The Importance of the Hook Region of the Cochlea for Bone-Conduction Hearing

For the most part, the coiled shape of the cochlea has been shown to have only minor importance for air-conducted hearing. It is hypothesized, however, that this coiled shape may play a more significant role for the bone-conducted (BC) route of hearing, through inertial forces exerted by the middle ear and cochlear fluid, and that this can be tested by comparing the results of applying BC stimuli in a variety of different directions. A three-dimensional finite element model of a human middle ear coupled to the inner ear was formulated. BC excitations were simulated by applying rigid-body vibrations normal to the surface of the basilar membrane (BM) at 0.8 (d¹), 5.8 (d²), 15.6 (d³), and 33.1 (d⁴) mm from the base of the cochlea, such that relative motions of the fluid within the cochlea produced excitations of the BM. The vibrational direction normal to the BM surface at the base of the cochlea (d¹) produced the highest BM velocity response across all tested frequencies—higher than an excitation direction normal to the BM surface at the nonbasal locations (d²–d⁴), even when the stimulus frequency matched the best frequency for each location. The basal part of the human cochlea features a well-developed hook region, colocated with the cochlear vestibule, that features the largest difference in fluid volume between the scala vestibuli (SV) and scala tympani (ST) found in the cochlea. The proximity of the hook region to the oval and round windows, combined with it having the biggest fluid-volume difference between the SV and ST, is thought to result in a maximization of the pressure difference between the SV and ST for BC stimuli normal to the BM in this region, and consequently a maximization of the resulting BM velocity.     

Quantitative X-ray tomography of the mouse cochlea

Imaging with hard X-rays allows visualizing cochlear structures while maintaining intrinsic qualities of the tissue, including structure and size. With coherent X-rays, soft tissues, including membranes, can be imaged as well as cells making use of the so-called in-line phase contrast. In the present experiments, partially coherent synchrotron radiation has been used for micro-tomography. Three-dimensional reconstructions of the mouse cochlea have been created using the EM3D software and the volume has been segmented in the Amira Software Suite. The structures that have been reconstructed include scala tympani, scala media, scala vestibuli, Reissner's membrane, basilar membrane, tectorial membrane, organ of Corti, spiral limbus, spiral ganglion and cochlear nerve. Cross-sectional areas of the scalae were measured. The results provide a realistic and quantitative reconstruction of the cochlea.     

The Importance of the Hook Region of the Cochlea for Bone-Conduction Hearing

For the most part, the coiled shape of the cochlea has been shown to have only minor importance for air-conducted hearing. It is hypothesized, however, that this coiled shape may play a more significant role for the bone-conducted (BC) route of hearing, through inertial forces exerted by the middle ear and cochlear fluid, and that this can be tested by comparing the results of applying BC stimuli in a variety of different directions. A three-dimensional finite element model of a human middle ear coupled to the inner ear was formulated. BC excitations were simulated by applying rigid-body vibrations normal to the surface of the basilar membrane (BM) at 0.8 (d¹), 5.8 (d²), 15.6 (d³), and 33.1 (d⁴) mm from the base of the cochlea, such that relative motions of the fluid within the cochlea produced excitations of the BM. The vibrational direction normal to the BM surface at the base of the cochlea (d¹) produced the highest BM velocity response across all tested frequencies—higher than an excitation direction normal to the BM surface at the nonbasal locations (d²–d⁴), even when the stimulus frequency matched the best frequency for each location. The basal part of the human cochlea features a well-developed hook region, colocated with the cochlear vestibule, that features the largest difference in fluid volume between the scala vestibuli (SV) and scala tympani (ST) found in the cochlea. The proximity of the hook region to the oval and round windows, combined with it having the biggest fluid-volume difference between the SV and ST, is thought to result in a maximization of the pressure difference between the SV and ST for BC stimuli normal to the BM in this region, and consequently a maximization of the resulting BM velocity.     

Changes in Infrared Spectrum of Nerve during Excitation

MOLECULAR changes that occur in the membrane of nerve during depolarization are important to explain the mechanism of excitation and conduction. During an action potential in nerve the electrical field strength across the membrane undergoes a change of about 10⁵ V cm^?1 which could influence the conformation of membrane molecules possessing a flexible dipole¹. Several methods have been reported for detecting changes with excitation in nerve, muscle and electroplaque^2–11, but have been difficult to interpret. We have therefore used an adaptation of the method of modulation spectroscopy¹², which is based on changes in the absorption spectrum as a result of perturbing the molecular structure^13–16. Our method was based on absorption in the infrared, which occurs for molecular vibrations accompanied by changes in dipole moment.     

An in vitro preparation to access cellular and neuronal components in the mouse inner ear

An in vitro mouse temporal bone preparation has been developed in order to allow the investigation of structures and functions in a living hearing organ. Fluorescent vital probes (a potentiometric styryl dye, RH 795, and a vital dye staining cellular cytoplasm, calcein) were perfused through the scala tympani to stain cellular components of the cochlea. Observations of the cochlear apical turn were performed using a confocal microscope. In spite of the anatomical constraints due to the small size of the mouse cochlea, detailed images were obtained. The sensory cells as well as their innervating nerve fibres were clearly seen. Nerve fibres crossing the tunnel of Corti and projecting to the outer hair cells could also be visualised.     

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies^1,2. Chemotherapy-induced peripheral neuropathy produces symptoms of numbness and paraesthesia in the limbs and may progress to difficulties with fine motor skills and walking, leading to functional impairment. In addition to producing troubling symptoms, chemotherapy-induced neuropathy may limit treatment success leading to dose reduction or early cessation of treatment. Neuropathic symptoms may persist long-term, leaving permanent nerve damage in patients with an otherwise good prognosis³. As chemotherapy is utilised more often as a preventative measure, and survival rates increase, the importance of long-lasting and significant neurotoxicity will increase.There are no established neuroprotective or treatment options and a lack of sensitive assessment methods. Appropriate assessment of neurotoxicity will be critical as a prognostic factor and as suitable endpoints for future trials of neuroprotective agents. Current methods to assess the severity of chemotherapy-induced neuropathy utilise clinician-based grading scales which have been demonstrated to lack sensitivity to change and inter-observer objectivity⁴. Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity^4-6. In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons^7-9.Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity^10-13. Comprising a number of excitability parameters, nerve excitability studies can be used to assess acute neurotoxicity arising immediately following infusion and the development of chronic, cumulative neurotoxicity. Nerve excitability techniques are feasible in the clinical setting, with each test requiring only 5 -10 minutes to complete. Nerve excitability equipment is readily commercially available, and a portable system has been devised so that patients can be tested in situ in the infusion centre setting. In addition, these techniques can be adapted for use in multiple chemotherapies.In patients treated with the chemotherapy oxaliplatin, primarily utilised for colorectal cancer, nerve excitability techniques provide a method to identify patients at-risk for neurotoxicity prior to the onset of chronic neuropathy. Nerve excitability studies have revealed the development of an acute Na⁺ channelopathy in motor and sensory axons^10-13. Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity¹¹. However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients¹⁰. These changes demonstrated a different pattern to those seen acutely following oxaliplatin infusion, and most likely reflect the development of significant axonal damage and membrane potential change in sensory nerves which develops longitudinally during oxaliplatin treatment¹⁰. Significant abnormalities developed during early treatment, prior to any reduction in conventional measures of nerve function, suggesting that excitability parameters may provide a sensitive biomarker.     

Sodium-Dependent Efflux of [3H]GABA from Synaptosomes Probably Related to Mitochondrial Calcium Mobilization

It has been suggested that mitochondria might modify transmitter release through the control of intracellular Ca²⁺levels. Treatments known to inhibit Ca²⁺retention by mitochondria lead to an increased transmitter liberation in the absence of external Ca²⁺, both at the frog neuromuscular junction and from isolated nerve endings. Sodium ions stimulate Ca²⁺efflux from mitochondria isolated from excitable tissues. In the present study, the effect of increasing internal Na⁺ levels on [³H]γ-aminobutyric acid ([³H]GABa) release from isolated nerve endings is reported. Results show that the efflux of [³H]GABA from prelabeled synaptosomes is stimulated by ouabain, veratrine, gramicidin D, and K⁺-free medium, which increase the internal sodium concentration. This effect was not observed when Na⁺ was omitted from the incubation medium and it was independent of external Ca²⁺, the experiments having been performed in a Ca²⁺-free, EGTA-containing medium. Since preincubation of synaptosomes with 2,4-diaminobutyric acid did not prevent the stimulatory effect of increased internal Na⁺ levels on [³H]GABA efflux, it appears to be unrelated to an enhanced activity of the outward carrier-mediated GABA transport. These results suggest that the augmented release of [³H]GABA may be due to an increased Ca²⁺efflux from mitochondria eiicited by the accumulation of Na⁺ at the nerve endings. Sandoval M. E. Sodium-dependent efflux of [³H]GABA from synaptosomes probably related to mitochondrial calcium mobilization. J. Neurochem. 35 , 915–921 (1980).     

Modulation of taurine uptake in the goldfish retina and axonal transport to the tectum¶Effect of crushing the optic nerve or axotomy

Summary. Although there are a great number of studies concerning the uptake of taurine in several tissues, the regulation of taurine transport has not been studied in the retina after lesioning the optic nerve. In the present study, isolated retinal cells of the goldfish retina were used either immediatly after cell suspension or in culture. The high-affinity transport system of [³H]taurine in these cells was sodium-, temperature- and energy-dependent, and was inhibited by hypotaurine and β-alanine, but not by γ-aminobutyric acid. There was a decrease in the maximal velocity (V_max) without modifications in the substrate affinity (K_m) after optic axotomy. These changes were mantained for up to 15 days after the lesion. The results might be the summation of mechanisms for providing extracellular taurine to be taken up by other retinal cells or eye structures, or regulation by the substrate taurine, which increases after lesioning the optic nerve. The in vivo accumulation of [³H]taurine in the retina after intraocular injection of [³H]taurine was affected by crushing the optic nerve or by axotomy. A progressive retinal decrease in taurine transport was observed after crushing the optic nerve, starting at 7 hours after surgery on the nerve. The uptake of [³H]taurine by the tectum was compensated in the animals that were subjected to crushing of the optic nerve, since the concentration of [³H]taurine was only different from the control value 24 hours after the lesion, indicating an efficient transport by the remaining axons. On the contrary, the low levels of [³H]taurine in the tectum after axotomy might be an index of the non-axonal origin of taurine in the tectum. Axonal transport was illustrated by the differential presence of [³H]taurine in the intact or crushed optic nerve. The uptake of [³H]taurine into retinal cells in culture in the absence or in the presence of taurine might indicate the existence of an adaptive regulation of taurine transport in this tissue, however taurine transport probably differentially occurs in specific populations of retinal cells. The use of a purified preparation of cells might be useful for future studies on the modulation of taurine transport by taurine in the retina and its role during regeneration. Received June 11, 1999/Accepted August 31, 1999     

Is evolutionary biology becoming too politically correct? A reflection on the scala naturae,phylogenetically basal clades,anatomically plesiomorphic taxa,and ‘lower’ animals

The notion of scala naturae dates back to thinkers such as Aristotle, who placed plants below animals and ranked the latter along a graded scale of complexity from ‘lower’ to ‘higher’ animals, such as humans. In the last decades, evolutionary biologists have tended to move from one extreme (i.e. the idea of scala naturae or the existence of a general evolutionary trend in complexity from ‘lower’ to “higher” taxa, with Homo sapiens as the end stage) to the other, opposite, extreme (i.e. to avoid using terms such as ‘phylogenetically basal’ and ‘anatomically plesiomorphic’ taxa, which are seen as the undesired vestige of old teleological theories). The latter view tries to avoid any possible connotations with the original anthropocentric idea of a scala naturae crowned by man and, in that sense, it can be regarded as a more politically correct view. In the past years and months there has been renewed interest in these topics, which have been discussed in various papers and monographs that tend to subscribe, in general, to the points defended in the more politically correct view. Importantly, most evolutionary and phylogenetic studies of tetrapods and other vertebrates, and therefore most discussions on the scala naturae and related issues have been based on hard tissue and, more recently, on molecular data. Here we provide the first discussion of these topics based on a comparative myological study of all the major vertebrate clades and of myological cladistic and Bayesian phylogenetic analyses of bony fish and tetrapods, including Primates. We specifically (i) contradict the notions of a scala naturae or evolutionary progressive trends leading to more complexity in ‘higher’ animals and culminating in Homo sapiens, and (ii) stress that the refutation of these old notions does not necessarily mean that one should not keep using the terms ‘phylogenetically basal’ and particularly ‘anatomically plesiomorphic’ to refer to groups such as the urodeles within the Tetrapoda, or the strepsirrhines and lemurs within the Primates, for instance. This review will contribute to improving our understanding of these broad evolutionary issues and of the evolution of the vertebrate Bauplans, and hopefully will stimulate future phylogenetic, evolutionary and developmental studies of these clades.     

TRPC3 ion channel subunit immunolocalization in the cochlea

Canonical transient receptor potential (TRPC) subunits assemble as tetramers to form ion channels with high calcium (Ca²⁺) permeability. Here, we investigated the possibility that TRPC3 ion channels are broadly expressed in the adult guinea pig and mouse cochleae. Using immunofluorescence, pronounced labeling occurred in the spiral ganglion (SG) neurons, inner hair cells (IHC), outer hair cells (OHC) and epithelial cells lining scala media. TRPC3 expression was homogeneous in the SG throughout the cochlea. In contrast, there was marked spatial variation in the immunolabeling in the cochlear hair cells with respect to location. This likely relates to the tonotopy of these cells. TRPC3 immunolabeling was more pronounced in the IHC than OHC. Both basal region IHC and OHC had higher TRPC3 expression levels than the corresponding cells from the apical region of the cochlea. These data suggest that TRPC3 ion channels contribute to Ca²⁺ homeostasis associated with the hair cells, with higher ion fluxes in more basal regions of the cochlea, and may also be a significant pathway for Ca²⁺ entry associated with auditory neurotransmission via the SG neurons. TRPC3 expression was also identified within the spiral limbus region, inner and outer sulcus, but without evidence for spatial variation in expression level. Expression in these gap junction-coupled epithelial cells lining scala media is indicative of a contribution of TRPC3 channels to cochlear electrochemical homeostasis.     

POLARIZATION AND ELECTRON MICROSCOPE STUDY OF FROG NERVE AXOPLASM

1. The submicroscopic organization of nerve axons from R. pipiens and R. catesbiana has been studied by means of polarizing and electron microscopes. 2. In measurements on a series of 85 fresh myelinated axons from which the sheaths had been removed average values were obtained for the total birefringence, +2.5 x 10^–4, the form birefringence, +1.4 x 10^–4, and the refractive index of the oriented component, 1.523. The average partial volume occupied by axially oriented filaments was computed to be 0.69 per cent. 3. Electron micrographs of fixed myelinated axons demonstrate an average of 93 axially oriented neuroprotofibrils per square micron of cross-section. The neuroprotofibrils are approximately 90 A in diameter, of indefinite length, and occupy a computed partial volume of 0.59 per cent. 4. Mitochondria, neuroprotofibrils, endoplasmic reticulum, and dense particles are seen in electron micrographs of both myelinated and unmyelinated nerve axons. 5. It is concluded that the neuroprotofibrils are present in the living nerve, that they play an important but undetermined role in nerve function, and that these structures are not an artifact of osmium tetroxide fixation.     

Ultrastructural relationship between monoamine- and TRH-containing axons in the rat median eminence as revealed by combined autoradiography and immunocytochemistry in the same tissue section

Summary The correlation of dopamine (DA)-, noradrenaline (NA)- or serotonin (5HT)-containing neurons and thyrotropin releasing hormone (TRH)-containing neurons in the median eminence of the rat, as well as the coexistence of monoamines (MA) and TRH in the neurons, were examined by subjecting ultrathin sections to a technique that combines MA autoradiography and TRH immunocytochemistry. The distribution and localization of silver grains after ³H-MA injection were examined by application of circle analysis on the autoradiographs.TRH-like immunoreactive nerve terminals containing the immunoreactive dense granular vesicles were found to have an intimate contact with monoaminergic terminals labeled after ³H-DA, ³H-NA or ³H-5HT infusion in the vicinity of the primary portal capillaries in the median eminence. Synapses between TRH-like immunoreactive axons and MA axons labeled with silver grains, however, have not been observed to date. Findings suggesting the coexistence of TRH and MA in the same nerve terminals or the uptake of ³H-MA into TRH-like immunoreactive nerve terminals, where silver grains after ³H-MA injection were concurrently localized in TRH-like immunoreactive nerve terminals, were rarely observed in the median eminence. Percentages of the nerve terminals containing both immunoreactive granular vesicles and silver grains after ³H-MA injection to total nerve terminals labeled after ³H-MA infusion silver grains were equally very low in ³H-DA, ³H-NA or ³H-5HT, amounting to less than 6.1%.This work was supported in part by grant-in-aid for scientific research from the Japan Ministry of Education (No. 557018).     

Human Vagus Nerve Branching in the Cervical Region

BackgroundVagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation.ResultsCervical vagus nerve branching was observed in 29% of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79 mm vs. 3.78 mm) and cross-sections (7.24 mm² vs. 5.28 mm²).DiscussionCervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation.     

Nitric oxide and antioxidant status in glucose and oxygen deprived neonatal and adult rat brain synaptosomes

Nitric oxide (NO) has been implicated in the process of cerebral ischemia/reperfusion injury. We have examined the production of NO, as reflected by nitrite (NO₂ ⁻)+nitrate (NO₃ ⁻) accumulation, from synaptosomes isolated from neonatal or adult rat brain and subjected to a period of glucose and oxygen deprivation. There was a significant increase in the amount of NO₂ ⁻+NO₃ ⁻ production from adult synaptosomes under these conditions, whereas there was no difference compared to control in the production of NO₂ ⁻+NO₃ ⁻ from the neonatal synaptosomes. The total antioxidant status of the synaptosomes at these different stages of brain development was found to be the same. These data suggest that the vulnerability of the adult brain to ischemia/reperfusion injury may be associated with the production of NO from nerve terminals. The ratios of antioxidant capacity to NO production under such conditions have been shown here to be different between the neonatal and adult nerve terminals. Thus the well documented resistance of neonatal brain to ischemia/reperfusion injury may involve the neonatal nerve terminal being under less oxidative stress than the adult.     

Fangchinoline inhibits glutamate release from rat cerebral cortex nerve terminals (synaptosomes)

Fangchinoline, an active component of radix stephaniae tetrandrinea, has been shown to possess neuroprotective properties. It has been reported that excessive glutamate release has been proposed to be involved in the pathogenesis of several neurological diseases. The primary purpose of the present study was to investigate the effect of fangchinoline on glutamate release in rat cerebral cortex nerve terminals and to explore the possible mechanism. Fangchinoline inhibited the release of glutamate evoked by 4-aminopyridine (4-AP) in a concentration-dependent manner, and this phenomenon resulted from a reduction of vesicular exocytosis but not from an inhibition of Ca²⁺-independent efflux via glutamate transporter. Fangchinoline did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization, but significantly reduced depolarization-induced increase in [Ca²⁺]_C. Fangchinoline-mediated inhibition of glutamate release was significantly prevented by the N- and P/Q-type Ca²⁺ channel blocker ω-conotoxin MVIIC, and by the PKC inhibitors, GF109203X and Ro318220. In addition, the glutamate release mediated by direct Ca²⁺ entry with Ca²⁺ ionophore (ionomycin) was unaffected by fangchinoline, which suggests that the inhibitory effect of fangchinoline is not due to directly interfering with the release process at some point subsequent to Ca²⁺ influx. These results suggest that fangchinoline inhibits glutamate release from the rat cortical synaptosomes through the suppression of voltage-dependent Ca²⁺ channel activity and subsequent reduces Ca²⁺ entry into nerve terminals, rather than any upstream effect on nerve terminal excitability. This inhibition appears to involve the suppression of PKC signal transduction pathway. This finding may explain the neuroprotective effects of fangchinoline against neurotoxicity.     

Histofluorescence study and biochemical assay of catecholamines (Dopamine and Noradrenaline) during the course of arm-tip regeneration in the starfish,Asterina gibbosa (Echinodermata,Asteroidea)

Summary In the starfish, Asterina gibbosa, the histofluorescence method gives evidence of an aminergic activity in the course of arm-tip regeneration. This activity can be detected as variations in the localization and intensity of a green fluorescence in the nerve structures of the arm, the radial nerve, and the circumoral nerve ring connected to it. Biochemical assays reveal that dopamine levels increase on the 2^nd and 4^th days of regeneration, when the blastema is forming and when differentiation commences. The level of noradrenaline also increases on the 2^nd day after amputation of the arm.     

Electric-Field-Induced Shifts in the Infrared Spectrum of Conducting Nerve Axons

Difference spectra between resting and excited nerve in the infrared region between 2000 and 1000 cm^-1 have been examined with a resolution of 0.5 cm^-1. Spectra were obtained with a modified Perkin-Elmer model 521 grating infrared spectrophotometer (Perkin-Elmer Corp., Instrument Div., Norwalk, Conn.), and the signal-to-noise (S/N) ratio was improved by time averaging and digital smoothing. Peaks occurring in the regions around 1030 and 1066 cm^-1 are identified as P-O-C stretch, at 1410-1414 cm^-1 as C-H deformation, and at 1750 cm^-1 as carbonyl stretch. The difference peaks appear to be due to a shift of about 1 cm^-1 in the absorption band to lower frequencies for the three lower frequency bands and to a higher frequency for 1750 cm^-1 band. Since the difference peaks appear when the nerve is modulated by a propagated action potential it is concluded that the changing electrical field across the nerve membrane is perturbing the absorption spectrum. From evidence presented it appears likely that these difference peaks are due to phospholipids in the nerve membrane and that they may be related to conformational changes associated with membrane permeability.     

Function of Catecholamine-containing Neurones in Mammalian Central Nervous System

SEVERAL chemical substances are involved in synaptic transmission in the mammalian central nervous system^1–3. The Falck-Hillarp technique⁴ has demonstrated noradrenaline, dopamine and 5-hydroxytryptamine within nerve cell bodies and terminals^5,6 and the belief that these amines act as neurohumours is strengthened by observations that nerve fibre activation leads to their release from the terminals^7,8. Histo-chemical evidence suggests that discrete systems of neurones can be identified by their content of particular amines and it seems possible that such neurohumorally homogeneous systems have a functional as well as a chemical identity. Before the anatomical distribution of amine-containing neurones had been described, Brodie and Shore⁹ proposed that noradrenaline functions as the central neurohumour of the sympathetic and 5-hydroxytryptamine of the parasympathetic system. This suggestion has not been supported by anatomical evidence; the amine-containing neurones form systems of small diameter fibres of very diffuse terminal distribution, which do not correspond to recognized ascending or descending pathways^5,6, although amine-containing neurones in invertebrates have been identified as sensory systems¹⁰.