Much progress has been made in unraveling the mechanisms that underlie the transition from acute to chronic pain. Traditional beliefs are being replaced by novel, more powerful concepts that consider the mutual interplay of neuronal and non-neuronal cells in the nervous system during the pathogenesis of chronic pain. The new focus is on the role of neuroinflammation for neuroplasticity in nociceptive pathways and for the generation, amplification, and mislocation of pain. The latest insights are reviewed here and provide a basis for understanding the interdependence of chronic pain and its comorbidities. The new concepts will guide the search for future therapies to prevent and reverse chronic pain.
Long-term changes in the properties and functions of nerve cells, including changes in synaptic strength, membrane excitability, and the effects of inhibitory neurotransmitters, can result from a wide variety of conditions. In the nociceptive system, painful stimuli, peripheral inflammation, nerve injuries, the use of or withdrawal from opioids—all can lead to enhanced pain sensitivity, to the generation of pain, and/or to the spread of pain to unaffected sites of the body. Non-neuronal cells, especially microglia and astrocytes, contribute to changes in nociceptive processing. Recent studies revealed not only that glial cells support neuroplasticity but also that their activation can trigger long-term changes in the nociceptive system.
Angel Ariel Caputi
American gymnotiformes and African mormyriformes have evolved an active sensory system using a self-generated electric field as a carrier of signals. Objects polarized by the discharge of a specialized electric organ project their images on the skin where electroreceptors tuned to the time course of the self-generated field transduce local signals carrying information about impedance, shape, size, and location of objects, as well as electrocommunication messages, and encode them as primary afferents trains of spikes. This system is articulated with other cutaneous systems (passive electroreception and mechanoception) as well as proprioception informing the shape of the fish’s body. Primary afferents project on the electrosensory lobe where electrosensory signals are compared with expectation signals resulting from the integration of recent past electrosensory, other sensory, and, in the case of mormyriformes, electro- and skeleton-motor corollary discharges. This ensemble of signals converges on the apical dendrites of the principal cells where a working memory of the recent past, and therefore predictable input, is continuously built up and updated as a pattern of synaptic weights. The efferent neurons of the electrosensory lobe also project to the torus and indirectly to other brainstem nuclei that implement automatic electro- and skeleton-motor behaviors. Finally, the torus projects via the preglomerular nucleus to the telencephalon where cognitive functions, including “electroperception” of shape-, size- and impedance-related features of objects, recognition of conspecifics, perception based decisions, learning, and abstraction, are organized.
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.
Yaniv Cohen, Emmanuelle Courtiol, Regina M. Sullivan, and Donald A. Wilson
Odorants, inhaled through the nose or exhaled from the mouth through the nose, bind to receptors on olfactory sensory neurons. Olfactory sensory neurons project in a highly stereotyped fashion into the forebrain to a structure called the olfactory bulb, where odorant-specific spatial patterns of neural activity are evoked. These patterns appear to reflect the molecular features of the inhaled stimulus. The olfactory bulb, in turn, projects to the olfactory cortex, which is composed of multiple sub-units including the anterior olfactory nucleus, the olfactory tubercle, the cortical nucleus of the amygdala, the anterior and posterior piriform cortex, and the lateral entorhinal cortex. Due to differences in olfactory bulb inputs, local circuitry and other factors, each of these cortical sub-regions appears to contribute to different aspects of the overall odor percept. For example, there appears to be some spatial organization of olfactory bulb inputs to the cortical nucleus of the amygdala, and this region may be involved in the expression of innate odor hedonic preferences. In contrast, the olfactory bulb projection to the piriform cortex is highly distributed and not spatially organized, allowing the piriform to function as a combinatorial, associative array, producing the emergence of experience-dependent odor-objects (e.g., strawberry) from the molecular features extracted in the periphery. Thus, the full perceptual experience of an odor requires involvement of a large, highly dynamic cortical network.
Sabine Kastner and Timothy J. Buschman
Natural scenes are cluttered and contain many objects that cannot all be processed simultaneously. Due to this limited processing capacity, neural mechanisms are needed to selectively enhance the information that is most relevant to one’s current behavior and to filter unwanted information. We refer to these mechanisms as “selective attention.” Attention has been studied extensively at the behavioral level in a variety of paradigms, most notably, Treisman’s visual search and Posner’s paradigm. These paradigms have also provided the basis for studies directed at understanding the neural mechanisms underlying attentional selection, both in the form of neuroimaging studies in humans and intracranial electrophysiology in non-human primates. The selection of behaviorally relevant information is mediated by a large-scale network that includes regions in all major lobes as well as subcortical structures. Attending to a visual stimulus modulates processing across the visual processing hierarchy with stronger effects in higher-order areas. Current research is aimed at characterizing the functions of the different network nodes as well as the dynamics of their functional connectivity.
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.
Jeffrey R. Holt and Gwenaëlle S.G. Géléoc
The organs of the vertebrate inner ear respond to a variety of mechanical stimuli: semicircular canals are sensitive to angular velocity, the saccule and utricle respond to linear acceleration (including gravity), and the cochlea is sensitive to airborne vibration, or sound. The ontogenically related lateral line organs, spaced along the sides of aquatic vertebrates, sense water movement. All these organs have a common receptor cell type, which is called the hair cell, for the bundle of enlarged microvilli protruding from its apical surface. In different organs, specialized accessory structures serve to collect, filter, and then deliver these physical stimuli to the hair bundles. The proximal stimulus for all hair cells is deflection of the mechanosensitive hair bundle. Hair cells convert mechanical information contained within the temporal pattern of hair bundle deflections into electrical signals, which they transmit to the brain for interpretation.
Understanding the principles by which sensory systems represent natural stimuli is one of the holy grails of neuroscience. In the auditory system, the study of the coding of natural sounds has a particular prominence. Indeed, the relationships between neural responses to simple stimuli (usually pure tone bursts)—often used to characterize auditory neurons—and complex sounds (in particular natural sounds) may be complex. Many different classes of natural sounds have been used to study the auditory system. Sound families that researchers have used to good effect in this endeavor include human speech, species-specific vocalizations, an “acoustic biotope” selected in one way or another, and sets of artificial sounds that mimic important features of natural sounds.
Peripheral and brainstem representations of natural sounds are relatively well understood. The properties of the peripheral auditory system play a dominant role, and further processing occurs mostly within the frequency channels determined by these properties. At the level of the inferior colliculus, the highest brainstem station, representational complexity increases substantially due to the convergence of multiple processing streams. Undoubtedly, the most explored part of the auditory system, in term of responses to natural sounds, is the primary auditory cortex. In spite of over 50 years of research, there is still no commonly accepted view of the nature of the population code for natural sounds in the auditory cortex. Neurons in the auditory cortex are believed by some to be primarily linear spectro-temporal filters, by others to respond to conjunctions of important sound features, or even to encode perceptual concepts such as “auditory objects.” Whatever the exact mechanism is, many studies consistently report a substantial increase in the variability of the response patterns of cortical neurons to natural sounds. The generation of such variation may be the main contribution of auditory cortex to the coding of natural sounds.
Age-related hearing loss affects over half of the elderly population, yet it remains poorly understood. Natural aging can cause the input to the brain from the cochlea to be progressively compromised in most individuals, but in many cases the cochlea has relatively normal sensitivity and yet people have an increasingly difficult time processing complex auditory stimuli. The two main deficits are in sound localization and temporal processing, which lead to poor speech perception. Animal models have shown that there are multiple changes in the brainstem, midbrain, and thalamic auditory areas as a function of age, giving rise to an alteration in the excitatory/inhibitory balance of these neurons. This alteration is manifest in the cerebral cortex as higher spontaneous and driven firing rates, as well as broader spatial and temporal tuning. These alterations in cortical responses could underlie the hearing and speech processing deficits that are common in the aged population.
Jose M. Alonso and Harvey A. Swadlow
The thalamocortical pathway is the main route of sensory information to the cerebral cortex. Vision, touch, hearing, taste, and balance all depend on the integrity of this pathway that connects the thalamic structures receiving sensory input with the cortical areas specialized in each sensory modality. Only the ancient sense of smell is independent of the thalamus, gaining access to cortex through more anterior routes. While the thalamocortical pathway targets different layers of the cerebral cortex, its main stream projects to the middle layers and has axon terminals that are dense, spatially restricted, and highly specific in their connections. The remarkable specificity of these thalamocortical connections allows for a precise reconstruction of the sensory dimensions that need to be most finely sampled, such as spatial acuity in vision and sound frequency in hearing. The thalamic axon terminals also segregate topographically according to their stimulus preferences, providing a simple principle to build cortical sensory maps: neighboring values in sensory space are represented by neighboring points within the cortex.
Thalamocortical processing is not static. It is continuously modulated by the brain stem and corticothalamic feedback based on the level of attention and alertness, and during sleep or general anesthesia. When alert, visual thalamic responses become stronger, more reliable, more sustained, more effective at sampling fast changes in the scene, and more linearly related to the stimulus. The high firing rates of the alert state make thalamocortical synapses chronically depressed and excitatory synaptic potentials less dependent on temporal history, improving even further the linear relation between stimulus and response. In turn, when alertness wanes, the thalamus reduces its firing rate, and starts generating spike bursts that drive large postsynaptic responses and keep the cortex responsive to sudden stimulus changes.