RESUMEN
Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔVm ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina. Inner and outer retinal inhibition to Mbs was blocked with bath applied picrotoxin (PTX) and NBQX, respectively. Then, control and pharmacologically modified light responses were injected into axotomized Mb terminals as command potentials to induce voltage-gated Ca2+ influx (QCa ) and consequent glutamate release. Stimulus-evoked glutamate release was quantified by the increase in membrane capacitance (ΔCm ). Increasing depolarization of Mb terminals upon removal of inner and outer retinal inhibition enhanced the ΔVm /QCa ratio equally at a given light intensity and inhibition did not alter the overall relation between QCa and ΔCm . However, relative to control, light responses recorded in the presence of PTX and PTX + NBQX increased ΔCm unevenly across different stimulus intensities: at dim stimulus intensities predominantly the inner retinal GABAergic inhibition controlled release from Mbs, whereas the inner and outer retinal inhibition affected release equally in response to bright stimuli. Furthermore, our results suggest that non-linear relationship between QCa and glutamate release can influence the efficacy of inner and outer retinal inhibitory pathways to mediate Mb output at different light intensities.
Asunto(s)
Ácido Glutámico/metabolismo , Luz , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Red Nerviosa/fisiología , Inhibición Neural/fisiología , Células Bipolares de la Retina/fisiología , Células Bipolares de la Retina/efectos de la radiación , Animales , Biofisica , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Antagonistas del GABA/farmacología , Carpa Dorada , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Red Nerviosa/efectos de los fármacos , Red Nerviosa/efectos de la radiación , Inhibición Neural/efectos de los fármacos , Inhibición Neural/efectos de la radiación , Técnicas de Placa-Clamp , Picrotoxina/farmacología , Quinoxalinas/farmacología , Retina/citología , Células Bipolares de la Retina/efectos de los fármacosRESUMEN
Most retinal bipolar cells (BCs) transmit visual input from photoreceptors to ganglion cells using graded potentials, but some also generate calcium or sodium spikes. Sodium spikes are thought to increase temporal precision of light-evoked BC signaling; however, the role of calcium spikes in BCs is not fully understood. Here we studied how calcium spikes and graded responses mediate neurotransmitter release from Mb-type BCs, known to produce both. In dark-adapted goldfish retinal slices, light induced spikes in 40% of the axon terminals of intact Mbs; in the rest, light generated graded responses. These light-evoked membrane potentials were used to depolarize axotomized Mb terminals where depolarization-evoked calcium current (ICa) and consequent exocytosis-associated membrane capacitance increases (ΔCm) could be precisely measured. When evoked by identical dim light intensities, spiking responses transferred more calcium (Q(Ca)) and triggered larger exocytosis with higher efficiency (ΔCm/Q(Ca)) than graded potentials. Q(Ca) was translated into exocytosis linearly when transferred with spikes and supralinearly when transferred with graded responses. At the Mb output (ΔCm), spiking responses coded light intensity with numbers and amplitude whereas graded responses coded with amplitude, duration, and steepness. Importantly, spiking responses saturated exocytosis within scotopic range but graded potentials did not. We propose that calcium spikes in Mbs increase signal input-output ratio by boosting Mb glutamate release at threshold intensities. Therefore, spiking Mb responses are suitable to transfer low-light-intensity signals to ganglion cells with higher gain, whereas graded potentials signal for light over a wider range of intensities at the Mb output.
Asunto(s)
Señalización del Calcio/fisiología , Ácido Glutámico/metabolismo , Células Bipolares de la Retina/fisiología , Umbral Sensorial/fisiología , Visión Ocular/fisiología , Animales , Calcio/metabolismo , Capacidad Eléctrica , Exocitosis/fisiología , Carpa Dorada , Modelos Lineales , Potenciales de la Membrana/fisiología , Técnicas de Placa-Clamp , Estimulación Luminosa , Terminales Presinápticos/fisiología , Factores de Tiempo , Técnicas de Cultivo de TejidosRESUMEN
Direction-selective ganglion cells (DSGCs) respond selectively to motion toward a "preferred" direction, but much less to motion toward the opposite "null" direction. Directional signals in the DSGC depend on GABAergic inhibition and are observed over a wide range of speeds, which precludes motion detection based on a fixed temporal correlation. A voltage-clamp analysis, using narrow bar stimuli similar in width to the receptive field center, demonstrated that inhibition to DSGCs saturates rapidly above a threshold contrast. However, for wide bar stimuli that activate both the center and surround, inhibition depends more linearly on contrast. Excitation for both wide and narrow bars was also more linear. We propose that positive feedback, likely within the starburst amacrine cell or its network, produces steep saturation of inhibition at relatively low contrast. This mechanism renders GABA release essentially contrast and speed invariant, which enhances directional signals for small objects and thereby increases the signal-to-noise ratio for direction-selective signals in the spike train over a wide range of stimulus conditions. The steep saturation of inhibition confers to a neuron immunity to noise in its spike train, because when inhibition is strong no spikes are initiated.
Asunto(s)
Inhibición Neural/fisiología , Células Ganglionares de la Retina/fisiología , Visión Ocular/fisiología , Acetilcolina/metabolismo , Potenciales de Acción , Células Amacrinas/fisiología , Animales , Retroalimentación Fisiológica/fisiología , Ácido Glutámico/metabolismo , Cobayas , Movimiento (Física) , Técnicas de Placa-Clamp , Estimulación Luminosa/métodos , Conejos , Técnicas de Cultivo de Tejidos , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a "weighted potentiation" that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials. The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO-dependent ICa modulation was cGMP independent but could be blocked by N-ethylmaleimide (NEM), indicating that NO acted via an S-nitrosylation mechanism. Importantly, the NO action resulted in a weighted potentiation of Mb output in response to small (≤-30 mV) depolarizations. Coincidentally, light flashes with intensity ≥ 2.4 × 10(8) photons/cm(2)/s lowered the latency of scotopic (≤ 2.4 × 10(8) photons/cm(2)/s) light-evoked calcium spikes in Mb axon terminals in an NEM-sensitive manner, but light responses above cone threshold (≥ 3.5 × 10(9) photons/cm(2)/s) were unaltered. Under bright scotopic/mesopic conditions, this novel form of Mb output potentiation selectively amplifies dim retinal inputs at Mb â ganglion cell synapses. We propose that this process might counteract decreases in retinal sensitivity during light adaptation by preventing the loss of visual information carried by dim scotopic signals.
Asunto(s)
Carpa Dorada/fisiología , Plasticidad Neuronal/fisiología , Óxido Nítrico/fisiología , Compuestos Nitrosos/metabolismo , Células Bipolares de la Retina/fisiología , Algoritmos , Animales , Axotomía , Canales de Calcio Tipo L/fisiología , Señalización del Calcio/fisiología , GMP Cíclico/fisiología , Interpretación Estadística de Datos , Fenómenos Electrofisiológicos , Etilmaleimida/farmacología , Ácido Glutámico/fisiología , Técnicas In Vitro , Luz , Técnicas de Placa-Clamp , Estimulación Luminosa , Canales de Potasio con Entrada de Voltaje/fisiología , Retina/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiologíaRESUMEN
The outer retina removes the first-order correlation, the background light level, and thus more efficiently transmits contrast. This removal is accomplished by negative feedback from horizontal cell to photoreceptors. However, the optimal feedback gain to maximize the contrast sensitivity and spatial resolution is not known. The objective of this study was to determine, from the known structure of the outer retina, the synaptic gains that optimize the response to spatial and temporal contrast within natural images. We modeled the outer retina as a continuous 2D extension of the discrete 1D model of Yagi et al. (Proc Int Joint Conf Neural Netw 1: 787-789, 1989). We determined the spatio-temporal impulse response of the model using small-signal analysis, assuming that the stimulus did not perturb the resting state of the feedback system. In order to maximize the efficiency of the feedback system, we derived the relationships between time constants, space constants, and synaptic gains that give the fastest temporal adaptation and the highest spatial resolution of the photoreceptor input to bipolar cells. We found that feedback which directly modulated photoreceptor calcium channel activation, as opposed to changing photoreceptor voltage, provides faster adaptation to light onset and higher spatial resolution. The optimal solution suggests that the feedback gain from horizontal cells to photoreceptors should be approximately 0.5. The model can be extended to retinas that have two or more horizontal cell networks with different space constants. The theoretical predictions closely match experimental observations of outer retinal function.
Asunto(s)
Sensibilidad de Contraste/fisiología , Mamíferos/fisiología , Células Fotorreceptoras de Vertebrados/fisiología , Retina/fisiología , Células Horizontales de la Retina/fisiología , Animales , HumanosRESUMEN
Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for µ-opioid receptors (MORs) in both mouse and rat. In the rat retina, application of the MOR-selective agonist DAMGO attenuated light-evoked firing ipRGCs in a dose-dependent manner (IC50â¯<â¯40â¯nM), and this effect was reversed or prevented by co-application of the MOR-selective antagonists CTOP or CTAP. Recordings from solitary ipRGCs, enzymatically dissociated from retinas obtained from melanopsin-driven fluorescent reporter mice, confirmed that DAMGO exerts its effect directly through MORs expressed by ipRGCs. Reduced ipRGC excitability occurred via modulation of voltage-gated potassium and calcium currents. These findings suggest a potential new role for endogenous opioids in the mammalian retina and identify a novel site of action-MORs on ipRGCs-through which opioids might exert effects on reflexive responses to environmental light.