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

Neurodegenerative disorders are associated with widespread disruption to brain activity and brain rhythms. Some disorders are linked to dysfunction of the membrane-associated protein Tau. Here, we ask how brain rhythms are affected in rTg4510 mouse model of tauopathy, at an early stage of tauopathy (5 months), and at a more advanced stage (8 months). We measured brain rhythms in primary visual cortex in presence or absence of visual stimulation, while monitoring pupil diameter and locomotion to establish behavioral state. At 5 months, we found increased low-frequency rhythms during resting state in tauopathic animals, associated with periods of abnormally increased neural synchronization. At 8 months, this increase in low-frequency rhythms was accompanied by a reduction of power in the gamma range. Our results therefore show that slower rhythms are impaired earlier than gamma rhythms in this model of tauopathy, and suggest that electrophysiological measurements can track the progression of tauopathic neurodegeneration.

Plasticity in visual cortex is disrupted in a mouse model of tauopathy.

Alzheimer's disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer's disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tauopathy on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of tauopathy (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy. This simple measure of plasticity may help understand how tauopathy disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.

Creating and controlling visual environments using BonVision.

Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices.