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The laboratory mouse has provided tremendous insight to the underpinnings of mammalian central nervous system physiology. In recent years, it has become possible to image single neurons, glia and vascular cells in vivo by using head-fixed preparations combined with cranial windows to study local networks of activity in the living brain. Such approaches have also succeeded without the use of general anesthesia providing insights to the natural behaviors of the central nervous system. However, the same has not yet been developed for the eye, which is constantly in motion. Here we characterize a novel head-fixed preparation that enables high-resolution adaptive optics retinal imaging at the single-cell level in awake-behaving mice. We reveal three new functional attributes of the normal eye that are overlooked by anesthesia: 1) High-frequency, low-amplitude eye motion of the mouse that is only present in the awake state 2) Single-cell blood flow in the mouse retina is reduced under anesthesia and 3) Mouse retinae thicken in response to ketamine/xylazine anesthesia. Here we show key benefits of the awake-behaving preparation that enables study of retinal physiology without anesthesia to study the normal retinal physiology in the mouse.

 

Neural codes for sensory inputs have been hypothesized to reside in a broader space defined by ongoing patterns of spontaneous activity. To understand the structure of this spontaneous activity in the olfactory system, we performed high-density recordings of neural populations in the main olfactory bulb of awake mice. We observed changes in pairwise correlations of spontaneous activity between mitral and tufted (M/T) cells when animals were running, which resulted in an increase in the entropy of the population. Surprisingly, pairwise maximum entropy models that described the population activity using only assumptions about the firing rates and correlations of neurons were better at predicting the global structure of activity when animals were stationary as compared to when they were running, implying that higher order (3rd, 4th order) interactions governed population activity during locomotion. Taken together, we found that locomotion alters the functional interactions that shape spontaneous population activity at the earliest stages of olfactory processing, one synapse away from the sensory receptors in the nasal epithelium. These data suggest that the coding space available for sensory representations responds adaptively to the animal’s behavioral state. NEW & NOTEWORTHY The organization and structure of spontaneous population activity in the olfactory system places constraints of how odor information is represented. Using high-density electrophysiological recordings of mitral and tufted cells, we found that running increases the dimensionality of spontaneous activity, implicating higher order interactions among neurons during locomotion. Behavior, thus, flexibly alters neuronal activity at the earliest stages of sensory processing. 

While the link between amyloid β (Aβ) accumulation and synaptic degradation in Alzheimer’s disease (AD) is known, the consequences of this pathology on population coding remain unknown. We found that the entropy, a measure of the diversity of network firing patterns, was lower in the dorsal CA1 region in the APP/PS1 mouse model of Aβ pathology, relative to controls, thereby reducing the population’s coding capacity. Our results reveal a network level signature of the deficits Aβ accumulation causes to the computations performed by neural circuits.

 

Sex differences in running behaviors between female and male mice occur naturally in the wild. Recent experiments using head‐fixed mice on a voluntary running wheel have exploited analogous locomotor activity to gain insight into the neural underpinnings of a number of behaviors ranging from spatial navigation to decision‐making. It is however largely unknown if sex differences exist between females and males in a head‐fixed experimental paradigm. To address this, we characterized locomotor activity in head‐fixed female and male C57BL/6J mice on a voluntary running wheel. First, we found that over the initial 7‐day period, on average, animals increased both the velocity and the time spent running. Furthermore, we found that female mice habituated to running forward over the initial 2 days of encountering the wheel, while male mice took up to 4 days to habituate to running forward. Taken together, we characterized features of a sexually divergent behavior in head‐fixed running that should be considered in experiments employing female and male mice.