When one talks about hearing, some may first imagine the auricle (or external ear), which is the only visible part of the auditory system in humans and other mammals. Its shape and size vary among people, but it does not tell us much about a person’s abilities to hear (except perhaps their ability to localize sounds in space, where the shape of the auricle plays a certain role). Most of what is used for hearing is inside the head, particularly in the brain. The inner ear transforms mechanical vibrations into electrical signals; then the auditory nerve sends these signals into the brainstem, where intricate preprocessing occurs. Although auditory brainstem mechanisms are an important part of central auditory processing, it is the processing taking place in the cerebral cortex (with the thalamus as the mediator), which enables auditory perception and cognition. Human speech and the appreciation of music can hardly be imagined without a complex cortical network of specialized regions, each contributing different aspects of auditory cognitive abilities. During the evolution of these abilities in higher vertebrates, especially birds and mammals, the cortex played a crucial role, so a great deal of what is referred to as central auditory processing happens there. Whether it is the recognition of one’s mother’s voice, listening to Pavarotti singing or Yo-Yo Ma playing the cello, hearing or reading Shakespeare’s sonnets, it will evoke electrical vibrations in the auditory cortex, but it does not end there. Large parts of frontal and parietal cortex receive auditory signals originating in auditory cortex, forming processing streams for auditory object recognition and auditory-motor control, before being channeled into other parts of the brain for comprehension and enjoyment.
Josef P. Rauschecker
Chemoreception is the physiological capacity whereby organisms detect the varied external and internal chemical information required for survival and is the most primitive sensory process. Fish living in water have respiratory, gustatory, and olfactory chemosensory systems that detect water-soluble chemical cues. Respiratory chemoreception mainly in the gills detects changes in the levels of three respiratory gases: oxygen (O2), carbon dioxide (CO2), and ammonia (NH3). Gustatory chemoreception (gustation), which involves several taste receptor genes, is primarily involved in the tasting of foods. Olfactory chemoreception (olfaction), which involves between 15 and 150 olfactory receptor genes, is involved in a variety of important biological functions such as procuring foods, recognizing hazards (predators, contaminants, and toxic and alarm substances), discriminating species (individual, kin, and conspecific), controlling social behavior (dominance hierarchies, symbiotic behavior, territorial behavior, and schooling behavior), and reproductive and migratory behavior (mating, search for spawning site, imprinting, and homing). The olfactory functions are primarily controlled by hormones secreted from various endocrine glands that are the key mediators and integrators of external and internal information in organisms. Conversely, olfactory stimuli cause changes in hormone conditions. One good example is the amazing olfactory abilities of salmon. They can memorize information related to their natal stream odors during downstream migration in juveniles so that, after they travel thousands of kilometers in the ocean over many years during feeding migration, they are able to use their homing abilities to migrate precisely to their natal stream for reproduction in adults. Olfactory memory formation and retrieval of natal stream odors in salmon, which are primarily controlled by the brain–pituitary–thyroid hormones and brain–pituitary–gonad hormones, respectively, are essential to imprinting and homing migration. Salmon olfactory systems can discriminate seasonally and yearly stable compositions of dissolved amino acids in their natal streams produced by biofilms in the riverbed. Ocean and freshwater ecosystems may have been affected by climate change-related CO2-induced acidification that impairs olfactory-mediated neural and behavioral responses in fish.
Taylor Follansbee, Mirela Iodi Carstens, and E. Carstens
Pain is defined as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage,” while itch can be defined as “an unpleasant sensation that evokes the desire to scratch.” These sensations are normally elicited by noxious or pruritic stimuli that excite peripheral sensory neurons connected to spinal circuits and ascending pathways involved in sensory discrimination, emotional aversiveness, and respective motor responses. Specialized molecular receptors expressed by cutaneous nerve endings transduce stimuli into action potentials conducted by C- and Aδ-fiber nociceptors and pruriceptors into the outer lamina of the dorsal horn of the spinal cord. Here, neurons selectively activated by nociceptors, or by convergent input from nociceptors, pruriceptors, and often mechanoreceptors, transmit signals to ascending spinothalamic and spinoparabrachial pathways. The spinal circuitry for itch requires interneurons expressing gastrin-releasing peptide and its receptor, while spinal pain circuitry involves other excitatory neuropeptides; both itch and pain are transmitted by ascending pathways that express the receptor for substance P. Spinal itch- and pain-transmitting circuitry is segmentally modulated by inhibitory interneurons expressing dynorphin, GABA, and glycine, which mediate the antinociceptive and antipruritic effects of noxious counterstimulation. Spinal circuits are also under descending modulation from the brainstem rostral ventromedial medulla. Opioids like morphine inhibit spinal pain-transmitting circuits segmentally and via descending inhibitory pathways, while having the opposite effect on itch. The supraspinal targets of ascending pain and itch pathways exhibit extensive overlap and include the somatosensory thalamus, parabrachial nucleus, amygdala, periaqueductal gray, and somatosensory, anterior cingulate, insular, and supplementary motor cortical areas. Following tissue injury, enhanced pain is evoked near the injury (primary hyperalgesia) due to release of inflammatory mediators that sensitize nociceptors. Within a larger surrounding area of secondary hyperalgesia, innocuous mechanical stimuli elicit pain (allodynia) due to central sensitization of pain pathways. Pruriceptors can also become sensitized in pathophysiological conditions, such as dermatitis. Under chronic itch conditions, low-threshold tactile stimulation can elicit itch (alloknesis), presumably due to central sensitization of itch pathways, although this has not been extensively studied. There is considerable overlap in pain- and itch-signaling pathways and it remains unclear how these sensations are discriminated. Specificity theory states that itch and pain are separate sensations with their own distinct pathways (“labeled lines”). Selectivity theory is similar but incorporates the observation that pruriceptive neurons are also excited by algogenic stimuli that inhibit spinal itch transmission. In contrast, intensity theory states that itch is signaled by low firing rates, and pain by high firing rates, in a common sensory pathway. Finally, the spatial contrast theory proposes that itch is elicited by focal activation of a few nociceptors while activation of more nociceptors over a larger area elicits pain. There is evidence supporting each theory, and it remains to be determined how the nervous system distinguishes between pain and itch.
Mathew T. Summers, Malak El Quessny, and Marla B. Feller
Motion is a key feature of the sensory experience of visual animals. The mammalian retina has evolved a number of diverse motion sensors to detect and parse visual motion into behaviorally relevant neural signals. Extensive work has identified retinal outputs encoding directional and nondirectional motion, and the intermediate circuitry underlying this tuning. Detailed circuit mechanism investigation has established retinal direction selectivity in particular as a model system of neural computation.
Louisa J. Rinaldi
Synesthesia is a neurodevelopmental condition that causes 4.4% of the population to experience the world differently. For these individuals certain stimuli (e.g., letters of the alphabet) trigger a secondary experience (e.g., color perception). This process is automatic and remains consistent over time. Tests for measuring synesthesia have successfully built on this principle of synesthetic associations being consistent over time, and using this method a number of studies have investigated the heritability of the condition, cognitive differences that synesthetes have compared with non-synesthetes, and the neurological architecture of synesthete brains. These measures have largely focused on adult synesthetes for whom the condition is already fully developed. Since 2009 researchers have begun to also investigate childhood synesthesia, which has helped to advance our understanding of how this condition emerges. Drawing on both adult and child studies, we can better understand the neurological and cognitive implications of a lifetime of experiencing synesthetic associations.
Susan P. Travers and Alan C. Spector
Gustatory signals from the mouth travel to the rostral nucleus of the solitary tract (rNST) over the VIIth (anterior tongue and palate) and IXth (posterior tongue) cranial nerves and synapse in the central subdivision in an overlapping orotopic pattern. Oral somatosensory information likewise reaches rNST, preferentially terminating in the lateral subdivision. Two additional rNST subdivisions, the medial and ventral, receive only sparse primary afferent inputs. Ascending pathways arise primarily from the central subdivision; local reflex and intranuclear pathways originate from the other subdivisions. Thus, parallel processing is already evident at the first central nervous system (CNS) relay. Ascending rNST taste fibers connect to the pontine parabrachial nucleus (PBN), strongly terminating in the ventral lateral (VL) and medial subnuclei (M) of the waist region but also in the external lateral (EL) and medial (EM) subnuclei. PBN projections travel along two main routes. A “lemniscal” processing stream connects to the thalamic taste relay, the parvicellular division of the ventroposteromedial nucleus (VPMpc), which in turn projects to insular cortex. A second, “limbic” pathway synapses in the lateral hypothalamus (LH), central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (BNST), and substantia innominata (SI). The ventral tegmental area (VTA), a critical nucleus in the so-called reward circuit, also receives input from the gustatory PBN. Forebrain gustatory structures are interconnected and give rise to copious feedback pathways. Single-neuron recording and calcium imaging demonstrates that taste response profiles in both the peripheral nerves and CNS lemniscal structures are highly orderly. Arguably, a limited number of neuron “types” are defined by the qualitative class of compounds (sugars, sweeteners, amino acids, sodium salts, acids and non-sodium salts, “bitter”) that elicit the largest response in a cell. In the periphery and NST, some findings suggest these classes correspond to distinct molecular phenotypes and functions, but evidence for a cortical chemotopic organization is highly controversial. CNS neuron types are complicated by convergence and lability as a function of homeostatic, cognitive, and experiential variables. Moreover, gustatory responses are dynamic, providing additional coding potential in the temporal domain. Interestingly, taste responses in the limbic pathway are particularly plastic and code for hedonics more obviously than quality. Studies in decerebrate rats reveal that the brainstem is sufficient to maintain appropriate oromotor and somatic responses, referred to as taste reactivity, to nutritive (sugars) and harmful (quinine) stimuli. However, forebrain processing is necessary for taste reactivity to be modulated by learning, at least with respect to taste aversion conditioning. Functional studies of the rodent cortex tell a complex story. Lesion studies in rats emphasize a considerable degree of residual function in animals lacking large regions of insular cortex despite demonstrating shifts in detection thresholds for certain, but not all, stimuli representing different taste qualities. They also have an impact on conditioned taste aversion. Investigations in mice employing optogenetic and chemogenetic manipulations suggest that different regions of insular cortex are critical for discriminating certain qualities and that their connections to the amygdala underlie their hedonic impact. The continued use of sophisticated behavioral experiments coordinated with molecular methods for monitoring and manipulating activity in defined neural circuits should ultimately yield satisfying answers to long-standing debates about the fundamental operation of the gustatory system.
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.
Daniel W. Wesson, Sang Eun Ryu, and Hillary L. Cansler
The perception of odors exerts powerful influences on moods, decisions, and actions. Indeed, odor perception is a major driving force underlying some of the most important human behaviors. How is it that the simple inhalation of airborne molecules can exert such strong effects on complex aspects of human functions? Certainly, just like in the case of vision and audition, the perception of odors is dictated by the ability to transduce environmental information into an electrical “code” for the brain to use. However, the use of that information, including whether or not the information is used at all, is governed strongly by many emotional and cognitive factors, including learning and experiences, as well as states of arousal and attention. Understanding the manners whereby these factors regulate both the perception of odors and how an individual responds to those percepts are paramount for appreciating the orchestration of behavior.
Martha E. Bickford
Detailed studies of thalamic circuits have revealed many features that are shared across nuclei. For example, glutamatergic inputs to the thalamus can be placed into three categories based on the size of the synaptic terminals they form, their synaptic arrangements, and the postsynaptic responses they elicit. Remarkably, these three categories can be identified in most sensory nuclei of the dorsal thalamus. Likewise, in most sensory thalamic nuclei, circuits that release the neurotransmitter gamma aminobutyric acid (GABA) can be placed into two general categories based on their dendritic or axonal origins. Finally, similar cholinergic circuits have been identified across thalamic nuclei. The ultimate goal of examining the shared versus diverse features of thalamic circuits is to identify fundamental modules, mechanisms, and/or conceptual frameworks, in order to decipher thalamic function.
Alan C. Spector and Susan P. Travers
Everything a person swallows must pass a final chemical analysis by the sensory systems of the mouth; of these, the gustatory system is cardinal. Gustation can be heuristically divided into three basic domains of function: sensory-discriminative (quality and intensity), motivational/affective (promote or deter ingestion), and physiological (e.g., salivation and insulin release). The signals from the taste buds, transmitted to the brain through the sensory branches of cranial nerves VII (facial), IX (glossopharyngeal), and X (vagal), subserve these primary functions. Taste buds are collections of 50–100 cells that are distributed in various fields in the tongue, soft palate, and throat. There are three types of cells that have been identified in taste buds based on their morphological and cytochemical expression profiles. Type II cells express specialized G-protein-coupled receptors (GPCR or GPR) on their apical membranes, which protrude through a break in the oral epithelial lining called the taste pore, that are responsible for the sensing of sweeteners (via the taste type 1 receptor (T1R) 2 + T1R3), amino acids (via the T1R1+T1R3), and bitter ligands (via the taste type 2 receptors (T2Rs)). Type III cells are critical for the sensing of acids via the otopetrin-1 (Otop-1) ion channel. The sensing of sodium, in at least rodents, occurs through the epithelial sodium channel (ENaC), but the exact composition of this channel and the type of taste cell type in which the functional version resides remains unclear. It is controversial whether Type I cells, which have been characterized as glial-like, are involved in sodium transduction or play any taste signaling role. For the most part, receptors for different stimulus classes (e.g., sugars vs. bitter ligands) are not co-expressed, providing significant early functionally related segregation of signals. There remains a persistent search for yet to be identified receptors that may contribute to some functions associated with stimuli representing the so-called basic taste qualities—sweet, salty, sour, bitter, and umami—as well as unconventional stimuli such as fatty acids (in addition to cluster of differentiation-36 (CD-36), GPR40, and GPR120) and maltodextrins. The primary neurotransmitter in taste receptor cells is ATP, which is released through a voltage-gated heteromeric channel consisting of the calcium homeostasis modulator 1 and 3 (CALHM1/3) and binds with P2X2/X3 receptors on apposed afferent fibers. Serotonin released from Type III cells has been implicated as an additional neurotransmitter, binding with HT3a receptors, and possibly playing a role in acid taste (which is sour to humans). Taste bud cells undergo complete turnover about every two weeks. Although there remains much to be understood about the operations of the taste bud, perhaps the one very clear principle that emerges is that the organization of signals transmitted to the brain is not random and arbitrary to be decoded by complex algorithms in the circuits of the central gustatory system. Rather, the transmission of taste information from the periphery is highly ordered.