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Neural modulation and activity dependent changes in the visual system
2S4-1
Study on electrically induced responses in visual cortex for visual prosthetics
Yagi Tetsuya
the Graduate School of Engineering, Osaka University

Electrical stimulus applied to the extracellular space of visual cortex evokes a spot-like light percept called phosphen, which provoked the research of cortical prosthetics for blind patients. Previous clinical experiments on human volunteer patients revealed that the evoked phosphens changed their appearance depending on temporal patterns of electrical stimulation. However, relation between the stimulus parameters and the evoked percepts is not well understood. To evaluate percepts evoked by cortical prosthetics, spatiotemporal properties of electrically induced cortical activities were studied in terms of stimulation parameters to reconstruct physiologically feasible phosphen patterns. We conducted a voltage-sensitive dye imaging of cortical responses induced by current stimuli applied to V1 in rodents, which allowed one to study how the induced responses propagate in V1 and to higher order cortical areas. All experiments were approved by the Institutional Animal Care and Use Committee of the Graduate School of Engineering, Osaka University. A single current pulse(>10μA)with biphasic waveform applied with a metal electrode(ME13213, MicroPrpbes)induced responses which resembled the PSPs observed in previous electrical recordings on single cells in mammals. The threshold and the half activating intensity was 5-10μA and around 40μA, respectively. The induced response propagated laterally in V1 via a poly-synaptic transmission. For a low current intensity(<10μA), the excitatory response to a repetitive stimulation was cumulative for several hundreds of ms. The response to each stimulus pulse showed synaptic depression, that was more prominent at higher stimulus intensities(>20μA)and gradually diminished as the repetitive stimulation continued for >1s. The response to the repetitive stimuli declined more rapidly in V2 than in V1, indicated the signal transmission from V1 to V2 is not sustained. According to the present experiments and previous clinical experiments, physiologically feasible phosphen patterns were reconstructed on a head mount display and presented to volunteer subjects to evaluate the visual percepts evoked by cortical prosthetics. The feasible prosthesis were designed and a prototype was implemented for animal experiments.
2S4-2
Monoaminergic/cholinergic modulation of neuronal visual information processing and behavioral contrast detectability.
Shimegi Satoshi
Graduate School of Medicine, Osaka University

Our brain is regarded as a computer processor, but there is a crucial difference between them. The brain can dynamically change the input-output relationship depending on physiological states and behavioral contexts to optimize the information processing while the computer processor can’t. Monoaminergic/cholinergic transmitters such as serotonin(5-HT), noradrenaline(NA), and acetylcholine(ACh)play central roles in the state/context-dependent modulation of brain functions. In this presentation, I’ll talk about how those transmitters modulate visual information processing at the single neuron level and improve behavioral visual ability. Using drifting sinusoidal grating stimuli with various contrast, a contrast-response function(input-output relationship)was estimated for individual V1 neurons of anesthetized monkeys, and the effects of micro-iontophoretic administration of agonists/antagonists of those receptors on the contrast-response functions were tested. The effects was complex but reasonable. For example, each activation of 5-HT1B and 5-HT2A receptors exerted both suppressive and facilitative effects, depending on the firing rate of the recorded neurons. The detailed analysis suggested that 5-HT1B receptors enhance the signal-to-noise(S/N)ratio of visual responses by suppressing spontaneous activity(noise)and facilitating visual response(signal), and 5-HT2A act as a gain controller by enhancing weak response and suppressing excessive response. ACh also enhanced S/N ratio and modulated the contrast-response function mainly in a manner of response gain control for V1 of monkeys and rats. To examine whether the neuronal modulation contributes to visual ability, we performed behavioral measurements of contrast sensitivity in freely moving rats, and tested the effects of the systemic injection of various drugs on the contrast sensitivity. We found that contrast detectability was improved by donepezil, a cholinesterase inhibitor, suggesting that ACh endogenously released in cognitive behavior controls the contrast detectability by modulating cortical visual information processing. Thus, monoaminergic/cholinergic systems seem to control the fine and elaborated functions of the primate visual system to meet the purposes of behavioral context.
2S4-3
Ocular dominance plasticity regulated by Otx2-inducible molecules
Sugiyama Sayaka
Lab of Neuronal Dev., Grad Sch. Med. Dent. Sci., Niigata Univ.

Understanding molecular mechanisms of experience-dependent plasticity is a subject of intense investigation. For example, inputs from the two eyes first converge in the primary visual cortex, where competitive interactions determine which eye will eventually dominate both functionally and anatomically. It is widely believed that distinct GABAergic circuits drive the critical period of ocular dominance plasticity. Our previous report showed that experience-dependent transfer of Otx2 homeoprotein into parvalbumin(PV)-cells activates this sensitive period. Otx2 deletion results in reduction of mature PV-cells enwrapped by chondroitin sulfate glycosaminoglycans and in disruption of plasticity. This homeoprotein may promote a downstream cascade for plasticity, however its target genes remain obscure. Recently, we found that Otx2 induced chondroitin sulfate surrounding PV-cells and that chondroitin sulfate further promoted Otx2 accumulation. A positive feedback loop between Otx2 and chondroitin sulfate regulates the onset and offset of plasticity. Moreover, Otx2 also induces an actin-binding protein within PV-cells that modulates plasticity. Thus, our results indicate that ocular dominance plasticity is elicited through a well-balanced cooperation of Otx2-inducible molecules inside and outside PV-cells.
2S4-4
Modulation of visual behavior by central thalamic deep brain stimulation
Purpura Keith1,Baker Jonathan1,Ryou Jae-Wook1,Wei Xuefeng2,Butson Christopher R.3,Schiff Nicholas D.1
1Brain & Mind Research Institute, Weill Cornell Medical College,2The College of New Jersey,3Dept. of Biomedical Engineering, University of Utah

The central thalamus is believed to play an important role in enabling the cerebral cortex to produce behavior and mental states including consciousness. Following the successful use of deep brain stimulation(DBS)to treat movement disorders, it was hypothesized that targeting DBS to the central thalamus of patients with disorders of consciousness(DOC)could help restore cognitive function by modulating activity in the anterior forebrain. The goal of the study described here is to better understand the mechanisms of DBS in the central thalamus and to test methods for improving its effectiveness. We carried out experiments in two normal macaques to test the effects of DBS on visual behavior. Both monkeys were implanted with multiple DBS electrodes in their central thalami. One monkey was trained to perform three tasks:1)a sustained visual attention reaction time task;2)a memory-guided saccade task;3)a visual pattern categorization task. The second monkey was trained on Task 1. Large-scale brain activity was recorded with an array of electrocorticography(EcoG)leads implanted in the skull and with a chronically-implanted array of microelectrodes in the frontal lobe and striatum. High-frequency periodic DBS was turned on and off throughout the behavioral sessions to determine the effect of DBS on task performance and on brain activity. We found that DBS in the central thalamus profoundly modified visual behavior and brain-wide electrical activity. Specific DBS frequencies, when matched with one particular electrode configuration of current injection, were most effective at sustaining performance over many trials, decreasing reaction times and improving pattern categorization. In addition, this method of stimulation also shifted the power spectrum in the EcoG and microelectrode local field potentials:slow rhythmic brain activity decreased and fast rhythmic brain activity increased compared to when DBS was turned off. Our results demonstrate that central thalamic DBS can modulate innate patterns of brain activity and visual behavior, and may provide a means for normalizing impaired cognitive capacity.