Thesis Seminars

Aishwarya Jayan - PhD Candicate

Knowing when and where to direct our visual attention is critical to functioning in a complex world. For example, if we attend exactly at the moment when a tennis ball will be in an ideal location, we can better achieve our ideal outcome of hitting it with our racket. Spatial attention (where to attend) has been studied extensively, including in naturalistic contexts. However, temporal attention (when to attend) has primarily been studied in the context of low-level visual discrimination tasks, such as distinguishing between gratings of different orientations, and with attentional deployment limited to only a couple of seconds into the future. This leaves unexplored the crucial gap between prior work on temporal attention and the reality of how naturalistic temporal attention works, whether that means hitting the tennis ball at the right moment or paying attention to important moments during conversations in our daily lives. To address this problem, I propose to study the behavioral (psychophysics) and neural (functional magnetic resonance imaging, fMRI) mechanisms of voluntary temporal attention on ecologically relevant timescales (ranging from seconds to minutes) and as it applies to a variety of stimuli, ranging from gratings, to objects, scenes, and faces, and to naturalistic audiovisual stories. I hypothesize that (1) temporal attention can be cued on a longer timescale than previously shown (~1.5 sec); and that (2) temporal attention can be cued across highly complex stimuli, such as objects, scenes, faces, and naturalistic narratives. Furthermore, for naturalistic narratives, I predict that successful deployment of temporal attention for a specific story moment will result in improved perception and in memory facilitation not just for the cued moment, but also for the entire encompassing event (tens of seconds to minutes) that the key moment is a part of in the broader narrative. The feasibility of my paradigm is supported by foundational prior work on temporal attention, which provides evidence for improved visual perception due to temporal attention cueing. Further, prior work on event perception and episodic memory for narratives has shown that timing and predictability are crucial elements to both processes, and I expand upon and manipulate these aspects of the stimuli in my study. In Aim 1, I will determine the timescale limitations of temporal attention using a visual discrimination task with gratings. In Aim 2, I will explore the effects of deploying temporal attention at multiple timescales in the context of complex visual stimuli, including faces, objects, and scenes. Finally, in Aim 3, I will examine how deploying temporal attention to specific moments of complex audiovisual naturalistic narratives (e.g., a plot point of a TV show episode) affects perception and memory for those moments and for other high-level components of those narratives, such as characters, plots, and events. Successful completion of these aims will help shed light not only on the behavioral and neural mechanisms of temporal attention for complex stimuli and ecologically relevant timescales but will also offer a new approach for examining the effects of attentional cueing on naturalistic event perception and memory. In sum, our proposed study seeks to bring us closer to understanding the real-world implications of temporal attentional deployment.

 Sep 17, 2025 @ 2:00 p.m.
 Medical Center | 1-7619 Lower Adolph Aud.

Thomas Scudder - PhD Candidate

Protein Phosphatase 2A (PP2A) is directly responsible for over 40% of serine/threonine dephosphorylation events in mammalian cells. Though it lacks intrinsic substrate specificity, PP2A achieves precise spatiotemporal regulation through assembly with diverse regulatory adaptor subunits. The canonical holoenzyme comprises a catalytic C-subunit (PPP2C), a scaffolding A-subunit (PPP2R1), and a substratetargeting B-subunit. PPP2R5D (B56δ) is one such adaptor, critical for intracellular localization and activity, yet its full repertoire of targets and mechanisms remains undefined. The human de novo E420K and E198K mutations in PPP2R5D produce neurological symptoms, including intellectual disability, seizures, and autism spectrum disorder (collectively termed Jordan’s Syndrome), with underlying molecular mechanisms that are largely unknown. K+/Cl- co-transporter 2 (KCC2) is neuron-specific, and its activity, surface expression, and localization are tightly regulated through multiple mechanisms, notably phosphorylation at several sites including Serine 940 (S940). KCC2 S940 is phosphorylated by PKC and canonically dephosphorylated by PP1 via scaffolding by LMTK3. Through this regulation, KCC2 maintains intracellular [Cl-] homeostasis, and its dysregulation results in aberrant neuronal activity, including impaired GABAergic inhibition, causing pathogenic hyperexcitability and behavioral deficits that parallel symptoms seen in patients with the de novo PPP2R5D mutations that result in Jordan’s Syndrome. This project aims to determine if human de novo mutation variants of the PPP2R5D-PP2A holoenzyme exhibit rogue activity on KCC2-pS940, resulting in hyperexcitability and reduction or reversal of normal GABAA receptor inhibitory function. To model these effects, I will employ PPP2R5D knockout (+/- and -/-) and heterozygous knock-in (E198K/+ and E420K/+) mice. Using these models, I will determine if PPP2R5D mutations directly alter KCC2-pS940 levels in neurons, investigate whether PPP2R5D mutations cause hyperexcitability via disrupted [Cl-] homeostasis, and test whether a KCC2 activator rescues the neuronal hyperexcitability, cognition, and social interaction deficits seen in mouse models. These studies will advance understanding of PPP2R5D function, how its mutations affect PP2A activity and neuronal signaling, and inform therapeutic development for PPP2R5Drelated intellectual disability.

 Sep 19, 2025 @ 1:00 p.m.
 Medical Center | K307 (3-6408)

Stacey Pedraza - PhD Candidate

Houge-Janssens syndrome-1 (HJS1), also called Jordan’s syndrome, is a rare neurodevelopmental disorder resulting from de novo mutations in the PPP2R5D gene. This gene encodes one of the many regulatory B subunits of protein phosphatase 2A (PP2A). PP2A is a critical heterotrimeric holoenzyme, responsible for more than 40% of all serine/threonine-specific dephosphorylations in the central nervous system (CNS). HJS1 mutations (E198K and E420K) lead to severe intellectual disability disorder (IDD), autism, seizures, and other pathological phenotypes such as aberrant white matter brain structure. Alterations in brain structure and function suggest the imbalance of excitatory and inhibitory (E/I) neural activity, which may result in defective neuroplasticity. Previous studies have demonstrated that neuronal activity regulates callosal myelination, a critical process for the rapid propagation of action potentials and modulation of neuroplasticity. Aberrant neuronal activity, such as the imbalance of E/I, may alter activity-regulated myelination. Consistently, we found that HJS1 mouse models exhibit increased neuronal excitability and callosal myelination, suggesting altered brain structure and function. However, the underlying molecular mechanisms involved in HJS1 mutations regulating myelination remain poorly understood. This study will test the hypothesis that severe HJS1 mutations trigger activity-dependent myelination to promote maladaptive myelination of axons in the corpus callosum via the BDNF (neuron) – TrkB (OPC/OL) signaling pathway. We will use heterozygous knock-in mouse models of severe HJS1 mutations that mimic the human disease state and exhibit aberrant neuronal activity to address how HJS1 mutations translate to increased callosal myelination. In Aim 1, I will test our hypothesis that severe HJS1 mutations increase callosal axon myelin sheath thickness. In Aim 2, I will test the prediction that increased neuronal excitability in HJS1 mouse models contributes to the enhanced callosal myelination. Furthermore, I will determine whether BDNF (neuron) – TrkB (OPC/OL) signaling mediates HJS1’s effect on promoting callosal myelination. This study will help define the cellular signaling pathways disrupted in HJS1 that contribute to the pathophysiology and provide valuable insight for understanding the underlying molecular mechanisms involved in activity-regulated myelination in normal and disease states, such as IDD and seizures.

 Sep 25, 2025 @ 1:00 p.m.
 Medical Center | K307 (3-6408)