RESUMEN
Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.
Asunto(s)
Diferenciación Celular/fisiología , Células Ciliadas Auditivas/fisiología , Células Ciliadas Vestibulares/fisiología , Mecanorreceptores/fisiología , Regeneración/fisiología , Sáculo y Utrículo/fisiología , Animales , Fenómenos Electrofisiológicos/fisiología , Células Ciliadas Auditivas/citología , Células Ciliadas Vestibulares/citología , Mecanorreceptores/citología , Ratones Transgénicos , Sáculo y Utrículo/citología , Transmisión Sináptica/fisiologíaRESUMEN
Spiral ganglion neurons (SGNs) form single synapses on inner hair cells (IHCs), transforming sound-induced IHC receptor potentials into trains of action potentials. SGN neurons are classified by spontaneous firing rates as well as their threshold response to sound intensity levels. We investigated the hypothesis that synaptic specializations underlie mouse SGN response properties and vary with pillar versus modiloar synapse location around the hair cell. Depolarizing hair cells with 40 mM K+ increased the rate of postsynaptic responses. Pillar synapses matured later than modiolar synapses. Excitatory postsynaptic current (EPSC) amplitude, area, and number of underlying events per EPSC were similar between synapse locations at steady state. However, modiolar synapses produced larger monophasic EPSCs when EPSC rates were low and EPSCs became more multiphasic and smaller in amplitude when rates were higher, while pillar synapses produced more monophasic and larger EPSCs when the release rates were higher. We propose that pillar and modiolar synapses have different operating points. Our data provide insight into underlying mechanisms regulating EPSC generation.NEW & NOTEWORTHY Data presented here provide the first direct functional evidence of late synaptic maturation of the hair cell- spiral ganglion neuron synapse, where pillar synapses mature after postnatal day 20. Data identify a presynaptic difference in release during stimulation. This difference may in part drive afferent firing properties.
Asunto(s)
Cóclea/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Células Ciliadas Auditivas Internas/fisiología , Neuronas/fisiología , Ganglio Espiral de la Cóclea/fisiología , Sinapsis/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ganglio Espiral de la Cóclea/crecimiento & desarrolloRESUMEN
The synapse between inner hair cells and auditory nerve fiber dendrites shows large excitatory postsynaptic currents (EPSCs), which are either monophasic or multiphasic. Multiquantal or uniquantal (flickering) release of neurotransmitter has been proposed to underlie the unusual multiphasic waveforms. Here the nature of multiphasic waveforms is analyzed using EPSCs recorded in vitro in rat afferent dendrites. Spontaneous EPSCs were deconvolved into a sum of presumed release events having monophasic EPSC waveforms. Results include, first, the charge of EPSCs is about the same for multiphasic versus monophasic EPSCs. Second, EPSC amplitudes decline with the number of release events per EPSC. Third, there is no evidence of a mini-EPSC. Most results can be accounted for by versions of either uniquantal or multiquantal release. However, serial neurotransmitter release in multiphasic EPSCs shows properties that are not fully explained by either model, especially that the amplitudes of individual release events are established at the beginning of a multiphasic EPSC, constraining possible models of vesicle release.NEW & NOTEWORTHY How do monophasic and multiphasic waveshapes arise in auditory-nerve dendrites; mainly are they uniquantal, arising from release of a single vesicle, or multiquantal, requiring several vesicles? The charge injected by excitatory postsynaptic currents (EPSCs) is the same for monophasic or multiphasic EPSCs, supporting uniquantal release. Serial adaptation of responses to sequential EPSCs favors a multiquantal model. Finally, neurotransmitter partitioning into similar sized release boluses occurs at the first bolus in the EPSC, not easily explained with either model.
Asunto(s)
Nervio Coclear/fisiología , Dendritas/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Células Ciliadas Auditivas Internas/fisiología , Sinapsis/fisiología , Animales , Femenino , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
In macaques, the middle lateral auditory cortex (ML) is a belt region adjacent to the primary auditory cortex (A1) and believed to be at a hierarchically higher level. Although ML single-unit responses have been studied for several auditory stimuli, the ability of ML cells to encode amplitude modulation (AM)-an ability that has been widely studied in A1-has not yet been characterized. Here, we compared the responses of A1 and ML neurons to amplitude-modulated (AM) noise in awake macaques. Although several of the basic properties of A1 and ML responses to AM noise were similar, we found several key differences. ML neurons were less likely to phase lock, did not phase lock as strongly, and were more likely to respond in a nonsynchronized fashion than A1 cells, consistent with a temporal-to-rate transformation as information ascends the auditory hierarchy. ML neurons tended to have lower temporally (phase-locking) based best modulation frequencies than A1 neurons. Neurons that decreased their firing rate in response to AM noise relative to their firing rate in response to unmodulated noise became more common at the level of ML than they were in A1. In both A1 and ML, we found a prevalent class of neurons that usually have enhanced rate responses relative to responses to the unmodulated noise at lower modulation frequencies and suppressed rate responses relative to responses to the unmodulated noise at middle modulation frequencies.NEW & NOTEWORTHY ML neurons synchronized less than A1 neurons, consistent with a hierarchical temporal-to-rate transformation. Both A1 and ML had a class of modulation transfer functions previously unreported in the cortex with a low-modulation-frequency (MF) peak, a middle-MF trough, and responses similar to unmodulated noise responses at high MFs. The results support a hierarchical shift toward a two-pool opponent code, where subtraction of neural activity between two populations of oppositely tuned neurons encodes AM.
Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Neuronas/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Femenino , Macaca mulatta , MasculinoRESUMEN
Most models of auditory cortical (AC) population coding have focused on primary auditory cortex (A1). Thus our understanding of how neural coding for sounds progresses along the cortical hierarchy remains obscure. To illuminate this, we recorded from two AC fields: A1 and middle lateral belt (ML) of rhesus macaques. We presented amplitude-modulated (AM) noise during both passive listening and while the animals performed an AM detection task ("active" condition). In both fields, neurons exhibit monotonic AM-depth tuning, with A1 neurons mostly exhibiting increasing rate-depth functions and ML neurons approximately evenly distributed between increasing and decreasing functions. We measured noise correlation (rnoise) between simultaneously recorded neurons and found that whereas engagement decreased average rnoise in A1, engagement increased average rnoise in ML. This finding surprised us, because attentive states are commonly reported to decrease average rnoise We analyzed the effect of rnoise on AM coding in both A1 and ML and found that whereas engagement-related shifts in rnoise in A1 enhance AM coding, rnoise shifts in ML have little effect. These results imply that the effect of rnoise differs between sensory areas, based on the distribution of tuning properties among the neurons within each population. A possible explanation of this is that higher areas need to encode nonsensory variables (e.g., attention, choice, and motor preparation), which impart common noise, thus increasing rnoise Therefore, the hierarchical emergence of rnoise-robust population coding (e.g., as we observed in ML) enhances the ability of sensory cortex to integrate cognitive and sensory information without a loss of sensory fidelity.NEW & NOTEWORTHY Prevailing models of population coding of sensory information are based on a limited subset of neural structures. An important and under-explored question in neuroscience is how distinct areas of sensory cortex differ in their population coding strategies. In this study, we compared population coding between primary and secondary auditory cortex. Our findings demonstrate striking differences between the two areas and highlight the importance of considering the diversity of neural structures as we develop models of population coding.
Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Neuronas/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Atención/fisiología , Femenino , Macaca mulatta , Masculino , Microelectrodos , Detección de Señal Psicológica/fisiologíaRESUMEN
Noise correlations (r(noise)) between neurons can affect a neural population's discrimination capacity, even without changes in mean firing rates of neurons. r(noise), the degree to which the response variability of a pair of neurons is correlated, has been shown to change with attention with most reports showing a reduction in r(noise). However, the effect of reducing r(noise) on sensory discrimination depends on many factors, including the tuning similarity, or tuning correlation (r(tuning)), between the pair. Theoretically, reducing r(noise) should enhance sensory discrimination when the pair exhibits similar tuning, but should impair discrimination when tuning is dissimilar. We recorded from pairs of neurons in primary auditory cortex (A1) under two conditions: while rhesus macaque monkeys (Macaca mulatta) actively performed a threshold amplitude modulation (AM) detection task and while they sat passively awake. We report that, for pairs with similar AM tuning, average r(noise) in A1 decreases when the animal performs the AM detection task compared with when sitting passively. For pairs with dissimilar tuning, the average r(noise) did not significantly change between conditions. This suggests that attention-related modulation can target selective subcircuits to decorrelate noise. These results demonstrate that engagement in an auditory task enhances population coding in primary auditory cortex by selectively reducing deleterious r(noise) and leaving beneficial r(noise) intact.
Asunto(s)
Potenciales de Acción/fisiología , Corteza Auditiva/citología , Percepción Auditiva/fisiología , Toma de Decisiones/fisiología , Discriminación en Psicología/fisiología , Células Receptoras Sensoriales/fisiología , Estimulación Acústica , Análisis de Varianza , Animales , Femenino , Modelos Logísticos , Macaca mulatta , Masculino , RecompensaRESUMEN
We recorded from middle lateral belt (ML) and primary (A1) auditory cortical neurons while animals discriminated amplitude-modulated (AM) sounds and also while they sat passively. Engagement in AM discrimination improved ML and A1 neurons' ability to discriminate AM with both firing rate and phase-locking; however, task engagement affected neural AM discrimination differently in the two fields. The results suggest that these two areas utilize different AM coding schemes: a "single mode" in A1 that relies on increased activity for AM relative to unmodulated sounds and a "dual-polar mode" in ML that uses both increases and decreases in neural activity to encode modulation. In the dual-polar ML code, nonsynchronized responses might play a special role. The results are consistent with findings in the primary and secondary somatosensory cortices during discrimination of vibrotactile modulation frequency, implicating a common scheme in the hierarchical processing of temporal information among different modalities. The time course of activity differences between behaving and passive conditions was also distinct in A1 and ML and may have implications for auditory attention. At modulation depths ≥ 16% (approximately behavioral threshold), A1 neurons' improvement in distinguishing AM from unmodulated noise is relatively constant or improves slightly with increasing modulation depth. In ML, improvement during engagement is most pronounced near threshold and disappears at highly suprathreshold depths. This ML effect is evident later in the stimulus, and mainly in nonsynchronized responses. This suggests that attention-related increases in activity are stronger or longer-lasting for more difficult stimuli in ML.
Asunto(s)
Corteza Auditiva/fisiología , Discriminación en Psicología/fisiología , Percepción Sonora/fisiología , Neuronas/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Femenino , Macaca mulatta , Masculino , Microelectrodos , Pruebas Neuropsicológicas , Curva ROC , Procesamiento de Señales Asistido por Computador , Factores de TiempoRESUMEN
We recorded from middle-lateral (ML) and primary (A1) auditory cortex while macaques discriminated amplitude-modulated (AM) noise from unmodulated noise. Compared with A1, ML had a higher proportion of neurons that encoded increasing AM depth by decreasing their firing rates ("decreasing" neurons), particularly with responses that were not synchronized to the modulation. Choice probability (CP) analysis revealed that A1 and ML activity were different during the first half of the test stimulus. In A1, significant CP began before the test stimulus, remained relatively constant (or increased slightly) during the stimulus, and increased greatly within 200 ms of lever release. Neurons in ML behaved similarly, except that significant CP disappeared during the first half of the stimulus and reappeared during the second half and prerelease periods. CP differences between A1 and ML depend on neural response type. In ML (but not A1), when activity was lower during the first half of the stimulus in nonsynchronized, decreasing neurons, the monkey was more likely to report AM. Neurons that both increased firing rate with increasing modulation depth ("increasing" neurons) and synchronized their responses to AM had similar choice-related activity dynamics in ML and A1. These results suggest that, when ascending the auditory system, there is a transformation in coding AM from primarily synchronized increasing responses in A1 to nonsynchronized and dual (increasing/decreasing) coding in ML. This sensory transformation is accompanied by changes in the timing of activity related to choice, suggesting functional differences between A1 and ML related to attention and/or behavior.
Asunto(s)
Corteza Auditiva/citología , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Conducta de Elección/fisiología , Neuronas/fisiología , Sonido , Estimulación Acústica , Potenciales de Acción/fisiología , Animales , Discriminación en Psicología , Femenino , Lateralidad Funcional , Macaca mulatta , Masculino , Curva ROC , Tiempo de Reacción , Estadísticas no ParamétricasRESUMEN
The vestibular short-latency evoked potential (VsEP) reflects the activity of irregular vestibular afferents and their target neurons in the brain stem. Attenuation of trial-averaged VsEP waveforms is widely accepted as an indicator of vestibular dysfunction, however, more quantitative analyses of VsEP waveforms could reveal underlying neural properties of VsEP waveforms. Here, we present a time-frequency analysis of the VsEP with a wavelet transform on a single-trial basis, which allows us to examine trial-by-trial variability in the strength of VsEP waves as well as their temporal coherence across trials. Using this method, we examined changes in the VsEP following 110 dB SPL noise exposure in rats. We found detectability of head jerks based on the power of wavelet transform coefficients was significantly reduced 1 day after noise exposure but recovered nearly to pre-exposure level in 3 - 7 days and completely by 28 days after exposure. Temporal coherence of VsEP waves across trials was also significantly reduced on 1 day after exposure but recovered with a similar time course. Additionally, we found a significant reduction in the number of calretinin-positive calyces in the sacculi collected 28 days after noise exposure. Furthermore, the number of calretinin-positive calyces was significantly correlated with the degree of reduction in temporal coherence and/or signal detectability of the smallest-amplitude jerks. This new analysis of the VsEP provides more quantitative descriptions of noise-induced changes as well as new insights into potential mechanisms underlying noise-induced vestibular dysfunction. Significance Statement: Our study presents a new method of VsEP quantification using wavelet transform on a single-trial basis. It also describes a novel approach to determine the stimulus threshold of the VsEP based on signal-detection theory and Rayleigh statistics. The present analysis could also be applied to analysis of auditory brain stem response (ABR). Thus, it has the potential to provide new insights into the physiological properties that underlie peripheral vestibular and auditory dysfunction.
RESUMEN
The effect of attention on single neuron responses in the auditory system is unresolved. We found that when monkeys discriminated temporally amplitude modulated (AM) from unmodulated sounds, primary auditory cortical (A1) neurons better discriminated those sounds than when the monkeys were not discriminating them. This was observed for both average firing rate and vector strength (VS), a measure of how well neurons temporally follow the stimulus' temporal modulation. When data were separated by nonsynchronized and synchronized responses, the firing rate of nonsynchronized responses best distinguished AM- noise from unmodulated noise, followed by VS for synchronized responses, with firing rate for synchronized neurons providing the poorest AM discrimination. Firing rate-based AM discrimination for synchronized neurons, however, improved most with task engagement, showing that the least sensitive code in the passive condition improves the most with task engagement. Rate coding improved due to larger increases in absolute firing rate at higher modulation depths than for lower depths and unmodulated sounds. Relative to spontaneous activity (which increased with engagement), the response to unmodulated sounds decreased substantially. The temporal coding improvement--responses more precisely temporally following a stimulus when animals were required to attend to it--expands the framework of possible mechanisms of attention to include increasing temporal precision of stimulus following. These findings provide a crucial step to understanding the coding of temporal modulation and support a model in which rate and temporal coding work in parallel, permitting a multiplexed code for temporal modulation, and for a complementary representation of rate and temporal coding.
Asunto(s)
Potenciales de Acción/fisiología , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Discriminación en Psicología/fisiología , Neuronas/fisiología , Percepción del Tiempo/fisiología , Animales , Femenino , Macaca mulatta , MasculinoRESUMEN
Recent evidence is reshaping the view of primary auditory cortex (A1) from a unisensory area to one more involved in dynamically integrating multisensory- and task-related information. We found A1 single- (SU) and multiple-unit (MU) activity correlated with macaques' choices in an amplitude modulation (AM) discrimination task. Animals were trained to discriminate AM noise from unmodulated noise by releasing a lever for AM noise and holding down the lever for unmodulated noise. Activity for identical stimuli was compared between trials where the animals reported AM and trials where they did not. We found 47.4% of MUs and 22.8% of SUs significantly increased firing shortly before the animal's behavioral response to report AM when compared to the equivalent time period on trials where AM was not reported. Activity was also linked to lever release in a different task context, suggesting A1 modulation by somatosensory, or efference copy, input. When spikes were counted only during the stimulus, 19.6% of MUs and 13.8% of SUs increased firing rate when animals reported AM compared to when they did not, suggesting an attentional effect, or that A1 activity can be used by higher decision areas, or that such areas provide feedback to A1. Activity associated with AM reporting was correlated with a unit's AM sensitivity, suggesting AM sensitive neurons' involvement in task performance. A1 neurons' phase locking to AM correlated more weakly (compared to firing rate) with the animals' report of AM, suggesting a preferential role for rate-codes in A1 for this AM discrimination task.
Asunto(s)
Estimulación Acústica , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Juicio/fisiología , Estimulación Acústica/métodos , Potenciales de Acción , Animales , Mapeo Encefálico/métodos , Femenino , Macaca mulatta , Masculino , Distribución AleatoriaRESUMEN
Previous studies and models of perceptual decision making have largely focused on binary choices. However, we often have to choose from multiple alternatives. To study the neural mechanisms underlying multialternative decision making, we have asked human subjects to make perceptual decisions between multiple possible directions of visual motion. Using a multicomponent version of the random-dot stimulus, we were able to control experimentally how much sensory evidence we wanted to provide for each of the possible alternatives. We demonstrate that this task provides a rich quantitative dataset for multialternative decision making, spanning a wide range of accuracy levels and mean response times. We further present a computational model that can explain the structure of our behavioral dataset. It is based on the idea of a race between multiple integrators to a decision threshold. Each of these integrators accumulates net sensory evidence for a particular choice, provided by linear combinations of the activities of decision-relevant pools of sensory neurons.
Asunto(s)
Toma de Decisiones/fisiología , Percepción de Movimiento/fisiología , Estimulación Luminosa/métodos , Adulto , Humanos , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles.
Asunto(s)
Vesículas Citoplasmáticas/metabolismo , Células Ciliadas Auditivas/fisiología , Neuronas Aferentes/fisiología , Sinapsis/fisiología , Oxidorreductasas de Alcohol , Animales , Proteínas Co-Represoras , Proteínas de Unión al ADN/deficiencia , Ratones , Ratones Noqueados , Fosfoproteínas/deficiencia , Transducción de SeñalRESUMEN
A serum raised against octopamine reveals in cockroaches and honey bees structurally comparable systems of perikarya and their extensive yet discrete systems of arborizations in neuropils. Numerous and prominent clusters of lateral cell bodies in the brain as well as many midline perikarya provide octopamine-like immunoreactive processes to circumscribed regions of the subesophageal ganglion, antennal lobe glomeruli, optic neuropils, and neuropils of the protocerebrum. There is dense octopaminergic innervation in the protocerebral bridge and ellipsoid body of the central complex. The antennal lobes are supplied by at least three octopamine-immunoreactive neurons. In contrast, the mushroom bodies show the fewest immunoreactive elements. In Apis a single axon supplies sparse immunoreactive processes to the calyces' basal ring, collar, and lip. A diffuse arrangement of immunoreactive processes invades all zones of the mushroom body calyces in Periplaneta. These processes derive from an ascending axon ascribed to a dorsal unpaired median neuron at the maxillary segment of the subesophageal ganglion. In both taxa octopamine-immunoreactive processes invade only the gamma lobes of the mushroom bodies, omitting their other divisions. The present observations are discussed with respect to possible roles of octopamine in sensory integration and association.
Asunto(s)
Encéfalo/metabolismo , Ganglios de Invertebrados/metabolismo , Octopamina/metabolismo , Animales , Abejas/anatomía & histología , Encéfalo/citología , Cucarachas/anatomía & histología , Ganglios de Invertebrados/citología , Inmunohistoquímica/métodos , Lisina/análogos & derivados , Lisina/metabolismo , Vías Nerviosas/metabolismo , Neuronas/metabolismo , Neurópilo/metabolismo , Especificidad de la EspecieRESUMEN
Previous observations show that humans outperform non-human primates on some temporally-based auditory discrimination tasks, suggesting there are species differences in the proficiency of auditory temporal processing among primates. To further resolve these differences we compared the abilities of rhesus macaques and humans to detect sine-amplitude modulation (AM) of a broad-band noise carrier as a function of both AM frequency (2.5 Hz-2 kHz) and signal duration (50-800 ms), under similar testing conditions. Using a go/no-go AM detection task, we found that macaques were less sensitive than humans at the lower frequencies and shorter durations tested but were as, or slightly more, sensitive at higher frequencies and longer durations. Humans had broader AM tuning functions, with lower frequency regions of peak sensitivity (10-60 Hz) than macaques (30-120 Hz). These results support the notion that there are species differences in temporal processing among primates, and underscore the importance of stimulus duration when making cross-species comparisons for temporally-based tasks.