Disrupted visual cortical plasticity in early neurodegeneration

Abstract

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.

The spatiotemporal organization of experience dictates hippocampal involvement in primary visual cortical plasticity

“…Thus, SRP might likewise involve spatiotemporal prediction. Consistent with this idea, SRP expression possesses emergent properties, manifesting not at the onset of a train of familiar visual stimuli but rather on subsequent phase reversals (37)(38)(39). If SRP were revealed to be strongly dependent on temporal characteristics of visual experience (as it is for spatial features (40)) this would challenge our interpretation that hippocampal lesions selectively disrupt sequential pattern completion.…”

The spatiotemporal organization of experience dictates hippocampal involvement in primary visual cortical plasticity

“…Consistent with this idea, SRP expression possesses emergent properties, manifesting not at the onset of a train of familiar visual stimuli but rather on subsequent phase reversals. [37][38][39] If SRP was revealed to be strongly dependent on temporal characteristics of visual experience (as it is for spatial features), 40 this would challenge our interpretation that hippocampal lesions selectively disrupt sequential pattern completion. To clarify whether SRP reflects familiarity with stimulus identity or anticipatory prediction of a temporal pattern, a cohort of neurotypical mice was exposed daily to a static grating stimulus at a fixed spatial orientation.…”

Altered low frequency brain rhythms precede changes in gamma power during tauopathy

“…A reduction in overall gamma power was observed at 8m, both in the presence and absence of any visual stimulation. Panels A to C are adapted from Papanikolaou et al (2021).…”

“…Movement speed was recorded using a rotary encoder; pupil size and position were measured via an infrared camera (DMK 22BUC03, ImagingSource; 30 Hz) focused on the left eye through a zoom lens (Computar MLH-10X Macro Zoom Lens), and extracted from these videos using custom routines in Bonsai (Lopes et al, 2015). Following habituation, animals were tested daily over 9 consecutive days just as described in Papanikolaou et al (2021). For the purpose of the current study, we only considered recordings made from day 2 to day 8 (7 days total).…”

“…The LFP and rotary wheel signals were sampled at 30kHz, and were synchronized with pupil measurements and visual stimulus via the signal of a photodiode (PDA25K2, Thorlabs, Inc., USA) that monitored timing pulses on a small corner of the monitor shielded from the animal. Portions of the same recordings were used to measure visually-evoked potentials reported elsewhere (Papanikolaou et al, 2021). All data have been reanalysed for the current purposes.…”