Decoding the organization of spinal circuits that control locomotion.

Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait.

Structural mapping with fiber tractography of the human cuneate fasciculus at microscopic resolution in cervical region.

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.

Laterality of cerebellar afferent and efferent pathways in a healthy right-handed population: A diffusion tensor imaging study.

The cerebellum communicates with the cerebral cortex through the cortico-ponto-cerebellar tract (CPCT, cerebellar afferent) and the dentato-rubro-thalamo-cortical tract (DRTCT, cerebellar efferent). This study explored the laterality of CPCT and DRTCT in a right-handed population. Forty healthy right-handed subjects (18 males and 22 females with age range of 26-79 years old) who underwent diffusion tensor imaging (DTI) were retrospectively enrolled. Bilateral CPCT, DRTCT, and the corticospinal tract (CST) were reconstructed using probabilistic diffusion tensor tractography (DTT). Tract volume (TV) and fractional anisotropy (FA) were compared between dominant and non-dominant tracts. Subjects were divided into age groups (20-40, 41-60, and 61-80 years), and the DTI-derived parameters of the groups were compared to determine age-related differences. TV and FA of non-dominant CPCT were higher than those of dominant CPCT, and the dominant CST was higher than the non-dominant CST. The TV and FA of DRTCT showed no side-to-side difference. The 61-80 years age group had the highest TV of the dominant and non-dominant DRTCT among the three groups and the highest FA of the non-dominant CPCT and DRTCT. The results revealed the structural characteristics of CPCT and DRTCT using probabilistic DTT. Normal asymmetric patterns and age-related changes in cerebellar white matter tracts may be important to researchers investigating cerebro-cerebellar structural connectivity.

Neuronal Regression of Internal Leg Vibroreceptor Organs in a Cave-Dwelling Insect (Orthoptera: Rhaphidophoridae: Dolichopoda araneiformis).

Animals' adaptations to cave habitats generally include elaboration of extraoptic senses, and in insects the receptor structures located on the legs are supposed to become more prominent in response to constant darkness. The receptors for detecting substrate vibrations are often highly sensitive scolopidial sensilla localized within the legs or the body. For troglobitic insects the evolutionary changes in vibroreceptor organs have not been studied. Since rock is an extremely unfavorable medium for vibration transmission, selection on vibration receptors may be weakened in caves, and these sensory organs may undergo regressive evolution. We investigated the anatomy of the most elaborate internal vibration detection system in orthopteroid insects, the scolopidial subgenual organ complex in the cave cricket Dolichopoda araneiformis (Orthoptera: Ensifera: Rhaphidophoridae). This is a suitable model species which shows high levels of adaptation to cave life in terms of both phenotypic and life cycle characteristics. We compared our data with data on the anatomy and physiology of the subgenual organ complex from the related troglophilic species Troglophilus neglectus. In D. araneiformis, the subgenual organ complex contains three scolopidial organs: the subgenual organ, the intermediate organ, and the accessory organ. The presence of individual organs and their innervation pattern are identical to those found in T. neglectus, while the subgenual organ and the accessory organ of D. araneiformis contain about 50% fewer scolopidial sensilla than in T. neglectus. This suggests neuronal regression of these organs in D. araneiformis, which may reflect a relaxed selection pressure for vibration detection in caves. At the same time, a high level of overall neuroanatomical conservation of the intermediate organ in this species suggests persistence of the selection pressure maintaining this particular organ. While regressive evolution of chordotonal organs has been documented for insect auditory organs, this study shows for the first time that internal vibroreceptors can also be affected.

Functional organization of human subgenual cortical areas: Relationship between architectonical segregation and connectional heterogeneity.

Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region.

Coding complexity in the human motor circuit.

Cortical oscillatory dynamics are known to be critical for human movement, although their functional significance remains unclear. In particular, there is a strong beta (15-30 Hz) desynchronization that begins before movement onset and continues during movement, before rebounding after movement termination. Several studies have connected this response to motor planning and/or movement selection operations, but to date such studies have examined only the early aspects of the response (i.e., before movement) and a limited number of parameters. In this study, we used magnetoencephalography (MEG) and a novel motor sequence paradigm to probe how motor plan complexity modulates peri-movement beta oscillations, and connectivity within activated circuits. We also examined the dynamics by imaging beta activity before and during movement execution and extracting virtual sensors from key regions. We found stronger beta desynchronization during complex relative to simple sequences in the right parietal and left dorsolateral prefrontal cortex (DLPFC) during movement execution. There was also an increase in functional connectivity between the left DLPFC and right parietal shortly after movement onset during complex but not simple sequences, which produced a significant conditional effect (i.e., complex > simple) that was not attributable to differences in response amplitude. This study is the first to demonstrate that complexity modulates the dynamics of the peri-movement beta ERD, which provides crucial new data on the functional role of this well-known oscillatory motor response. These data further suggest that execution of complex motor behavior may recruit key regions of the fronto-parietal network, in addition to traditional sensorimotor regions.

The visceromotor and somatic afferent nerves of the penis.

INTRODUCTION: Innervation of the penis supports erectile and sensory functions. AIM: This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. METHODS: Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). MAIN OUTCOME MEASURES: The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. RESULTS: Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. CONCLUSIONS: There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment.

Physiology--how the body detects pain stimuli.

Pain is the body's way of telling us something is wrong. It has a sensory and emotional component. This three-part series focuses on acute pain, describing the physiology of a normal and well-behaved pain pathway and how this relates to commonly used pain-management strategies. This first article introduces the pain system and how the body detects a threatening (noxious) stimulus. Part two describes how that pain message is transmitted to the spinal cord and the brain, and the response of the brain to the stimulus. The third article discusses the assessment of pain.

Modality-based organization of ascending somatosensory axons in the direct dorsal column pathway.

The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the "somatotopic map" model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial-lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough "somatotopic map" was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway.

Thalamostriatal projections from the medial posterior and parafascicular nuclei have distinct topographic and physiologic properties.

The dorsolateral striatum (DLS) is critical for executing sensorimotor behaviors that depend on stimulus-response (S-R) associations. In rats, the DLS receives it densest inputs from primary somatosensory (SI) cortex, but it also receives substantial input from the thalamus. Much of rat DLS is devoted to processing whisker-related information, and thalamic projections to these whisker-responsive DLS regions originate from the parafascicular (Pf) and medial posterior (POm) nuclei. To determine which thalamic nucleus is better suited for mediating S-R associations in the DLS, we compared their input-output connections and neuronal responses to repetitive whisker stimulation. Tracing experiments demonstrate that POm projects specifically to the DLS, but the Pf innervates both dorsolateral and dorsomedial parts of the striatum. The Pf nucleus is innervated by whisker-sensitive sites in the superior colliculus, and these sites also send dense projections to the zona incerta, a thalamic region that sends inhibitory projections to the POm. These data suggest that projections from POm to the DLS are suppressed by incertal inputs when the superior colliculus is activated by unexpected sensory stimuli. Simultaneous recordings with two electrodes indicate that POm neurons are more responsive and habituate significantly less than Pf neurons during repetitive whisker stimulation. Response latencies are also shorter in POm than in Pf, which is consistent with the fact that Pf receives its whisker information via synaptic relays in the superior colliculus. These findings indicate that, compared with the Pf nucleus, POm transmits somatosensory information to the DLS with a higher degree of sensory fidelity.

The vomeronasal cortex - afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice.

Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that the posteromedial cortical nucleus of the amygdala is strongly interconnected not only with the rest of the vomeronasal system (AOB and its target structures in the amygdala), but also with the olfactory system (piriform cortex, olfactory-recipient nuclei of the amygdala and entorhinal cortex). Therefore, the posteromedial cortical nucleus of the amygdala probably integrates olfactory and vomeronasal information. In addition, the posteromedial cortical nucleus of the amygdala shows moderate interconnections with the associative (basomedial) amygdala and with the ventral hippocampus, which may be involved in emotional and spatial learning (respectively) induced by chemical signals. Finally, the posteromedial cortical nucleus of the amygdala gives rise to zinc-enriched projections to the ventrolateral septum and the ventromedial striatum (including the medial islands of Calleja). This pattern of intracortical connections (with the olfactory cortex and hippocampus, mainly) and cortico-striatal excitatory projections (with the olfactory tubercle and septum) is consistent with its proposed nature as the primary vomeronasal cortex.

Contrasting patterns of cortical input to architectural subdivisions of the area 8 complex: a retrograde tracing study in marmoset monkeys.

Contemporary studies recognize 3 distinct cytoarchitectural and functional areas within the Brodmann area 8 complex, in the caudal prefrontal cortex: 8b, 8aD, and 8aV. Here, we report on the quantitative characteristics of the cortical projections to these areas, using injections of fluorescent tracers in marmoset monkeys. Area 8b was distinct from both 8aD and 8aV due to its connections with medial prefrontal, anterior cingulate, superior temporal polysensory, and ventral midline/retrosplenial areas. In contrast, areas 8aD and 8aV received the bulk of the projections from posterior parietal cortex and dorsal midline areas. In the frontal lobe, area 8aV received projections primarily from ventrolateral areas, while both 8aD and 8b received dense inputs from areas on the dorsolateral surface. Whereas area 8aD received the most significant auditory projections, these were relatively sparse, in comparison with those previously reported in macaques. Finally, area 8aV was distinct from both 8aD and 8b by virtue of its widespread input from the extrastriate visual areas. These results are compatible with a homologous organization of the prefrontal cortex in New and Old World monkeys, and suggest significant parallels between the present pathways, revealed by tract-tracing, and networks revealed by functional connectivity analysis in Old World monkeys and humans.

Stimulation of trigeminal afferents improves motor recovery after facial nerve injury: functional, electrophysiological and morphological proofs.

Recovery of mimic function after facial nerve transection is poor: the successful regrowth of axotomized motoneurons to their targets is compromised by (1) poor axonal navigation and excessive collateral branching, (2) abnormal exchange of nerve impulses between adjacent regrowing axons, and (3) insufficient synaptic input to facial motoneurons. As a result, axotomized motoneurons get hyperexcitable and unable to discharge. Since improvement of growth cone navigation and reduction of the ephaptic cross talk between axons turn out be very difficult, we concentrated our efforts on the third detrimental component and proposed that an intensification of the trigeminal input to axotomized electrophysiologically silent facial motoneurons might improve specificity of reinnervation. To test our hypothesis we compared behavioral, electrophysiological, and morphological parameters after single reconstructive surgery on the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery but combined with direct or indirect stimulation of the ipsilateral infraorbital (ION) nerve. We found that in all cases, trigeminal stimulation was beneficial for the outcome by improving the quality of target reinnervation and recovery of vibrissa! motor performance.

Independent evolution of visual and electrosensory specializations in different lineages of mormyrid electric fishes.

African mormyrid fishes are by far the most diverse group of osteoglossomorph (bony tongue) fishes. Mormyrids communicate using pulses of electricity, and they process electric communication signals in the midbrain exterolateral nucleus (EL). In its ancestral form, the EL is relatively small and homogenous. In two different lineages, however, the EL expanded in size and increased in cytological complexity. This evolutionary change established the perceptual ability to distinguish variation in electric pulse waveform, which plays an important role in species recognition and mate choice. However, the sensory basis of social behavior in species with a small, homogenous EL remains unknown. Using published species descriptions, we found that species in one of these lineages have relatively large eyes. Using sectioned brains, we measured the volume of a major visual region, the optic tectum (OT), and found that this same lineage also has an enlarged OT. We also found that eye size and OT size are highly correlated across species. Phylogenetic analysis suggests that a reduced visual system evolved with the origins of an active electrosense, and that this one particular lineage secondarily evolved an enlarged visual system. Behavioral tests revealed that this enlargement of the visual system established increased visual acuity. Thus, our findings demonstrate that different lineages of mormyrids have evolved visual or electrosensory specializations, but that no lineages have specialized in both. This sensory divergence likely reflects fundamentally different ecologies and suggests that vision may play an especially important role in the social behavior of mormyrids that cannot detect variation in electric signal waveform. Our findings provide an example of evolutionary change in multiple sensory systems among closely related species that lays a foundation for relating ecological adaptation to evolutionary change in multisensory perception and social behavior.

Cortical connections of area V6Av in the macaque: a visual-input node to the eye/hand coordination system.

The goal of the present study was to elucidate the corticocortical afferent connections of area V6Av, the ventral subregion of area V6A, using retrograde neuronal tracers combined with physiological and cytoarchitectonic analyses in the macaque monkey. The results revealed that V6Av receives many of its afferents from extrastriate area V6, and from regions of areas V2, V3, and V4 subserving peripheral vision. Additional extrastriate visual projections originate in dorsal stream areas MT and MST. Area V6Av does not receive projections directly from V1; such connections were only observed when the injection sites crossed into area V6. The strongest parietal lobe afferents originate in fields V6Ad, PGm, MIP (medial intraparaietal), and PG, with frontal lobe afferents originating from the frontal eye field, caudal area 46, and the rostral subdivision of the dorsal premotor area (F7). A comparison of their respective connections supports the view that V6Av is functionally distinct from adjacent areas (V6 and V6Ad). The strong afferents from V6 and other extrastriate areas are consistent with physiological data that suggest that V6Av is primarily a visual area, supporting the notion that V6Av is part of a dorsomedial cortical network performing fast form and motion analyses needed for the visual guidance of action.

Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.

Cortical input to the frontal pole of the marmoset monkey.

We used fluorescent tracers to map the pattern of cortical afferents to frontal area 10 in marmosets. Dense projections originated in several subdivisions of orbitofrontal cortex, in the medial frontal cortex (particularly areas 14 and 32), and in the dorsolateral frontal cortex (particularly areas 8Ad and 9). Major projections also stemmed, in variable proportions depending on location of the injection site, from both the inferior and superior temporal sensory association areas, suggesting a degree of audiovisual convergence. Other temporal projections included the superior temporal polysensory cortex, temporal pole, and parabelt auditory cortex. Medial area 10 received additional projections from retrosplenial, rostral calcarine, and parahippocampal areas, while lateral area 10 received small projections from the ventral somatosensory and premotor areas. There were no afferents from posterior parietal or occipital areas. Most frontal connections were balanced in terms of laminar origin, giving few indications of an anatomical hierarchy. The pattern of frontopolar afferents suggests an interface between high-order representations of the sensory world and internally generated states, including working memory, which may subserve ongoing evaluation of the consequences of decisions as well as other cognitive functions. The results also suggest the existence of functional differences between subregions of area 10.

Differential patterns of inputs create functional zones in central nucleus of inferior colliculus.

Distinct pathways carry monaural and binaural information from the lower auditory brainstem to the central nucleus of the inferior colliculus (ICC). Previous anatomical and physiological studies suggest that differential ascending inputs to regions of the ICC create functionally distinct zones. Here, we provide direct evidence of this relationship by combining recordings of single unit responses to sound in the ICC with focal, iontophoretic injections of the retrograde tracer Fluoro-Gold at the physiologically characterized sites. Three main patterns of anatomical inputs were observed. One pattern was identified by inputs from the cochlear nucleus and ventral nucleus of the lateral lemniscus in isolation, and these injection sites were correlated with monaural responses. The second pattern had inputs only from the ipsilateral medial and lateral superior olive, and these sites were correlated with interaural time difference (ITD)-sensitive responses to low frequency (<500 Hz). A third pattern had inputs from a variety of olivary and lemniscal sources, notably the contralateral lateral superior olive and dorsal nucleus of the lateral lemniscus. These were correlated with high-frequency ITD sensitivity to complex acoustic stimuli. These data support the notion of anatomical regions formed by specific patterns of anatomical inputs to the ICC. Such synaptic domains may represent functional zones in ICC.

Prefrontal beta2 subunit-containing and alpha7 nicotinic acetylcholine receptors differentially control glutamatergic and cholinergic signaling.

One-second-long increases in prefrontal cholinergic activity ("transients") were demonstrated previously to be necessary for the incorporation of cues into ongoing cognitive processes ("cue detection"). Nicotine and, more robustly, selective agonists at alpha4beta2* nicotinic acetylcholine receptors (nAChRs) enhance cue detection and attentional performance by augmenting prefrontal cholinergic activity. The present experiments determined the role of beta2-containing and alpha7 nAChRs in the generation of prefrontal cholinergic and glutamatergic transients in vivo. Transients were evoked by nicotine, the alpha4beta2* nAChR agonist ABT-089 [2-methyl-3-(2-(S)-pyrrolindinylmethoxy) pyridine dihydrochloride], or the alpha7 nAChR agonist A-582941 [2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole]. Transients were recorded in mice lacking beta2 or alpha7 nAChRs and in rats after removal of thalamic glutamatergic or midbrain dopaminergic inputs to prefrontal cortex. The main results indicate that stimulation of alpha4beta2* nAChRs evokes glutamate release and that the presence of thalamic afferents is necessary for the generation of cholinergic transients. ABT-089-evoked transients were completely abolished in mice lacking beta2* nAChRs. The amplitude, but not the decay rate, of nicotine-evoked transients was reduced by beta2* knock-out. Conversely, in mice lacking the alpha7 nAChR, the decay rate, but not the amplitude, of nicotine-evoked cholinergic and glutamatergic transients was attenuated. Substantiating the role of alpha7 nAChR in controlling the duration of release events, stimulation of alpha7 nAChR produced cholinergic transients that lasted 10- to 15-fold longer than those evoked by nicotine. alpha7 nAChR-evoked cholinergic transients are mediated in part by dopaminergic activity. Prefrontal alpha4beta2* nAChRs play a key role in evoking and facilitating the transient glutamatergic-cholinergic interactions that are necessary for cue detection and attentional performance.

Purinergic signaling in special senses.

We consider the impact of purinergic signaling on the physiology of the special senses of vision, smell, taste and hearing. Purines (particularly ATP and adenosine) act as neurotransmitters, gliotransmitters and paracrine factors in the sensory retina, nasal olfactory epithelium, taste buds and cochlea. The associated purinergic receptor signaling underpins the sensory transduction and information coding in these sense organs. The P2 and P1 receptors mediate fast transmission of sensory signals and have modulatory roles in the regulation of synaptic transmitter release, for example in the adaptation to sensory overstimulation. Purinergic signaling regulates bidirectional neuron-glia interactions and is involved in the control of blood supply, extracellular ion homeostasis and the turnover of sensory epithelia by modulating apoptosis and progenitor proliferation. Purinergic signaling is an important player in pathophysiological processes in sensory tissues, and has both detrimental (pro-apoptotic) and supportive (e.g. initiation of cytoprotective stress-signaling cascades) effects.