Annelid worms are simultaneously an interesting and difficult model system for understanding the evolution of animal vision. On the one hand, a wide variety of photoreceptor cells and eye morphologies are exhibited within a single phylum; on the other, annelid phylogenetics has been substantially re-envisioned within the last decade, suggesting the possibility of considerable convergent evolution. This article reviews the comparative anatomy of annelid visual systems within the context of the specific behaviors exhibited by these animals. Each of the major classes of annelid visual systems is examined, including both simple photoreceptor cells (including leech body eyes) and photoreceptive cells with pigment (trochophore larval eyes, ocellar tubes, complex eyes); meanwhile, behaviors examined include differential mobility and feeding strategies, similarities (or differences) in larval versus adult visual behaviors within a species, visual signaling, and depth sensing. Based on our review, several major trends in the comparative morphology and ethology of annelid vision are highlighted: (1) eye complexity tends to increase with mobility and higher-order predatory behavior; (2) although they have simple sensors these can relay complex information through large numbers or multimodality; (3) polychaete larval and adult eye morphology can differ strongly in many mobile species, but not in many sedentary species; and (4) annelids exhibiting visual signaling possess even more complex visual systems than expected, suggesting the possibility that complex eyes can be simultaneously well adapted to multiple visual tasks.
Cynthia M. Harley and Mark K. Asplen
Cephalochordate Nervous System
Simona Candiani and Mario Pestarino
The central and peripheral nervous systems of amphioxus adults and larvae are characterized by morphofunctional features relevant to understanding the origins and evolutionary history of the vertebrate CNS. Classical neuroanatomical studies are mainly on adult amphioxus, but there has been a recent focus, both by TEM and molecular methods, on the larval CNS. The latter is small and remarkably simple, and new data on the localization of glutamatergic, GABAergic/glycinergic, cholinergic, dopaminergic, and serotonergic neurons within the larval CNS are now available. In consequence, it has been possible begin the process of identifying specific neuronal circuits, including those involved in controlling larval locomotion. This is especially useful for the insights it provides into the organization of comparable circuits in the midbrain and hindbrain of vertebrates. A much better understanding of basic chordate CNS organization will eventually be possible when further experimental data will emerge.
Developmental Neurobiology of Anxiety and Related Disorders
Emily M. Cohodes and Dylan G. Gee
The majority of anxiety disorders emerge during childhood and adolescence, a developmental period characterized by dynamic changes in frontolimbic circuitry. Frontolimbic circuitry plays a key role in fear learning and has been a focus of recent efforts to understand the neurobiological correlates of anxiety disorders across development. Although less is known about the neurobiological underpinnings of anxiety disorders in youth than in adults, studies of pediatric anxiety have revealed alterations in both the structure and function of frontolimbic circuitry. The amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus contribute to fear conditioning and extinction, and interactions between these regions have been implicated in anxiety during development. Specifically, children and adolescents with anxiety disorders show altered amygdala volumes and exhibit heightened amygdala activation in response to neutral and fearful stimuli, with the magnitude of signal change in amygdala reactivity corresponding to the severity of symptomatology. Abnormalities in the PFC and ACC and their connections with the amygdala may reflect weakened top-down control or compensatory efforts to regulate heightened amygdala reactivity associated with anxiety. Taken together, alterations in frontolimbic connectivity are likely to play a central role in the etiology and maintenance of anxiety disorders. Future studies should aim to translate the emerging understanding of the neurobiological bases of pediatric anxiety disorders to optimize clinical interventions for youth.
Enhancing the Regeneration of Neurons in the Central Nervous System
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.
Hemichordate Nervous System
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.
Investigating Learning and Memory in Humans
Evangelia G. Chrysikou, Elizabeth Espinal, and Alexandra E. Kelly
Memory refers to the set of cognitive systems and the neural structures that support them that allow humans to learn from experience, leverage this knowledge to understand and guide behavior in the present, and use past memories to think about and plan for the future. Neuroscience research on learning and memory has leveraged advances in behavioral methods, structural and functional brain imaging, noninvasive brain stimulation, and lesion studies to evaluate synergies and dissociations among small- and large-scale neural networks in support of memory performance. Overall, this work has converged to a conceptualization of new memories as representations of distributed patterns of neural activity across cortical and subcortical brain systems that provide neural grounding of sensorimotor and perceptual experiences, actions, thoughts, and emotions, and which can be reinstated as a result of internal or external cues. Most of this literature has supported dissociations among working and long-term memory, as well as between procedural, episodic, and semantic memories. On the other hand, progress in human neuroscience methodologies has revealed the interdependence of these memory systems in the context of complex cognitive tasks and suggests a dynamic and highly interactive neural architecture underlying human learning and memory. Future neuroscience research is anticipated to focus on understanding the neural mechanisms supporting this interactivity at the cellular and systems levels, as well as investigating the time course of their engagement.
Nicotinic Acetylcholine Receptors and Affective Responses
Kalynn Schulz, Marcia Chavez, and Arthur Castaneda
Nicotinic acetylcholine receptors (nAChRs) are present throughout the central nervous system and involved in a variety of physiological and behavioral functions. Nicotinic acetylcholine receptors are receptive to the presence of nicotine and acetylcholine and can be modulated through a variety of agonist and antagonist actions. These receptors are complex in their structure and function, and they are composed of multiple α and β subunits. Many affective disorders have etiological links with developmental exposure to the nAChR agonist nicotine. Given that abnormalities in nAChRs are associated with affective disorders such as depression and anxiety, pharmacological interventions targeting nAChRs may have significant therapeutic benefits.
Plasticity of Information Processing in the Auditory System
Andrew J. King
Information processing in the auditory system shows considerable adaptive plasticity across different timescales. This ranges from very rapid changes in neuronal response properties—on the order of hundreds of milliseconds when the statistics of sounds vary or seconds to minutes when their behavioral relevance is altered—to more gradual changes that are shaped by experience and learning. Many aspects of auditory processing and perception are sculpted by sensory experience during sensitive or critical periods of development. This developmental plasticity underpins the acquisition of language and musical skills, matches neural representations in the brain to the statistics of the acoustic environment, and enables the neural circuits underlying the ability to localize sound to be calibrated by the acoustic consequences of growth-related changes in the anatomy of the body. Although the length of these critical periods depends on the aspect of auditory processing under consideration, varies across species and brain level, and may be extended by experience and other factors, it is generally accepted that the potential for plasticity declines with age. Nevertheless, a substantial degree of plasticity is exhibited in adulthood. This is important for the acquisition of new perceptual skills; facilitates improvements in the detection or discrimination of fine differences in sound properties; and enables the brain to compensate for changes in inputs, including those resulting from hearing loss. In contrast to the plasticity that shapes the developing brain, perceptual learning normally requires the sound attribute in question to be behaviorally relevant and is driven by practice or training on specific tasks. Progress has recently been made in identifying the brain circuits involved and the role of neuromodulators in controlling plasticity, and an understanding of plasticity in the central auditory system is playing an increasingly important role in the treatment of hearing disorders.
Postnatal Neurogenesis in the Olfactory Bulb
Aleksandra Polosukhina and Pierre-Marie Lledo
This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Neuroscience. Please check back later for the full article. In adult mammals, the olfactory bulb and the hippocampus are the regions in the brain that undergo continuous neurogenesis (production and recruitment of newborn neurons). While the other regions of the brain still retain a certain degree of plasticity after birth, they no longer can integrate new neurons. In rodents, thousands of adult-born neurons integrate into the bulb each day, and this process has been found to contribute not only to sensory function, but also to olfactory memory. This was a surprising finding, since historically the adult-brain has been viewed as a static organ. Understanding the process of regeneration of mature neurons in the brain has great potential for therapeutic applications. Consequently, this process of adult-neurogenesis has received widespread attention from clinicians and scientists. Neuroblasts bound for the olfactory bulb are produced in the subventricular zone of the lateral ventricle. Once they reach the olfactory bulb, they mostly develop into inhibitory interneurons called granule cells. Just after one month, about half of the adult-born neurons are eliminated, and the other half fully integrate and function in the olfactory bulb. These cells not only process information from the sensory neurons in the bulb, but also receive massive innervation from various regions of the brain, including the olfactory cortex, locus coeruleus, the horizontal limb of diagonal band of Broca, and the dorsal raphe nucleus. The sensory (bottom-up) and cortical (top-down) activity has been found to play a vital role in the adult-born granule cell survival. Though the exact purpose of these newborn neurons has not been identified, some emerging functions include maintenance of olfactory bulb circuitry, modulating sensory information, modulating olfactory learning, and memory.
Regulating Systems in Neuroimmunology
William H. Walker II and A. Courtney DeVries
Neuroimmunology is the study of the interaction between the immune system and nervous system during development, homeostasis, and disease states. Descriptions of neuroinflammatory diseases dates back centuries. However, in depth scientific investigation in the field began in the late 19th century and continues into the 21st century. Contrary to prior dogma in the field of neuroimmunology, there is immense reciprocal crosstalk between the brain and the immune system throughout development, homeostasis, and disease states. Proper neuroimmune functioning is necessary for optimal health, as the neuroimmune system regulates vital processes including neuronal signaling, synapse pruning, and clearance of debris and pathogens within the central nervous system. Perturbations in optimal neuroimmune functioning can have detrimental consequences for the host and underlie a myriad of physical, cognitive, and behavioral abnormalities. As such, the field of neuroimmunology is still relatively young and dynamic and represents an area of active research and discovery.
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.
Using Neural Stem Cells to Enhance Repair and Recovery of Spinal Circuits After Injury
Itzhak Fischer and Shaoping Hou
Spinal cord injury is characterized by a complex set of events, which include the disruption of connectivity between the brain and the periphery with little or no spontaneous regeneration, resulting in motor, sensory and autonomic deficits. Transplantation of neural stem cells has the potential to provide the cellular components for repair of spinal cord injury (SCI), including oligodendrocytes, astrocytes, and neurons. The ability to generate graft-derived neurons can be used to restore connectivity by formation of functional relays. The critical requirements for building a relay are to achieve long-term survival of graft-derived neurons and promote axon growth into and out of the transplant. Recent studies have demonstrated that mixed populations of glial and neuronal progenitors provide a permissive microenvironment for survival and differentiation of early-stage neurons, but inclusion of growth factors with the transplant or cues for directional axon growth outside the transplant may also be needed. Other important considerations include the timing of the transplantation and the selection of a population of neurons that maximizes the effective transmission of signals. In some experiments, the essential neuronal relay formation has been developed in both sensory and motor systems related to locomotion, respiration, and autonomic functions. Despite impressive advances, the poor regenerative capacity of adult CNS combined with the inhibitory environment of the injury remain a challenge for achieving functional connectivity via supraspinal tracts, but it is possible that recruitment of local propriospinal neurons may facilitate the formation of relays. Furthermore, it is clear that the new connections will not be identical to the original innervation, and therefore there needs to be a mechanism for translating the resulting connectivity into useful function. A promising strategy is to mimic the process of neural development by exploiting the remarkable plasticity associated with activity and exercise to prune and strengthen synaptic connections. In the meantime, the sources of neural cells for transplantation are rapidly expanding beyond the use of fetal CNS tissue and now include pluripotent ES and iPS cells as well as cells obtained by direct reprogramming. These new options can provide considerable advantages with respect to preparation of cell stocks and the use of autologous grafting, but they present challenges of complex differentiation protocols and risks of tumor formation. It is important to note that although neural stem cell transplantation into the injured spinal cord is primarily designed to provide preclinical data for the potential treatment of patients with SCI, it can also be used to develop analogous protocols for repair of neuronal circuits in other regions of the CNS damaged by injury or neurodegeneration. The advantages of the spinal cord system include well-defined structures and a large array of quantitative functional tests. Therefore, studying the formation of a functional relay will address the fundamental aspects of neuronal cell replacement without the additional complexities associated with brain circuits.