A dynamic sequence of visual processing initiated by gaze shifts.

Animals move their head and eyes as they explore the visual scene. Neural correlates of these movements have been found in rodent primary visual cortex (V1), but their sources and computational roles are unclear. We addressed this by combining head and eye movement measurements with neural recordings in freely moving mice. V1 neurons responded primarily to gaze shifts, where head movements are accompanied by saccadic eye movements, rather than to head movements where compensatory eye movements stabilize gaze. A variety of activity patterns followed gaze shifts and together these formed a temporal sequence that was absent in darkness. Gaze-shift responses resembled those evoked by sequentially flashed stimuli, suggesting a large component corresponds to onset of new visual input. Notably, neurons responded in a sequence that matches their spatial frequency bias, consistent with coarse-to-fine processing. Recordings in freely gazing marmosets revealed a similar sequence following saccades, also aligned to spatial frequency preference. Our results demonstrate that active vision in both mice and marmosets consists of a dynamic temporal sequence of neural activity associated with visual sampling.

Joint coding of visual input and eye/head position in V1 of freely moving mice.

Visual input during natural behavior is highly dependent on movements of the eyes and head, but how information about eye and head position is integrated with visual processing during free movement is unknown, as visual physiology is generally performed under head fixation. To address this, we performed single-unit electrophysiology in V1 of freely moving mice while simultaneously measuring the mouse's eye position, head orientation, and the visual scene from the mouse's perspective. From these measures, we mapped spatiotemporal receptive fields during free movement based on the gaze-corrected visual input. Furthermore, we found a significant fraction of neurons tuned for eye and head position, and these signals were integrated with visual responses through a multiplicative mechanism in the majority of modulated neurons. These results provide new insight into coding in the mouse V1 and, more generally, provide a paradigm for investigating visual physiology under natural conditions, including active sensing and ethological behavior.

Distance estimation from monocular cues in an ethological visuomotor task.

In natural contexts, sensory processing and motor output are closely coupled, which is reflected in the fact that many brain areas contain both sensory and movement signals. However, standard reductionist paradigms decouple sensory decisions from their natural motor consequences, and head-fixation prevents the natural sensory consequences of self-motion. In particular, movement through the environment provides a number of depth cues beyond stereo vision that are poorly understood. To study the integration of visual processing and motor output in a naturalistic task, we investigated distance estimation in freely moving mice. We found that mice use vision to accurately jump across a variable gap, thus directly coupling a visual computation to its corresponding ethological motor output. Monocular eyelid suture did not affect gap jumping success, thus mice can use cues that do not depend on binocular disparity and stereo vision. Under monocular conditions, mice altered their head positioning and performed more vertical head movements, consistent with a shift from using stereopsis to other monocular cues, such as motion or position parallax. Finally, optogenetic suppression of primary visual cortex impaired task performance under both binocular and monocular conditions when optical fiber placement was localized to binocular or monocular zone V1, respectively. Together, these results show that mice can use monocular cues, relying on visual cortex, to accurately judge distance. Furthermore, this behavioral paradigm provides a foundation for studying how neural circuits convert sensory information into ethological motor output.

Targeted Assessment of Enlargement of the Perivascular Space in Alzheimer's Disease and Vascular Dementia Subtypes Implicates Astroglial Involvement Specific to Alzheimer's Disease.

Waste clearance from the brain parenchyma occurs along perivascular pathways. Enlargement of the perivascular space (ePVS) is associated with pathologic features of Alzheimer's disease (AD), although the mechanisms and implications of this dilation are unclear. Fluid exchange along the cerebral vasculature is dependent on the perivascular astrocytic water channel aquaporin-4 (AQP4) and loss of perivascular AQP4 localization is found in AD. We directly measured ePVS in postmortem samples of pathologically characterized tissue from participants who were cognitively intact or had AD or mixed dementia (vascular lesions with AD). We found that both AD and mixed dementia groups had significantly increased ePVS compared to cognitively intact subjects. In addition, we found increased global AQP4 expression of the AD group over both control and mixed dementia groups and a qualitative reduction in perivascular localization of AQP4 in the AD group. Among these cases, increasing ePVS burden was associated with the presence of tau and amyloid-ß pathology. These findings are consistent with the existing evidence of ePVS in AD and provide novel information regarding differences in AD and vascular dementia and the potential role of astroglial pathology in ePVS.