Full-field electroretinogram response to increment and decrement stimuli.

PURPOSE: The d-wave is typically elicited after the termination of an increment flash, but a decrement flash provides an alternative, and perhaps more appropriate, stimulus to elicit the d-wave. Here, we investigated the affects of stimulus polarity on the electroretinogram (ERG) response. METHODS: ERG responses elicited to increment and decrement flashes of varying intensity and duration from different background levels were measured from human participants to assess the b-wave and d-wave responses as a function of adaptation level and flash polarity. Response amplitudes were measured using standard metrics for waveform analysis. RESULTS: The amplitude of the b-wave is larger than the d-wave regardless of flash polarity when using different background levels which maximized the dynamic range of the two waveforms. However, when response amplitudes are measured from a common background, the d-wave elicited with decrement flash was larger than the b-wave elicited by an increment flash. This trend was evident across a range of background levels. The b-wave and d-wave become separate entities when flash duration reaches approximately 50 ms. Rapid-on and rapid-off sawtooth stimuli were also tested against increment and decrement step stimuli that were matched in mean luminance. These two stimulus types produced different amplitude b-wave and d-wave responses, suggesting asymmetric effects of the two stimulus types on the retinal response. CONCLUSIONS: We conclude that the response properties of the b-wave and d-wave are influenced by the duration, polarity and waveform of the stimulus, as well as the background from which the stimuli arise.

Apoptosis in oligodendrocytes is associated with axonal degeneration in P301L tau mice.

Transgenic mice overexpressing human tau with the P301L mutation develop neurofibrillary tangles, extensive gliosis, adult-onset motor abnormalities, and neuronal loss in affected brain regions. We investigated the mechanism of neuronal cell death in this model of tauopathy. There was no evidence of neuronal apoptosis at any age; however, a population of oligodendorocytes was immunopositive for TUNEL and activated caspase-3. EM confirmed that these oligodendrocytes were undergoing apoptosis. These data suggest that classical apoptosis is not a major mechanism of neuronal cell death associated with the tau dysfunction in this mouse model; however, prominent white matter pathology in the spinal cord suggests that axonal degeneration in dying neurons causes oligodendrocytes to undergo apoptosis. It is unknown if loss of oligodendrocytes either through apoptosis or through the formation of intracellular tau lesions further contributes to the neurodegeneration seen in these mice.