The magnetic field of the earth provides birds with navigational information, with birds having two different receptor systems, one for the direction, the other for the intensity of the geomagnetic field. The direction of the geomagnetic field is used as a compass, with the avian magnetic compass being an inclination compass not recording the polarity of the field. The respective directional information is perceived by light-dependent radical pair processes in the eyes, with cryptochrome, a photopigment with the chromophore flavin adenine dinucleotide as receptor molecule. It is transmitted by the optic nerve to the brain, where it is processed by parts of the visual system. The magnetic compass not only serves to orient avian flights but also acts as a reference system for route reversal, calibrating the astronomical compass systems, and in migratory birds, as reference for the innate information on the migratory direction. Magnetic intensity and inclination that show gradients from the poles to the magnetic equator are part of the mechanisms that allow birds to determine their position. Intensity is perceived by receptors based on magnetite, a permanently magnetic material. The effect of a brief, strong magnetic pulse and its duration indicates that superparamagnetic particles are involved. The respective information is transmitted by the ophthalmic branch of the trigeminal nerve to the trigeminal brainstem complex in the brain. Testing birds in magnetic fields of a distant site, i.e., magnetically simulating a displacement, documents that magnetic intensity and inclination are very most important components of the navigational “map” that enables birds to determine their position relative to the goal and thus derive the compass course leading to this goal. Furthermore, certain magnetic conditions act as signposts and elicit specific spontaneous responses.
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Article
Magnetoreception and Bird Navigation
Roswitha Wiltschko and Wolfgang Wiltschko
Article
Mammalian Visual System Organization
Farran Briggs
Many mammals, including humans, rely primarily on vision to sense the environment. While a large proportion of the brain is devoted to vision in highly visual animals, there are not enough neurons in the visual system to support a neuron-per-object look-up table. Instead, visual animals evolved ways to rapidly and dynamically encode an enormous diversity of visual information using minimal numbers of neurons (merely hundreds of millions of neurons and billions of connections!). In the mammalian visual system, a visual image is essentially broken down into simple elements that are reconstructed through a series of processing stages, most of which occur beneath consciousness. Importantly, visual information processing is not simply a serial progression along the hierarchy of visual brain structures (e.g., retina to visual thalamus to primary visual cortex to secondary visual cortex, etc.). Instead, connections within and between visual brain structures exist in all possible directions: feedforward, feedback, and lateral. Additionally, many mammalian visual systems are organized into parallel channels, presumably to enable efficient processing of information about different and important features in the visual environment (e.g., color, motion). The overall operations of the mammalian visual system are to: (1) combine unique groups of feature detectors in order to generate object representations and (2) integrate visual sensory information with cognitive and contextual information from the rest of the brain. Together, these operations enable individuals to perceive, plan, and act within their environment.
Article
Maternal Behavior From a Neuroendocrine Perspective
Danielle S. Stolzenberg, Kimberly L. Hernandez-D'Anna, Oliver J. Bosch, and Joseph S. Lonstein
For female mammals, caring for young until weaning or even longer is an extension of the reproductive burden that begins at insemination. Given the high price females potentially pay for failing to transmit genetic material to future generations, a multitude of interacting endocrine, neuroendocrine, and other neurochemical determinants are in place to ensure competent maternal caregiving by the time the offspring are born. Achieving this high maternal competency at parturition seems effortless but is quite a feat given that many nulliparous and parentally inexperienced female mammals are more prone to ignore, if not outright harm, conspecific neonates. There are important roles for ovarian steroids (e.g., estradiol and progesterone), adrenal steroids (e.g., glucocorticoids), and neuropeptide hormones (e.g., prolactin, oxytocin, arginine-vasopressin, and corticotropin-releasing factor) released during pregnancy, parturition, and postpartum in the onset and maintenance of caregiving behaviors in a broad range of commonly studied animals including rats, mice, rabbits, sheep, and primates. It is especially remarkable that the same collection of hormones influences caregiving similarly across these diverse animals, although to varying degrees. In addition to the well-known effects of hormones and neuropeptides on motherhood, more recent research indicates that experience-dependent epigenetic effects are also powerful modulators of the same neural substrates that can influence maternal responding.
Article
Mechanisms of Behavioral Changes After Spinal Cord Injury
Karim Fouad, Abel Torres-Espín, and Keith K. Fenrich
Spinal cord injury results in a wide range of behavioral changes including impaired motor and sensory function, autonomic dysfunction, spasticity, and depression. Currently, restoring lost motor function is the most actively studied and sought-after goal of spinal cord injury research. This research is rooted in the fact that although self-repair following spinal cord injury in adult mammals is very limited, there can be some recovery of motor function. This recovery is strongly dependent on the lesion size and location as well as on neural activity of denervated networks activated mainly through physical activity (i.e., rehabilitative training). Recovery of motor function is largely due to neuroplasticity, which includes adaptive changes in spared and injured neural circuitry. Neuroplasticity after spinal cord injury is extensive and includes mechanisms such as moderate axonal sprouting, the formation of new synaptic connections, network remapping, and changes to neuron cell properties. Neuroplasticity after spinal cord injury has been described at various physiological and anatomical levels of the central nervous system including the brain, brainstem, and spinal cord, both above and below injury sites. The growing number of mechanisms underlying postinjury plasticity indicate the vast complexity of injury-induced plasticity. This poses important opportunities to further enhance and harness plasticity in order to promote recovery. However, the diversity of neuroplasticity also creates challenges for research, which is frequently based on mechanistically driven approaches. The appreciation of the complexity of neuronal plasticity and the findings that recovery is based on a multitude and interlinked adaptations will be essential in developing meaningful new treatment avenues.
Article
The Medieval Cell Doctrine
Douglas J. Lanska
The medieval cell doctrine was a series of speculative psychological models derived from ancient Greco-Roman ideas in which cognitive faculties were assigned to “cells,” typically but not exclusively corresponding to the cerebral ventricles. During Late Antiquity and continuing during the Early Middle Ages, Christian philosophers reinterpreted Aristotle’s De Anima, along with later modifications by Herophilos and Galen, in a manner consistent with Christian doctrine. The resulting medieval cell doctrine was formulated by the fathers of the early Christian Church in the 4th and 5th centuries. Illustrations of the medieval cell doctrine were included in manuscripts since at least the 11th century. Printed images of the doctrine appeared in medical, philosophical, and religious works beginning with “graphic incunabula” at the end of the 15th century. Some of these early psychological models assigned various cognitive faculties to different nonoverlapping “cells” within the brain, while others specifically promoted or implied a linear sequence of events. By the 16th century, printed images of the doctrine were usually linear three-cell versions, with few exceptions having four or five cells. These psychological models were based on philosophical speculations rather than clinicopathologic evidence or experimentation. Despite increasingly realistic representations of the cerebral ventricles from the end of the 15th century until the middle of the 16th century, and direct challenges by Massa and Vesalius in the early 16th century and Willis in the 17th century, the doctrine saw its most elaborate formulations in the late 16th and early 17th centuries with illustrations by the Paracelsian physicians Bacci and Fludd. In addition, Descartes reinvigorated the ventricular localization of cerebral faculties in the 17th century beginning with his La Dioptrique (1637) and later with the Latin and French editions of his posthumously published Treatise of Man (1662-1667). Overthrow of the doctrine had to await the development of alternative models of brain function in the 17th and 18th centuries.
Article
Membrane-Initiated Estradiol Signaling in the Central Nervous System
Paul E. Micevych and Melinda A. Mittelman-Smith
In the last two decades of the 20th century, key findings in the field of estrogen signaling completely changed our understanding of hormones: first, steroidogenesis was demonstrated in the CNS; second, a vast majority of cells in the nervous system were shown to have estrogen receptors; third, a second nuclear estrogen receptor (ERß) was cloned; and finally, “nuclear” receptors were shown to be present and functional in the cell membrane. Shortly thereafter, even more membrane estrogen receptors were discovered. Steroids (estrogens, in particular) began to be considered as neurotransmitters and their receptors were tethered to G protein-coupled receptor signaling cascades. In some parts of the brain, levels of steroids appeared to be independent of those found in the circulation and yet, circulating steroids had profound actions on the brain physiology. In this review, we discuss the interaction of peripheral and central estrogen action in the context of female reproduction—one of the best-studied aspects of steroid action. In addition to reviewing the evidence for steroidogenesis in the hypothalamus, we review membrane-localized nuclear receptors coupling to G protein-signaling cascades and the downstream physiological consequences for reproduction. We will also introduce newer work that demonstrates cell signaling for a common splice variant of estrogen receptor-α (ERα), and membrane action of neuroprogesterone in regulating estrogen positive feedback.
Article
Mineralocorticoid Receptors and Glucocorticoid Receptors in HPA Stress Responses During Coping and Adaptation
Edo Ronald de Kloet and Marian Joëls
The glucocorticoid hormones cortisol and corticosterone coordinate circadian events and are master regulators of the stress response. These actions of the glucocorticoids are mediated by mineralocorticoid receptors (NR3C2, or MRs) and glucocorticoid receptors (NR3C1, or GRs). MRs bind the natural glucocorticoids cortisol and corticosterone with a 10-fold higher affinity than GRs. The glucocorticoids are inactivated only in the nucleus tractus solitarii (NTS), rendering the NTS-localized MRs aldosterone-selective and involved in regulation of salt appetite. Everywhere else in the brain MRs are glucocorticoid-preferring. MR and GR are transcription factors involved in gene regulation but recently were also found to mediate rapid non-genomic actions. Genomic MRs, with a predominant localization in limbic circuits, are important for the threshold and sensitivity of the stress response system. Non-genomic MRs promote appraisal processes, memory retrieval, and selection of coping style. Activation of GRs makes energy substrates available and dampens initial defense reactions. In the brain, GR activation enhances appetitive- and fear-motivated behavior and promotes memory storage of the selected coping style in preparation of the future. Thus, MRs and GRs complement each other in glucocorticoid control of the initiation and termination of the stress response, suggesting that the balance in MR- and GR-mediated actions is crucial for homeostasis and health.
Article
Models of Decision-Making Over Time
Paul Cisek and David Thura
Making a good decision often takes time, and in general, taking more time improves the chances of making the right choice. During the past several decades, the process of making decisions in time has been described through a class of models in which sensory evidence about choices is accumulated until the total evidence for one of the choices reaches some threshold, at which point commitment is made and movement initiated. Thus, if sensory evidence is weak (and noise in the signal increases the probability of an error), then it takes longer to reach that threshold than if sensory evidence is strong (thus helping filter out the noise). Crucially, the setting of the threshold can be increased to emphasize accuracy or lowered to emphasize speed. Such accumulation-to-bound models have been highly successful in explaining behavior in a very wide range of tasks, from perceptual discrimination to deliberative thinking, and in providing a mechanistic explanation for the observation that neural activity during decision-making tends to build up over time. However, like any model, they have limitations, and recent studies have motivated several important modifications to their basic assumptions. In particular, recent theoretical and experimental work suggests that the process of accumulation favors novel evidence, that the threshold decrease over time, and that the result yields improved decision-making in real, natural situations.
Article
Molecular Biology and Physiology of Circadian Clocks
Ruifeng Cao
Circadian rhythm is the approximately 24-hour rhythmicity that regulates physiology and behavior in a variety of organisms. The mammalian circadian system is organized in a hierarchical manner. Molecular circadian oscillations driven by genetic feedback loops are found in individual cells, whereas circadian rhythms in different systems of the body are orchestrated by the master clock in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. SCN receives photic input from retina and synchronizes endogenous rhythms with the external light/dark cycles. SCN regulates circadian rhythms in the peripheral oscillators via neural and humoral signals, which account for daily fluctuations of the physiological processes in these organs. Disruption of circadian rhythms can cause health problems and circadian dysfunction has been linked to many human diseases.
Article
Molecular Biology of Vertebrate Olfactory Receptors and Circuits
Richard P. Tucker and Qizhi Gong
Animals use their olfactory system for the procurement of food, the detection of danger, and the identification of potential mates. In vertebrates, the olfactory sensory neuron has a single apical dendrite that is exposed to the environment and a single basal axon that projects to the central nervous system (i.e., the olfactory bulb). The first odorant receptors to be discovered belong to an enormous gene family encoding G protein-coupled seven transmembrane domain proteins. Odorant binding to these classical odorant receptors initiates a GTP-dependent signaling cascade that uses cAMP as a second messenger. Subsequently, additional types of odorant receptors using different signaling pathways have been identified. While most olfactory sensory neurons are found in the olfactory sensory neuroepithelium, others are found in specialized olfactory subsystems. In rodents, the vomeronasal organ contains neurons that recognize pheromones, the septal organ recognizes odorant and mechanical stimuli, and the neurons of the Grüneberg ganglion are sensitive to cool temperatures and certain volatile alarm signals. Within the olfactory sensory neuroepithelium, each sensory neuron expresses a single odorant receptor gene out of the large gene family; the axons of sensory neurons expressing the same odorant receptor typically converge onto a pair of glomeruli at the periphery of the olfactory bulb. This results in the transformation of olfactory information into a spatially organized odortopic map in the olfactory bulb. The axons originating from the vomeronasal organ project to the accessory olfactory bulb, whereas the axons from neurons in the Grüneberg ganglion project to 10 specific glomeruli found in the caudal part of the olfactory bulb. Within a glomerulus, the axons originating from olfactory sensory neurons synapse on the dendrites of olfactory bulb neurons, including mitral and tufted cells. Mitral cells and tufted cells in turn project directly to higher brain centers (e.g., the piriform cortex and olfactory tubercle). The integration of olfactory information in the olfactory cortices and elsewhere in the central nervous system informs and directs animal behavior.
Article
Molecular Regulation of Energy Balance
D. Grahame Hardie and A. Mark Evans
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that monitors the levels of AMP and ADP relative to ATP. If increases in AMP:ATP and/or ADP:ATP ratios are detected (indicating a reduction in cellular energy status), AMPK is activated by the canonical mechanism involving both allosteric activation and enhanced net phosphorylation at Thr172 on the catalytic subunit. Once activated, AMPK phosphorylates dozens of downstream targets, thus switching on catabolic pathways that generate ATP and switching off anabolic pathways and other energy-consuming processes. AMPK can also be activated by non-canonical mechanisms, triggered either by glucose starvation by a mechanism independent of changes in adenine nucleotides, or by increases in intracellular
Ca
2
+
in response to hormones, mediated by the alternate upstream kinase CaMKK2.
AMPK is expressed in almost all eukaryotic cells, including neurons, as heterotrimeric complexes comprising a catalytic α subunit and regulatory β and γ subunits. The α subunits contain the kinase domain and regulatory regions that interact with the other two subunits. The β subunits contain a domain that, with the small lobe of the kinase domain on the α subunit, forms the “ADaM” site that binds synthetic drugs that are potent allosteric activators of AMPK, while the γ subunits contain the binding sites for the classical regulatory nucleotides, AMP, ADP, and ATP.
Although much undoubtedly remains to be discovered about the roles of AMPK in the nervous system, emerging evidence has confirmed the proposal that, in addition to its universal functions in regulating energy balance at the cellular level, AMPK also has cell- and circuit-specific roles at the whole-body level, particularly in energy homeostasis. These roles are mediated by phosphorylation of neural-specific targets such as ion channels, distinct from the targets by which AMPK regulates general, cell-autonomous energy balance. Examples of these cell- and circuit-specific functions discussed in this review include roles in the hypothalamus in balancing energy intake (feeding) and energy expenditure (thermogenesis), and its role in the brainstem, where it supports the hypoxic ventilatory response (breathing), increasing the supply of oxygen to the tissues during systemic hypoxia.
Article
Motion Processing in Primates
Tyler S. Manning and Kenneth H. Britten
The ability to see motion is critical to survival in a dynamic world. Decades of physiological research have established that motion perception is a distinct sub-modality of vision supported by a network of specialized structures in the nervous system. These structures are arranged hierarchically according to the spatial scale of the calculations they perform, with more local operations preceding those that are more global. The different operations serve distinct purposes, from the interception of small moving objects to the calculation of self-motion from image motion spanning the entire visual field. Each cortical area in the hierarchy has an independent representation of visual motion. These representations, together with computational accounts of their roles, provide clues to the functions of each area. Comparisons between neural activity in these areas and psychophysical performance can identify which representations are sufficient to support motion perception. Experimental manipulation of this activity can also define which areas are necessary for motion-dependent behaviors like self-motion guidance.
Article
Multisensory Integration and the Perception of Self-Motion
Kathleen E. Cullen
As we go about our everyday activities, our brain computes accurate estimates of both our motion relative to the world, and of our orientation relative to gravity. Essential to this computation is the information provided by the vestibular system; it detects the rotational velocity and linear acceleration of our heads relative to space, making a fundamental contribution to our perception of self-motion and spatial orientation. Additionally, in everyday life, our perception of self-motion depends on the integration of both vestibular and nonvestibular cues, including visual and proprioceptive information. Furthermore, the integration of motor-related information is also required for perceptual stability, so that the brain can distinguish whether the experienced sensory inflow was a result of active self-motion through the world or if instead self-motion that was externally generated. To date, understanding how the brain encodes and integrates sensory cues with motor signals for the perception of self-motion during natural behaviors remains a major goal in neuroscience. Recent experiments have (i) provided new insights into the neural code used to represent sensory information in vestibular pathways, (ii) established that vestibular pathways are inherently multimodal at the earliest stages of processing, and (iii) revealed that self-motion information processing is adjusted to meet the needs of specific tasks. Our current level of understanding of how the brain integrates sensory information and motor-related signals to encode self-motion and ensure perceptual stability during everyday activities is reviewed.
Article
The Natural Scene Network
Diane Beck and Dirk B. Walther
Interest in the neural representations of scenes centered first on the idea that the primate visual system evolved in the context of natural scene statistics, but with the advent of functional magnetic resonance imaging, interest turned to scenes as a category of visual representation distinct from that of objects, faces, or bodies. Research comparing such categories revealed a scene network comprised of the parahippocampal place area, the medial place area, and the occipital place area. The network has been linked to a variety of functions, including navigation, categorization, and contextual processing. Moreover, much is known about both the visual representations of scenes within the network as well as its role in and connections to the brain’s semantic system. To fully understand the scene network, however, more work is needed to both break it down into its constituent parts and integrate what is known into a coherent system or systems.
Article
Navigation Towards the Source Through Chemosensory Strategies and Mechanisms
Yaniv Cohen
Asymmetry of bilateral visual and auditory sensors has functional advantages for depth visual perception and localization of auditory signals, respectively. In order to detect the spatial distribution of an odor, bilateral olfactory organs may compare side differences of odor intensity and timing by using a simultaneous sampling mechanism; alternatively, they may use a sequential sampling mechanism to compare spatial and temporal input detected by one or several chemosensors. Extensive research on strategies and mechanisms necessary for odor source localization has been focused mainly on invertebrates. Several recent studies in mammals such as moles, rodents, and humans suggest that there is an evolutionary advantage in using stereo olfaction for successful navigation towards an odor source. Smelling in stereo or a three-dimensional olfactory space may significantly reduce the time to locate an odor source; this quality provides instantaneous information for both foraging and predator avoidance. However, since mammals are capable of finding odor sources and tracking odor trails with one sensor side blocked, they may use an intriguing temporal mechanism to compare odor concentration from sniff to sniff. A particular focus of this article is attributed to differences between insects and mammals regarding the use of unilateral versus bilateral chemosensors for odor source localization.
Article
Network Analyses and Nervous System Disorders
John D. Medaglia and Danielle S. Bassett
Network analyses in nervous system disorders involve constructing and analyzing anatomical and functional brain networks from neuroimaging data to describe and predict the clinical syndromes that result from neuropathology. A network view of neurological disease and clinical syndromes facilitates accurate quantitative characterizations and mathematical models of complex nervous system disorders with relatively simple tools drawn from the field of graph theory. Networks are predominantly constructed from in vivo data acquired using physiological and neuroimaging techniques at the macroscale of nervous system organization. Studies support the emerging view that neuropsychiatric and neurological disorders result from pathological processes that disrupt the brain’s economically wired small-world organization. The lens of network science offers theoretical insight into progressive neurodegeneration, neuropsychological dysfunction, and potential anatomical targets for interventions ranging from pharmacological agents to brain stimulation.
Article
The Neural Basis of Behavioral Sequences in Cortical and Subcortical Circuits
Katherine E. Conen and Theresa M. Desrochers
Sequences of actions and experiences are a central part of daily life in many species. Sequences consist of a set of ordered steps with a distinct beginning and end. They are defined by the serial order and relationships between items, though not necessarily by precise timing intervals. Sequences can be composed from a wide range of elements, including motor actions, perceptual experiences, memories, complex behaviors, or abstract goals. However, despite this variation, different types of sequences may share common features in neural coding. Examining the neural responses that support sequences is important not only for understanding the sequential behavior in daily life but also for investigating the array of diseases and disorders that impact sequential processes and the impact of therapeutics used to treat them. Research into the neural coding of sequences can be organized into the following broad categories: responses to ordinal position, coding of adjacency and inter-item relationships, boundary responses, and gestalt coding (representation of the sequence as a whole). These features of sequence coding have been linked to changes in firing rate patterns and neuronal oscillations across a range of cortical and subcortical brain areas and may be integrated in the lateral prefrontal cortex. Identification of these coding schemes has laid out an outline for understanding how sequences are represented at a neural level. Expanding from this work, future research faces fundamental questions about how these coding schemes are linked together to generate the complex range of sequential processes that influence cognition and behavior across animal species.
Article
Neural Control of Lower Urinary Tract Function
Jonathan M. Beckel and William C. de Groat
Functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain and lumbosacral spinal cord that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet via a combination of voluntary and reflex mechanisms. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. During urine storage, spinal sympathetic and somatic reflexes are active to maintain a quiescent bladder and a closed outlet. During micturition, these spinal storage reflexes are suppressed by input from the brain, while parasympathetic pathways in the brain are activated to produce a bladder contraction and relaxation of the urethra. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic pathway that consists of essential relay circuitry in the periaqueductal gray and pontine micturition center. These circuits in the rostral brain stem are, in turn, regulated by inputs from the forebrain that mediate voluntary control of micturition. Thus neural control of micturition is organized as a hierarchical system in which spinal storage reflexes and supraspinal voiding reflexes are regulated voluntarily by higher centers in the brain. In young children the voluntary mechanisms are undeveloped and voiding is purely reflex. Voluntary control emerges during maturation of the nervous system and depends on learned behavior. Diseases or injuries of the nervous system in adults cause re-emergence of involuntary micturition, leading to urinary incontinence.
Article
Neural Mechanisms for Odor-Guided Behavior
Giuliano Gaeta, Regina M. Sullivan, and Donald A. Wilson
Odor- or chemical-guided behavior is expressed in all species. Such behavioral responses to odors begin with transduction at olfactory receptors and, after initial processing in early stages of the olfactory system (e.g., vertebrate olfactory bulb, invertebrate antennal lobe), the information is rapidly (within one to two synapses) distributed to diverse brain regions controlling hedonics, metabolic balance, mating, and spatial navigation, among many other basic functions. Odors can not only drive or guide specific behavioral responses but can also modulate behavioral choices and affective state, in many cases in humans without conscious awareness. Many of the specific neural circuits underlying odor-guided behaviors have been partially described, though much remains unknown. Neural processes underlying odor-guided reward and aversion, kin recognition, feeding, orientation, and navigation across diverse species have been discussed, as well as odor modulation of human behavior and emotion.
Article
Neural Mechanisms of Tactile Texture Perception
Justin D. Lieber and Sliman J. Bensmaia
The ability to identify tactile objects depends in part on the perception of their surface microstructure and material properties. Texture perception can, on a first approximation, be described by a number of nameable perceptual axes, such as rough/smooth, hard/soft, sticky/slippery, and warm/cool, which exist within a complex perceptual space. The perception of texture relies on two different neural streams of information: Coarser features, measured in millimeters, are primarily encoded by spatial patterns of activity across one population of tactile nerve fibers, while finer features, down to the micron level, are encoded by finely timed temporal patterns within two other populations of afferents. These two streams of information ascend the somatosensory neuraxis and are eventually combined and further elaborated in the cortex to yield a high-dimensional representation that accounts for our exquisite and stable perception of texture.