Abstract
Retinal degeneration (RD) is defined as deterioration of the retina with the consequent loss of retinal cells, especially photoreceptors. This condition causes progressive vision impairment or a total loss of sight in some cases. Although no cure has yet been identified for diseases related to RD, many efforts have been made to treat this condition, including gene therapy, transplantation, and the use of visual prostheses. In particular, the latter aims to restore a patient’s vision using artificial devices. Although many types of visual prostheses exist, all basically depend on intact structures along the patient’s visual pathway. Therefore, the morphology, physiological properties and, most importantly, the functional performance of the remaining intact structures are crucial factors in the success of visual prosthetic treatment and must be investigated.To date, the early stage of visual system, and especially the retina, has been well investigated. By contrast, relatively few studies have addressed the middle and late stages of the visual pathway. For instance, although previous works have characterized the receptive fields of neurons in the primary visual cortex (V1) of an RD model, the functional performance of these fields remained unclear. Accordingly, the present study aimed to investigate electrophysiological and functional changes in the V1 of an RD model. Specifically, this study examined the complexity of spontaneous activities and the transmission of information regarding responsive activities in addition to the basic electrophysiological properties. Notably, both artificial and natural visual stimulation were used to characterize the responsive activities.
Wild-type (WT) and RD model rats were used experimentally to study spontaneous neural activity in the V1. We recorded the spontaneous extracellular neural activities in the V1 of both groups and subsequently analyzed the firing rate, interspike interval (ISI) and Lempel-Ziv (LZ) complexity of these activities. Compared with the control group, neurons in the primary visual cortex of the RD model fired more frequently. In addition, the RD model exhibited a decrease in the LZ complexity of spontaneous neural firing. These results imply that RD may not only affect the retina itself, but also the primary visual cortex and may lead to an imbalance of the inhibition-excitation system and a decrease in the rate at which new spontaneous activity patterns (or neural encoding potential) arise.
Next, the neural responses in the V1 were recorded extracellularly while the subjects received visual light stimuli at varied intensities to investigate responsive neural activities under an artificial flicker stimulus in the primary visual cortex. First, the firing rate and its relationship with the light intensity were compared between the WT and RD groups. Second, mutual information (MI) between the visual stimulus and neural response was determined for every isolated unit and used to quantify the amount and efficiency of information transmission in the V1 of both the WT and RD groups. Third, the local field potential (LFP) signal was also characterized and its power was used to compute the MI, which in turn was used to further evaluate the functional change in information transmission in the RD model. The results from the analysis of spiking activity demonstrated relative decreases in the firing rate, information amount and efficiency in the RD group relative to the control group. However, the analysis of LFP activity revealed that the RD model and WT group exhibited similar performances with regard to information transmission. These findings implied that although the early stage of the visual system was impaired in RD rats, the latter part of the visual system, V1, could still capture the information of visual stimuli, especially at the population level.
To characterize responsive neural activities in the primary visual cortex of RD models in the context of a natural image stimulus, neural responses in the V1 were recorded extracellularly during exposure to a movie stimulus. First, we compared the relationship between the firing rate and light intensity in both the WT and RD groups. Second, we determined MI between the visual stimulus and the spiking responses for every isolated neuron to quantify the amount and efficiency of information transmission in the V1 of the experimental and control groups. Third, we characterized the LFP signal and investigated different measures, including amplitude, phase, instantaneous frequency and power. Fourth, we calculated the information measures using power to further evaluate functional changes in the V1 of the RD model regarding information transmission. The results from the analysis of spiking activities indicated a lack of a significant difference between the WT and RD groups in terms of the firing rate, whereas the MI in the RD group decreased significantly relative to the control group. In the context of LFP activity, the two groups exhibited a similar performance with respect to information transmission. These findings implied that although the early stage of the visual system was impaired in RD rats, the later part of the visual system, V1, could still capture information of visual stimuli, especially in low-frequency bands and at a population level. Taken together with the results from flicker-evoked activity analyses, these findings prove that the V1 stage in the visual pathway could be used to restore visual ability (e.g., via visual prostheses).
| Date of Award | 3 Sept 2018 |
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| Original language | English |
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| Supervisor | L H Leanne CHAN (Supervisor) |