Promoting Early Child Development: Improving Language Outcomes Through Reciprocal Interaction

Presenter: Alex Bui Neuroscience

Faculty Mentor(s): Andrea Imhof, Philip Fisher

(Virtual) Poster Presentation

The quality of early parent-child interactions has a powerful influence on early brain development.
In light of emerging literature associating responsive caregiving behaviors with children’s cognitive and socio-emotional development, recent prevent initiatives have aimed to promote responsive parenting behaviors through caregiver interventions . Promising preliminary evidence from the Filming Interactions to Nurture Development (FIND) intervention reveals that promoting the quality of parent-child interaction may enhance both parent functioning and child development, but the mechanism(s) of change underlying these improvements has not been directly evaluated. A limited number of studies have employed micro-social coding measures to quantify responsive caregiving behaviors on a moment-to-moment scale, and even fewer have investigated the downstream effects of these caregiving behaviors on child language outcomes. The two primary goals of this study were to 1) evaluate whether FIND significantly increases the frequency of balanced, reciprocal interaction and 2) examine the relationship between pre-post changes in dyadic reciprocity and child language outcomes. The results of this study support promoting parental contingent responsiveness as a viable intervention target and presents an innovative framework to examine latent effects of pre-post change across an intervention period.

Functional and Anatomical Properties of Cck Cells in the Medial Habenula

Presenter: Leah Blankenship − Neuroscience

Faculty Mentor(s): Dr. Emily Sylwestrak

(In-Person) Poster Presentation 

Previous research has shown that the medial habenula (MHb) is involved in many behaviors, such as stress, depression, addiction, and reward-guided behavior, but the organization of neurons driving these behaviors is unclear. MHb neurons have traditionally been divided into two groups based on expression of ChAT and Tac1 and studies have demonstrated that Tac1 cells are involved in rewardguided behavior. More recent work has suggested that the MHb contains additional cell types and Cck has been identified as a potential marker for a subset of Tac1 cells. In this project, I aim to confirm that Cck cells are a subset of Tac1 cells, as well as examine functional and anatomical differences between these two cell types. To examine RNA expression overlap between Cck and Tac1, I am conducting RNA in situ hybridization experiments. To examine Cck cell function, I am recording neural activity of Cck cells in mice during reward-guided behavior. To examine Cck anatomical projections, I am imaging fluorescently-labeled Cck axon projections. Preliminary results from experiments thus far suggest that Cck cells respond to withheld reward (similar to Tac1 cells) and appear to project through the interpeduncular nucleus, rather than stopping there like most Tac1 projections. Results from these experiments will inform future work in the MHb as researchers continue to study the cell types of the habenula, especially as potential targets for treatment of conditions like addiction or depression.

Does the breathing cycle modulate the orientation of our attention?

Presenter: Nayantara Arora − Neuroscience

Faculty Mentor(s): Ulrich Mayr, Domink Graetz

(In-Person) Poster Presentation

At any point in time, individuals either orient themselves to the outside world, or rely on their internal representations (i.e., memories) to guide behavior and actions. We investigated to what degree the respiratory cycle modulates spontaneous exploration of the environment. Specifically, we tested the hypothesis that the tendency to direct attention to an external cue for information is increased during inhalation and decreased during exhalation. Our research utilized a novel task-switching paradigm that assesses how participants decide between internal and external representations to guide action. Employing eye-tracking, we tracked when people turn to the environment for information while registering respiration using a chest belt. Contrary to the hypothesis, we found that participants tend to orient their attention internally during inhalation and are more likely to check external cues during exhalation. These findings are discussed using evidence from neuroscience into account. To our knowledge, this experiment is the first to examine the relationship between breathing and attentional shifts between internal and external stimuli. Our results demonstrate the coupling of higher-level cognitive functions with lower-level physiological oscillatory signals that are often considered noise. They also pave the way for the examination of the kind of breathing/cognition interactions that are often assumed in the context of meditative practices.

What is the genetic basis of evolution? Looking at the shape of the opercle bone in Alaskan stickleback fish

Presenter: Christina Wickman, Marine Biology

Poster: D-4

Mentor: Chuck Kimmel, Institute of Neuroscience

What is the genetic basis of evolution? For this study, we used the three spine stickleback fish, which is a model for evolution as both the ancestral and derived populations can be gathered, and crossed to form viable offspring. Our study concentrated on the facial bone known as the opercle and we hypothesized that the shape of the opercle was controlled by Mendelian genetics in a co-dominance relationship. To test this hypothesis a model was created and both the parent and F1 populations were land marked choosing 12 points along the bones edge and the variation between the points were graphed using Principle Component Analysis. From the land marking of the F1 progeny it appeared that the alleles were expressing a dominance relationship and based on our findings we revised our hypothesis proposing this. To test this hypothesis the F2 progeny were landmarked, but did not show a dominance relationship, so we again revised our hypothesis proposing that quantitative genetics are at work: where multiple genes are acting to form different regions of the opercle bone. From this we concluded that the opercle shape is specified by multiple genes acting on different areas of the bone and we can infer that the changing of these genes provides the basis for evolution of the opercle, which provides for more skeletal variation, which can be advantageous evolutionarily

The Use of Gateway® Cloning and Modified BAC Trangenesis to Study Zebrafish Craniofacial Development

Presenter:Wade Sugden, Nathan Johnson, Biology

Poster: C-8

Mentor: Mark Sasaki, Institute of Neuroscience

Transgenesis techniques have revolutionized the study of cellular, developmental, and molecular biology by allowing researchers to visualize the proteins they study and manipulate the expression of genes in vivo. Through the use of genetic regulatory elements, transgenes can be tailored to over-express genes of interest, label tissue-specific cell types, and express genes in atypical locations. When expressed in skeletal elements of the zebrafish (Danio rerio), transgenes can be used to explore cell behavior and the genetic pathways involved in craniofacial morphogenesis. Two methods in particular have streamlined the process of creating transgenic animals: Gateway®-mediated and BAC-mediated transgenesis. Here we discuss the use of both techniques to create zebrafish that express transgenes in craniofacial elements using the runx2b, sp7, col11a2, and sox10 promoters. These promoters were chosen because runx2b and sp7 mark bone at different time points during development, while col11a2 and sox10 serve as cartilage markers. In the future, these fish will be vital tools for conducting cell tracking experiments, distinguishing cell types, and expressing genes of interest in craniofacial structures to determine their function.

Genetic Interaction in the Developing Danio Rerio Jaw

Presenter: Braden Larson, Biology, Russian and Eastern European Studies (REES)

Poster: B-7

Mentor: Charles Kimmel, Institute of Neuroscience

Genes act in concert during animal development to form complex anatomical structures. For example, the jaw skeleton requires precise expression and interaction of a multitude of genes to develop correctly. Our research focuses on the gene endothelin-1 (edn1), which encodes a signaling molecule required for ventral jaw development in the zebrafish, Danio rerio. Because elements of the jaw remain in the edn1 mutant, we hypothesized that other genes function within the edn1 genetic pathway. To test this, we generated double mutant zebrafish, pairing the edn1 mutant allele with mutant alleles of candidate genes based on previous literature. We then analyzed the double mutant skeletons for evidence of genetic interaction, and discovered an enhanced phenotype in one of the double mutants. Specifically, mutants for edn1 and fibroblast growth factor-8a (fgf8a), a gene that encodes another signaling molecule, are missing a portion of their upper jaw, a phenotype not present in either single mutant. To investigate the cell biology behind this phenotype we imaged the cells that constitute the jaw precursor tissue in live transgenic zebrafish. Strikingly, the cells that give rise to this structure appear missing in double mutant fish. Furthermore, we used Fluorescent In Situ Hybridization to observe gene expression of edn1, fgf8a, and potential shared target genes in wild type and mutant embryos. We conclude that cross talk between edn1 and fgf8a signaling is required for development of the jaw skeleton.

Optogenetic Silencing of Parvalbumin-expressing Interneurons in Mouse Auditory Cortex: Mechanisms of Gain Modulationology (Neurobiology)

Presenter: Alexandra K. Hartman, Biology (Neurobiology)

Poster: B-4

Mentor: Michael Wehr, Institute of Neuroscience

Mammalian sensory systems detect relevant stimuli with remarkable sensitivity. This holds true in both high-and low-contrast sensory environments—that is, both when the signal an organism is trying to isolate (say, a pure tone or a visual object) is the strongest signal detected, or is detected in the context of irrelevant signals of equal intensity. The firing rate (‘output’) of a typical auditory neuron increases with stimulus intensity (‘input’). The rate-intensity function is not fixed: gain adjustments—an increase or decrease in response magnitude, relative to baseline—depend on the context in which the stimulus is presented. Contextual gain modulation is thought to be regulated by synaptic input from inhibitory interneurons, but little is known about the connection patterns and cell types that enable it. We use optogenetic tools to address this. Archaerhodopsin is a proton pump activated by yellow-green light. When illuminated, these pumps generate dramatic outward currents that hyperpolarize —or ‘silence’—the neurons in which they are expressed. We will obtain in-vivo recordings from single units in the auditory cortex of anesthetized transgenic mice, in which Archaerhodopsin is expressed in conjunction with Parvalbumin, a protein specific to cortical GABAergic interneurons. The shift in the rate-intensity function of pyramidal cells—before and after Parvalbumin interneurons are dropped from the network—will reveal the physical target(s) of synaptic inhibition.

Characterization of Inputs to Active Basolateral Amygdala Neurons after Different Behavioral Treatments

Presenter: Harrison Fontaine

Mentors: Leah Deblande and Clifford Kentros, Institute of Neuroscience

Poster: 22

Major: Biology and Human Physiology

The amygdala is a brain structure that is required for the acquisition and storage of fearful memories. In humans, abnormal amygdalar activity has been associated with post-traumatic stress disorder, anxiety, and depression.
One component of simple fear memory formation is the association of a fearful stimulus and an otherwise neutral predictive stimulus. This association occurs in the basolateral amygdala (BLA). While the main inputs to the BLA
are well characterized, the specific coding strategies these inputs use to convey information has not been detailed. We used transgenic mice in conjunction with a modified viral tracer to determine how the inputs to recently active BLA neurons varied after exposure to fear-inducing and non-fear-inducing situations, with the reasoning that if different inputs were labeled after different treatments, inputs must be employing a neuron-specific coding strategy. In addition, we examined the differential activity of neurons in the BLA that may be gating the formation of fear memories. We reasoned that if these neurons were differentially active between fear-inducing and non-fear-inducing situations, these neurons might indeed be gating fear memory formation. Our results supported the use of a neuron- specific coding strategy in BLA input regions, as well as the model of a subset of BLA neurons gating fear memory formation. These results elucidate aspects of fear memory circuitry, and thus have implications in treating fear circuit pathologies.

Effect of Reward Size on the Activity of Auditory Cortical Neurons

Presenter(s): Jardon Weems − Biology

Faculty Mentor(s): Santiago Jaramillo

Poster 3

Research Area: Neuroscience

Funding: Peter O’Day Fellowship in Biological Sciences

The neural pathways that allow an animal to select the actions it should take in response to a sound in order to get a reward are not well understood. Recent work in our lab indicates that neurons in the region of the striatum that receive inputs from the auditory cortex fire differently in response to a sound when the sound is paired with a large reward in contrast to a small reward. These data suggest that the auditory striatum may integrate information about sound and reward size in a way that could support sound-action association learning. The primary aim of this study was to determine if reward related modulation observed in the striatal neurons is already present in the inputs arriving from the auditory cortex. To investigate whether auditory cortex integrates information about reward size during decision-making, we examined the activity of auditory cortical neurons in six male wild type C57BL/6J mice. Via chronically implanted electrodes, the mice performed an auditory reward- change task in which the same sound and same action was paired with different amounts of reward. We found that 7.5% of sound responsive auditory cortical neurons were modulated by the amount of reward during the decision-making task. In addition, we found a number of neurons in the auditory cortex that responded to movement, 21.8% of which were modulated by reward size. Our previous research found that 13.9% of sound responsive neurons in the auditory striatum and 25.7% of movement responsive neurons in the auditory striatum were modulated by reward size. Together, our results suggest that auditory cortex contributes to the integration of information about reward size and auditory stimuli during decision-making, but to a lesser extent than the auditory striatum.

The Role Of Patterned Spontaneous Circuit Activity In Drosophila Neuronal Circuit Assembly

Presenter(s):Nelson Perez − Biology

Faculty Mentor(s): Arnaldo Carreira-Rosario, Chis Doe

Oral Session 2SW

Research Area: Natural sciences, Neuroscience, Biology, Developmental Biology

Funding: HHMI (Howard Hughes Medical Institute), SPUR Program

Neuronal networks become active before they are fully functional. This is known as patterned spontaneous network activity (PaSNA), an event characterized by quiescent periods followed by bursts of activity. Many studies have demonstrated the importance of PaSNA for proper neuronal circuit assembly. Yet, little is known about the mechanisms underlying PaSNA.
In the Drosophila ventral nerve cord (spinal cord for invertebrate counterpart) PaSNA occurs during late embryonic stages. During PaSNA, embryos exhibit intermittent episodes of uncoordinated motor activity that gradually mature into crawling waves. Concomitantly with wave maturation, more neurons become active during PaSNA. The identity of these neurons and function during PaSNA remains unknown. To identify which cells undergo PaSNA and their function during circuit assembly, we are screening for GAL4 lines, which maintain expression in small subsets of neurons from the onset of PaSNA until the circuit is fully assembled. We have identified several GAL4 lines suitable for our experiments. Using in vivo calcium imaging, we identified that the neurons labeled by one of these lines participates in PaSNA. Four other lines have been identified as good candidates for future experiments that involve calcium imaging and tracking of synapsis formation during PaSNA. This represents a unique tool to study PaSNA and its role in circuit formation.