Behavioral Correlates in Sleeping Laboratory Mice with Widefield Imaging

Presenter(s): Ally Wimberly

Faculty Mentor(s): Paul Steffan & David McCormick

Poster 70

Session: Sciences

Pupillometry has effectively correlated pupil size with cortical states in awake mice. High amounts of brain activity have been associated with large pupil size whereas low amounts of brain activity associate with smaller pupil size in awake mice. The purpose of this project is to acquire widefield imaging on sleeping laboratory mice in order to gain a better understanding of mouse neuronal activity during sleep. I aim to find lower amounts of brain activity and small pupil size during non-REM sleep along with high amounts of brain activity with large pupil size during REM sleep. The widefield and pupil imaging will provide the opportunity to correlate certain neuronal activity with behaviors and other neuronal activity with deeper neural mechanisms happening during sleep. Some of the behavior correlates we will use are: movement of whiskers, paws, and fluctuation of the pupil size. Once the behavioral activity is excluded, the deeper neural mechanisms during sleep will be narrowed down and able to be focused on. Finding the deeper neural mechanisms will enable us to track neural circuits and networks involved during different stages of sleep in order to evolve a better profile of overall neuronal activity during sleep.

The Effect of Varying Reward Treatments on Performance and Learning Acquisition in Mice

Presenter(s): John Francis

Faculty Mentor(s): Paul Steffan & David McCormick

Poster 37

Session: Sciences

An animal’s ability to interpret and respond to environmental stimuli is highly variable, depending on factors such as the reward the animal receives for correctly responding to said stimuli. Using a more favorable reward is expected to positively influence motivation and performance of these animals in a specific behavioral task. The present study examined the effects of using a highly palatable caloric reward in lieu of standard water reward. It was hypothesized that a highly caloric reward solution would facilitate a faster rate of learning on animals completing a behavioral task involving detecting and responding to a correct auditory stimulus embedded within a series of distractor auditory stimuli. Mice were water-restricted and subjected to one of two reward treatment conditions upon correct licking behaviors during a target auditory tone. While the present study determined that a 10% sucrose solution has the capacity to act as a stimulus that promotes correct behavior due to its positive reinforcement properties, (d’ = 2.02), further experiments and larger sample sizes are required to fully quantify the efficacy of sucrose solution compared to traditional water rewards. By examining the effects of alternative reward treatments on performance in an auditory tone discrimination task, we can determine optimal treatment conditions in which mice learn most efficiently. These results could further elucidate the relationship between caloric intake, nutrition, and learning at large.

The Relationship Between Cholinergic and Noradrenergic Activity and Behavioral State

Presenter(s): John Francis—Biology

Faculty Mentor(s): Lindsay Collins, David McCormick

Session 5: The Wonders of the Brain

Observable changes in behavior result from complex network activity within the brain . Precise excitation and inhibition of neurons is partially regulated via neuromodulatory systems which regulate the behavior of other neurons, thereby producing observable changes in behavior . I plan to investigate the relationship between activity of two neuromodulatory cell types, cholinergic and noradrenergic neurons, and observable behavior in mice . Acetylcholine (ACh) and noradrenaline (NA) are produced and released by cholinergic and noradrenergic neurons, respectively, and have broad functions throughout the central nervous system . For instance, both ACh and NA neurons are more likely to fire during high arousal state, a physiological measure of alertness and attentiveness which is related to external metrics of brain state, like pupil diameter . My project will investigate the relationship between activity of ACh and NA neurons and arousal-linked behavior in three ways: 1) we will confirm the relationship between ACh and NA activity and arousal previously demonstrated in our lab and expand on this literature by including other behavioral measures such as whisker pad motion and tail motion in our analyses, 2) determine whether changes in ACh and NA activity precede or follow the onset of behavioral events, 3) determine the extent to which ACh or NA provides synchronous signals across the brain during arousal state fluctuations . Using systems neuroscience techniques such as intracranial viral injections, immunohistochemistry, and 2-photon microscopy, this project will further our current understanding of the relationship between ACh and NA activity and observable patterns of behavior in mice .

Imaging Glomerular Signaling of Unrestrained Olfactory Search in Mice

Presenter(s): Isabelle Cullen—Biology

Faculty Mentor(s): Matt Smear, David McCormick

Session: Prerecorded Poster Presentation

Olfaction is vital for many crucial animal behaviors such as social interaction, avoiding predators, and locating food . Our goal is to understand how an animal navigates toward the source of an odor . However, little is known about how odors are coded to inform olfactory search behavior . Air turbulence can cause odor distributions to be highly variable and unpredictable . Although we have previously characterized specific behavioral patterns in turbulent odor plumes, little is known about how odors are translated into movements . Our goal is to capture and understand the sensory input that informs these previously observed behaviors . We do this by injecting iGluSnFR, a fluorescent glutamate reporter, into the mitral cell layer of the olfactory bulb . This reporter tells us how glutamate released from olfactory sensory neuron terminals influences activity of mitral cells . iGluSnFR’s fast kinetics allows us to observe and measure glutamate levels as the mouse performs olfactory navigation . By revealing activity in olfactory sensory neurons during olfactory navigation, this technique can tell us how odor informs the mouse’s brain during active sampling . Following the development of this technique, we will image from iGluSnFR mice performing our olfactory search task to determine the neural computation that connects movement and sensation . Understanding how mice translate odor into behavior will inform our understanding of active sensory sampling behaviors in humans .

Altered Motor Response to Aversive and Attractive Odors as Potential Biomarker for Autism Spectrum Disorders

Presenter(s): Isabelle Cullen—Biology

Faculty Mentor(s): Matt Smear, David McCormick

Session 2: Cells R Us

Active sensing in olfaction is the modulation in sampling behavior (inhalation patterns, or sniffing)
to modulate sensory input . Previous studies in humans and mice observed pleasant odors are sampled at a higher inhalation magnitude, while aversive odors are sampled at lower magnitudes when compared to the clean air control . However, this sniffing modulation is not present in those with autism . Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behaviors, communication skills, narrowed interests, and repetitive behaviors . Rozenkrantz et al . (2015) showed that children with ASD did not modulate sniffing behavior to aversive or attractive odors despite correctly identifying odors as pleasant or unpleasant, suggesting an innate altered motor response rather than perceptual differences . While studying the basis of this behavior in humans is limited, we can access the neural mechanism that underlies this behavior through transgenic mouse lines . With the support of the Smear lab, we will repeat Rozenkratz’s (2015) paradigm using Fragile X-Knockout mice to investigate the neurological mechanisms driving this phenomenon along with orofacial movements during olfaction . Due to COVID-19, data collection is limited, however, we have developed a small raspberry pi based system combined with a camera to track orofacial movements through the experiment . We then use Deep Lab Cut, an AI network, to extract facial patterns and movements of the nose during olfaction . This work will establish a behavioral paradigm for studying autism-related symptoms in mice, and will thus lay the groundwork for understanding the neural mechanisms underlying this disorder, which may serve as a potential biomarker to aid in earlier detection .