes that it is limited by photoreceptor noise. This model can help to predict discrimination of colors that are ecologically relevant, such as flower colors for pollinating insects. However, despite the fact that many insects forage on flowers, there is no evidence that insect pollinator vision coevolved with flower colors. The diverse color vision in butterflies appears to adaptively facilitate the recognition of their wing colors.

Article

Navigation is the ability of animals to move through their environment in a planned manner. Different from directed but reflex-driven movements, it involves the comparison of the animal’s current heading with its intended heading (i.e., the goal direction). When the two angles don’t match, a compensatory steering movement must be initiated. This basic scenario can be described as an elementary navigational decision. Many elementary decisions chained together in specific ways form a coherent navigational strategy. With respect to navigational goals, there are four main forms of navigation: explorative navigation (exploring the environment for food, mates, shelter, etc.); homing (returning to a nest); straight-line orientation (getting away from a central place in a straight line); and long-distance migration (seasonal long-range movements to a location such as an overwintering place). The homing behavior of ants and bees has been examined in the most detail. These insects use several strategies to return to their nest after foraging, including path integration, route following, and, potentially, even exploit internal maps. Independent of the strategy used, insects can use global sensory information (e.g., skylight cues), local cues (e.g., visual panorama), and idiothetic (i.e., internal, self-generated) cues to obtain information about their current and intended headings. How are these processes controlled by the insect brain? While many unanswered questions remain, much progress has been made in recent years in understanding the neural basis of insect navigation. Neural pathways encoding polarized light information (a global navigational cue) target a brain region called the central complex, which is also involved in movement control and steering. Being thus placed at the interface of sensory information processing and motor control, this region has received much attention recently and emerged as the navigational “heart” of the insect brain. It houses an ordered array of head-direction cells that use a wide range of sensory information to encode the current heading of the animal. At the same time, it receives information about the movement speed of the animal and thus is suited to compute the home vector for path integration. With the help of neurons following highly stereotypical projection patterns, the central complex theoretically can perform the comparison of current and intended heading that underlies most navigation processes. Examining the detailed neural circuits responsible for head-direction coding, intended heading representation, and steering initiation in this brain area will likely lead to a solid understanding of the neural basis of insect navigation in the years to come.

Article

During the evolution of animals, survival and reproduction depended upon mechanisms that maintained internal homeostasis in the face of environmental change. These environmental changes included fluctuations in ambient temperature, food availability, humidity, day length, and population density. Most, if not all, of these variables have effects on the availability of energy, and most vertebrate species have mechanisms that sense energy availability and adjust behavioral priorities accordingly. For example, when the availability of food and potential mating partners is stable and abundant, brain mechanisms often inhibit ingestive behavior, increase energy expenditure, and give priority to courtship and mating. In response to severe energy shortages, brain mechanisms are likely to stimulate foraging, food hoarding, and overeating. These same deficits often delay reproductive development or inhibit adult reproductive behavior. Such adaptations involve the integration of sensory signals with peripheral hormone signals and central effectors, and they are key to understanding health and disease, particularly obesity, eating disorders, and diabetes. The link between energy balance and reproduction recurs repeatedly, whether in the context of the sensory-somatic system, the autonomic nervous system, or the neuroendocrine cascades. Peripheral signals that are detected by receptors on vagal and splanchnic nerves are relayed to the caudal hindbrain. This brain area contains the effectors for peripheral hormone secretion and for chewing and swallowing, and this same brain area contains receptors for humoral and metabolic signals from peripheral circulation. The caudal hindbrain is therefore a strong candidate for integration of multiple signals that control the initiation of meals, meal size, energy storage, and energy expenditure, including the energy expended on reproduction. There are some differences between the reproductive and ingestive mechanisms, but there are also many striking similarities. There are still gaps in our knowledge about the nature and location of metabolic receptors and the pathways to their effectors. Some of the most promising research is designed to shed light on how hormonal signals might be enhanced or modulated by the peripheral energetic condition (e.g., the level of oxidizable metabolic fuels).

Article

Nathaniel J. Himmel, Atit A. Patel, and Daniel N. Cox

Nociception is a protective mechanism that mediates behavioral responses to a range of potentially damaging stimuli, including noxious temperature, chemicals, and mechanical stimulation. Nociceptive mechanisms are found throughout metazoans. Noxious stimuli are transduced by specialized, high-threshold peripheral nociceptors, which fire action potentials to elicit adaptive behavioral responses. Nociception is essential for survival and provides a mechanism for sensory perception of noxious stimuli, which alerts the organism to potential environmental dangers. When coupled with pain sensation and complex behavioral responses, this mechanism protects the organism from incipient damage. Moreover, acute and chronic pain may manifest as altered nociception in neuropathic pain states. Elucidating the neural bases of nociception is therefore important for identifying and implementing novel strategies for the treatment of neuropathic pain, as well as uncovering the mechanistic bases by which the nervous system integrates information to produce specific behaviors in response to a range of noxious stimuli. Invertebrate organisms, such as Drosophila melanogaster and Caenorhabditis elegans, have emerged as powerful, genetically tractable platforms for exploring these questions. Here, we concisely review the current state of knowledge regarding the cells, molecules, neural circuits, and behaviors associated with invertebrate nociception in the fruit fly and nematode worm.