Spiking Activity Of Ganglion Cells Research Articles

Retinal Pathway Origins of the Pattern Electroretinogram (PERG)

To determine retinal pathway origins of pattern electroretinogram (PERG) in macaque monkeys using pharmacologic dissections, uniform-field flashes, and PERG simulations. Transient (2 Hz, 4 reversals/s) and steady state (8.3 Hz, 16.6 reversals/s) PERGs and uniform-field ERGs were recorded before and after intravitreal injections of L-AP4 (not APB) (2-amino-4-phosphonobutyric acid, 1.6-2.0 mM), to prevent ON pathway responses; PDA (cis-2,3-piperidinedicarboxylic acid, 3.3-3.8 mM), to block activity of hyperpolarizing second- and all third-order retinal neurons; and TTX (tetrodotoxin, 6 μM), to block Na+-dependent spiking. PERGs were also recorded from macaques with advanced unilateral experimental glaucoma, and were simulated by averaging ON and OFF responses to uniform-field flashes. For 2-Hz stimulation, L-AP4 reduced both negative- and positive-going (N95 and P50) amplitudes in transient PERGs, and their counterparts, N2 and P1 in simulations, to half-amplitude. PDA eliminated N95 and N2, but increased P50 and P1 amplitudes, in that it enhanced b-waves. As previously reported, severe experimental glaucoma or TTX eliminated photopic negative responses, N95, and N2; glaucoma eliminated P50 and reduced P1 amplitude; TTX reduced P50 and hardly altered P1. For 8.3-Hz stimulation, L-AP4 eliminated the steady state PERG and reduced simulated PERG amplitude, whereas PDA enhanced both responses. TTX reduced PERG amplitude to less than half; simulations were less reduced. Blockade of all postreceptoral activity eliminated transient and steady state PERGs, but left small residual P1 in simulations. Transient PERG receives nearly equal amplitude contributions from ON and OFF pathways. N95 reflects spiking activity of ganglion cells; P50 reflects nonspiking activity as well. Steady state PERG, in contrast, reflects mainly spike-related ON pathway activity.

Restoration of Cone Vision in the CNGA3−/− Mouse Model of Congenital Complete Lack of Cone Photoreceptor Function

Congenital absence of cone photoreceptor function is associated with strongly impaired daylight vision and loss of color discrimination in human achromatopsia. Here, we introduce viral gene replacement therapy as a potential treatment for this disease in the CNGA3(-/-) mouse model. We show that such therapy can restore cone-specific visual processing in the central nervous system even if cone photoreceptors had been nonfunctional from birth. The restoration of cone vision was assessed at different stages along the visual pathway. Treated CNGA3(-/-) mice were able to generate cone photoreceptor responses and to transfer these signals to bipolar cells. In support, we found morphologically that treated cones expressed regular cyclic nucleotide-gated (CNG) channel complexes and opsins in outer segments, which previously they did not. Moreover, expression of CNGA3 normalized cyclic guanosine monophosphate (cGMP) levels in cones, delayed cone cell death and reduced the inflammatory response of Müller glia cells that is typical of retinal degenerations. Furthermore, ganglion cells from treated, but not from untreated, CNGA3(-/-) mice displayed cone-driven, light-evoked, spiking activity, indicating that signals generated in the outer retina are transmitted to the brain. Finally, we demonstrate that this newly acquired sensory information was translated into cone-mediated, vision-guided behavior.

Electrophysiological effects of tachykinin analogues on ganglion cell activity in cyprinid fish retina

Electrical spike activity of ganglion cells has been recorded extracellularly in the teleost (roach) retina, and effects of a variety of tachykinins studied at a working concentration of 1 μM. Application of substance P mostly caused a slow and prolonged increase in background activity. In contrast, the response to carbachol was very brisk and short-lasting. Substance P and physalaemin predominantly induced an enhancement of ‘On’ and ‘Off’ components of light-evoked responses, whilst eledoisin and neurokinin A were mostly inhibitory. All effects were independent of chromatic and spatial aspects of the responses. Interestingly, in the presence of a tachykinin antagonist, ‘Spantide’ [D-Arg 1, D-Pro 2, D-Trp 7,9, Leu 11]SP, the profile of the effect of substance P reversed, inhibitory actions becoming much more common. Taken together, the results suggest that a tachykinin system utilising two subtypes of the receptor may be active in the roach retina and these may be involved in differential control of visual sensitivity.

Analysis of the horizontal cell contribution to the receptive field surround of ganglion cells in the rabbit retina.

1. The influence of horizontal cells on ganglion cells, the output neuron of the retina, was examined in an in vitro rabbit eyecup preparation. The extracellular spike activity of ganglion cells was monitored while pulsatile DC or sinusoidally modulated current was injected intracellularly into nearby horizontal cells. Interactions between the effects of light stimulation and horizontal cell current injections on ganglion cell responses were also examined. 2. Horizontal cells were found to contribute to the receptive field surround of ganglion cells. In particular, horizontal cells contributed to surround excitability and to surround antagonism of the centre light response. 3. Brisk, sluggish and direction-selective ganglion cells were all affected by current injections into horizontal cells. However, brisk ganglion cells responded to lower amplitude currents than did sluggish or direction-selective cells. 4. Horizontal cells with receptive fields that overlap those of ganglion cells were able to affect ganglion cell discharge. Moreover, the closer a horizontal cell was to the receptive field centre of a ganglion cell, the more effective were current injections in modulating ganglion cell discharge rate. The length constant of the horizontal cell contribution to the ganglion cell receptive field was approximately 200 microns. These results indicate that horizontal cells which are located within or outside of a ganglion cell's receptive field centre can influence that ganglion cell's activity. 5. The influence of horizontal cells on ganglion cell discharges was relatively weak at low temporal frequencies of sinusoidally modulated current. 6. Application of 2-amino-4-phosphonobutyrate (APB), a glutamate analogue, blocked the modulation of spike activity of on-centre ganglion cells that was induced by sinusoidally modulated current injected into nearby horizontal cells. The spike activity of off-centre ganglion cells was not blocked. 7. These findings suggest that horizontal cells contribute to the surround of ganglion cells and bipolar cells primarily through a feedback pathway onto cone photoreceptor cells.