Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.

Astrocytes: integrators of arousal state and sensory context.

The integration of external information with the internal state of the body is central to the survival of virtually every multicellular organism. However, a complete picture of the mechanisms that govern this process is lacking. In this opinion article, we synthesize evidence demonstrating that astrocytes sense the momentary arousal state - through neuromodulator release - as well as the sensory inputs - through local synaptic activity - and respond to them with changes in calcium (Ca2+) signaling. We hypothesize that astrocytes integrate sensory signals with the internal state and that this process is necessary to secure optimal behavior. Finally, we argue that dysfunctional astrocytic Ca2+ signaling could be an underlying factor in disorders characterized by disrupted sensory processing.

More than meets the eye: The metabolic state of the body shapes visual sensations.

How body metabolism impacts sensory processing in the brain remains unresolved. In a recent study in Neuron, Padamsey et al. (2021) revealed that when the body is food restricted for several weeks, neurons in the visual cortex reduce their energy consumption at the cost of response selectivity and visual performance.

The elusive varicose astrocytes.

The evolutionary pattern of different astrocyte types across animal species remains unresolved. In a recent study, Falcone and colleagues revealed that varicose projection astrocytes, a rare form of astrocyte characterized by long varicosities-containing processes, are exclusively found in hominoid brains while being absent from other primate brains.

Versatile treadmill system for measuring locomotion and neural activity in head-fixed mice.

Here, we present a protocol for using a versatile treadmill system to measure locomotion and neural activity at high temporal resolution in head-fixed mice. We first describe the assembly of the treadmill system. We then detail surgical implantation of the headplate on the mouse skull, followed by habituation of mice to locomotion on the treadmill system. The system is compact, movable, and simple to synchronize with other data streams, making it ideal for monitoring brain activity in diverse behavioral frameworks. For complete details on the use and execution of this protocol, please refer to Rasmussen et al. (2019).

EyeLoop: An Open-Source System for High-Speed, Closed-Loop Eye-Tracking.

Eye-trackers are widely used to study nervous system dynamics and neuropathology. Despite this broad utility, eye-tracking remains expensive, hardware-intensive, and proprietary, limiting its use to high-resource facilities. It also does not easily allow for real-time analysis and closed-loop design to link eye movements to neural activity. To address these issues, we developed an open-source eye-tracker - EyeLoop - that uses a highly efficient vectorized pupil detection method to provide uninterrupted tracking and fast online analysis with high accuracy on par with popular eye tracking modules, such as DeepLabCut. This Python-based software easily integrates custom functions using code modules, tracks a multitude of eyes, including in rodents, humans, and non-human primates, and operates at more than 1,000 frames per second on consumer-grade hardware. In this paper, we demonstrate EyeLoop's utility in an open-loop experiment and in biomedical disease identification, two common applications of eye-tracking. With a remarkably low cost and minimum setup steps, EyeLoop makes high-speed eye-tracking widely accessible.

Binocular integration of retinal motion information underlies optic flow processing by the cortex.

Locomotion creates various patterns of optic flow on the retina, which provide the observer with information about their movement relative to the environment. However, it is unclear how these optic flow patterns are encoded by the cortex. Here, we use two-photon calcium imaging in awake mice to systematically map monocular and binocular responses to horizontal motion in four areas of the visual cortex. We find that neurons selective to translational or rotational optic flow are abundant in higher visual areas, whereas neurons suppressed by binocular motion are more common in the primary visual cortex. Disruption of retinal direction selectivity in Frmd7 mutant mice reduces the number of translation-selective neurons in the primary visual cortex and translation- and rotation-selective neurons as well as binocular direction-selective neurons in the rostrolateral and anterior visual cortex, blurring the functional distinction between primary and higher visual areas. Thus, optic flow representations in specific areas of the visual cortex rely on binocular integration of motion information from the retina.