Synergistic roles of GABAA receptors and SK channels in regulating thalamocortical oscillations.

Rhythmic oscillations throughout the cortex are observed during physiological and pathological states of the brain. The thalamus generates sleep spindle oscillations and spike-wave discharges characteristic of absence epilepsy. Much has been learned regarding the mechanisms underlying these oscillations from in vitro brain slice preparations. One widely used model to understand the epileptiform oscillations underlying absence epilepsy involves application of bicuculline methiodide (BMI) to brain slices containing the thalamus. BMI is a well-known GABAA receptor blocker that has previously been discovered to also block small-conductance, calcium-activated potassium (SK) channels. Here we report that the robust epileptiform oscillations observed during BMI application rely synergistically on both GABAA receptor and SK channel antagonism. Neither application of picrotoxin, a selective GABAA receptor antagonist, nor application of apamin, a selective SK channel antagonist, alone yielded the highly synchronized, long-lasting oscillations comparable to those observed during BMI application. However, partial blockade of SK channels by subnanomolar concentrations of apamin combined with picrotoxin sufficiently replicated BMI oscillations. We found that, at the cellular level, apamin enhanced the intrinsic excitability of reticular nucleus (RT) neurons but had no effect on relay neurons. This work suggests that regulation of RT excitability by SK channels can influence the excitability of thalamocortical networks and may illuminate possible pharmacological treatments for absence epilepsy. Finally, our results suggest that changes in the intrinsic properties of individual neurons and changes at the circuit level can robustly modulate these oscillations.

Image processing for a high-resolution optoelectronic retinal prosthesis.

In an effort to restore visual perception in retinal diseases such as age-related macular degeneration or retinitis pigmentosa, a design was recently presented for a high-resolution optoelectronic retinal prosthesis having thousands of electrodes. This system requires real-time image processing fast enough to convert a video stream of images into electrical stimulus patterns that can be properly interpreted by the brain. Here, we present image-processing and tracking algorithms for a subretinal implant designed to stimulate the second neuron in the visual pathway, bypassing the degenerated first synaptic layer. For this task, we have developed and implemented: 1) A tracking algorithm that determines the implant's position in each frame. 2) Image cropping outside of the implant boundaries. 3) A geometrical transformation that distorts the image appropriate to the geometry of the fovea. 4) Spatio-temporal image filtering to reproduce the visual processing normally occurring in photoceptors and at the photoreceptor-bipolar cell synapse. 5) Conversion of the filtered visual information into a pattern of electrical current. Methods to accelerate real-time transformations include the exploitation of data redundancy in the time domain, and the use of precomputed lookup tables that are adjustable to retinal physiology and allow flexible control of stimulation parameters. A software implementation of these algorithms processes natural visual scenes with sufficient speed for real-time operation. This computationally efficient algorithm resembles, in some aspects, biological strategies of efficient coding in the retina and could provide a refresh rate higher than fifty frames per second on our system.

Subperiosteal orbital hemorrhage as initial manifestation of Christmas disease (factor IX deficiency).

PURPOSE: To report a case of subperiosteal orbital and subgaleal hemorrhage with optic nerve compromise in a patient with a factor IX deficiency. DESIGN: Interventional case report. METHODS: A 5-year-old male presented 10 days after mild trauma with progressive left-sided scalp swelling, proptosis, and visual loss. RESULTS: The patient had marked proptosis of the left eye, 20/200 visual acuity, and an afferent pupillary defect. Magnetic resonance imaging demonstrated a large subgaleal and left subperiosteal orbital hematoma. Quantitative assays of coagulation proteins identified a factor IX deficiency (Christmas disease). CONCLUSION: Delayed-onset subgaleal and subperiosteal orbital hematoma can rarely be an initial manifestation of Christmas disease.