RESUMEN
Sensory receptor noise corrupts sensory signals, contributing to imperfect perception and dictating central processing strategies. For example, noise in rod phototransduction limits our ability to detect light, and minimizing the impact of this noise requires precisely tuned nonlinear processing by the retina. But detection sensitivity is only one aspect of night vision: prompt and accurate behavior also requires that rods reliably encode the timing of photon arrivals. We show here that the temporal resolution of responses of primate rods is much finer than the duration of the light response and identify the key limiting sources of transduction noise. We also find that the thermal activation rate of rhodopsin is lower than previous estimates, implying that other noise sources are more important than previously appreciated. A model of rod single-photon responses reveals that the limiting noise relevant for behavior depends critically on how rod signals are pooled by downstream neurons. NEW & NOTEWORTHY Many studies have focused on the visual system's ability to detect photons, but not on its ability to encode the relative timing of detected photons. Timing is essential for computations such as determining the velocity of moving objects. Here we examine the timing precision of primate rod photoreceptor responses and show that it is more precise than previously appreciated. This motivates an evaluation of whether scotopic vision approaches limits imposed by rod temporal resolution.
Asunto(s)
Fotones , Células Fotorreceptoras Retinianas Bastones/fisiología , Visión Ocular/fisiología , Animales , Conducta Compulsiva , Modelos Lineales , Macaca fascicularis , Redes Neurales de la Computación , Dinámicas no Lineales , Papio anubis , Estimulación Luminosa , Rodopsina/metabolismo , Umbral Sensorial/fisiología , Procesamiento de Señales Asistido por Computador , Factores de Tiempo , Técnicas de Cultivo de TejidosRESUMEN
Maintaining physiological pH is required for survival, and exposure to alkaline chemicals such as ammonia (smelling salts) elicits severe pain and inflammation through unknown mechanisms. TRPV1, the capsaicin receptor, is an integrator of noxious stimuli including heat and extracellular acidic pH. Here, we report that ammonia activates TRPV1, TRPA1 (another polymodal nocisensor), and other unknown receptor(s) expressed in sensory neurons. Ammonia and intracellular alkalization activate TRPV1 through a mechanism that involves a cytoplasmic histidine residue, not used by other TRPV1 agonists such as heat, capsaicin or low pH. Our studies show that TRPV1 detects both acidic and basic deviations from homeostatic pH.
Asunto(s)
Ácidos/farmacología , Cloruro de Amonio/farmacología , Células Receptoras Sensoriales/efectos de los fármacos , Canales Catiónicos TRPV/metabolismo , Animales , Calcio/metabolismo , Capsaicina/farmacología , Línea Celular Transformada , Ganglios Espinales/citología , Humanos , Concentración de Iones de Hidrógeno , Proteínas Luminiscentes/genética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Biológicos , Mutagénesis Sitio-Dirigida/métodos , Técnicas de Placa-Clamp , Pirazinas/farmacología , Piridinas/farmacología , Fármacos del Sistema Sensorial/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/deficiencia , Transfección/métodosRESUMEN
Sensory encoding in spiking neurons depends on both the integration of sensory inputs and the intrinsic dynamics and variability of spike generation. We show that the stimulus selectivity, reliability, and timing precision of primate retinal ganglion cell (RGC) light responses can be reproduced accurately with a simple model consisting of a leaky integrate-and-fire spike generator driven by a linearly filtered stimulus, a postspike current, and a Gaussian noise current. We fit model parameters for individual RGCs by maximizing the likelihood of observed spike responses to a stochastic visual stimulus. Although compact, the fitted model predicts the detailed time structure of responses to novel stimuli, accurately capturing the interaction between the spiking history and sensory stimulus selectivity. The model also accounts for the variability in responses to repeated stimuli, even when fit to data from a single (nonrepeating) stimulus sequence. Finally, the model can be used to derive an explicit, maximum-likelihood decoding rule for neural spike trains, thus providing a tool for assessing the limitations that spiking variability imposes on sensory performance.
Asunto(s)
Potenciales de Acción , Modelos Neurológicos , Modelos Estadísticos , Células Ganglionares de la Retina/fisiología , Animales , Macaca , Estimulación LuminosaRESUMEN
TRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals and heat allosterically gate TRPV1. Molecular determinants of TRPV1 activation by capsaicin, allicin, acid, ammonia and voltage have been identified. However, the structures and mechanisms mediating TRPV1's pronounced temperature sensitivity remain unclear. Recent studies of the related channel TRPV3 identified residues in the pore region that are required for heat activation. We used both random and targeted mutagenesis screens of rat TRPV1 and identified point mutations in the outer pore region that specifically impair temperature activation. Single-channel analysis indicated that TRPV1 mutations disrupted heat sensitivity by ablating long channel openings, which are part of the temperature-gating pathway. We propose that sequential occupancy of short and long open states on activation provides a mechanism for enhancing temperature sensitivity. Our results suggest that the outer pore is important for the heat sensitivity of thermoTRPs.