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Student Seminars

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NSC 503 Seminars

Daulton Myers; Margaux Masten - PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Wei Hsu & David Dodell-Feder

 Apr 03, 2023 @ 4:00 p.m.
 Medical Center | K-307

Thesis Proposal: TG2 is fundamental for controlling the response of astrocytes to injury and their ability to support neuronal health in injury contexts

Thomas Delgado - PhD Candidate, Advisor: Gail Johnson, PhD

Astrocytes are essential for maintaining neuronal function in resting and disease states. Following injury, astrocytes take on reactive phenotypes that grade from neurotoxic to neuroprotective, which impact subsequent neuronal recovery processes, such as axonal regeneration. Only recently has the heterogeneity of reactive astrocyte populations begun to be described, and little is known about the contextual requirements and molecular inflection points that underlie these graded responses. Accumulating data from my lab suggests that one of these inflection points is transglutaminase 2 (TG2). TG2 is complex in that it regulates signaling of numerous molecular pathways at the cell membrane, in the cytosol, and in the nucleus; thus, it can provide multiple levels of context-dependent input into gene regulation. Importantly, when TG2 is depleted from astrocytes, they better protect neurons in culture from oxygen-glucose deprivation (OGD), improve motor function recovery in a mouse spinal cord injury model, and better facilitate neurite outgrowth in vitro on an injury-relevant, growth-inhibitory matrix. Additionally, TG2 depletion upregulates lipid handling (lipid uptake and formation of lipid droplets) and lipid metabolism pathways in an injury-dependent manner. As stressed neurons accumulate reactive oxygen species and peroxidated lipids, and cannot metabolize these toxic lipids on their own, they export them to astrocytes. Astrocytic lipid uptake and metabolism eliminates these oxidized lipids and recycles them to produce energy substrates for neurons. This mechanism may partly underlie the protective effect of TG2-/- astrocytes after injury.

In aim 1, I will test the hypothesis that depletion of astrocytic TG2 improves axonal regeneration through an inhibitory extracellular matrix (ECM) after CNS injury using an optic nerve crush model in mice. These studies are built on previous spinal cord injury data from my lab, with the unique addition that, in the optic nerve, axonal regeneration can only occur through the inhibitory ECM deposited at the crush site, while in the spinal cord, regrowth may occur via collaterals around the injury site, through permissive matrices.

In aim 2, I will identify the major molecular pathways and mechanisms of gene and protein regulation underlying the unique function of TG2-/- astrocytes. As TG2 is a known interactor of transcription machinery and chromatin regulators in the nucleus, I will use ATAC-seq to analyze differences in chromatin accessibility between TG2-/- and wild type (WT) astrocytes and integrate these data with differentially regulated transcripts identified through RNA sequencing. I will compare differential enrichment in upstream signaling pathways with differential protein expression identified by tandem mass spectrometry to better approximate the functional impact of these molecular changes.

In aim 3, following data that lipid handling and metabolism is differentially regulated in TG2-/- astrocytes, I hypothesize that TG2-/- astrocytes more efficiently uptake and metabolize lipids that are released by stressed neurons (as peroxidated lipids), ultimately providing better control of oxidative stress and increased energy supply to neurons in injury conditions. Therefore, I will measure the ability of WT and TG2-/- astrocytes to take up and metabolize lipids released by neurons, in control and stressed conditions, as indicated by lipid droplet accumulation. Further, I will measure metabolic flux through ketone and cholesterol synthesis pathways, downstream of fatty acid oxidation, in WT and TG2-/- astrocytes by labeling them with C13-palmitate and measuring C13-labeled metabolites by LC-MS. I will then pair neurons with either astrocyte group to track the export of C13-labeled energy substrates to neurons.

Overall, this project will explore the role of TG2 as a key regulator of astrocyte reactivity after CNS injury and, within this scope, better characterize the astrocytic metabolic pathways that are integral for neuronal and functional recovery.

 Apr 07, 2023 @ 2:00 p.m.
 Medical Center | Lower Adolph Auditorium (1-7619)

NSC 503 Seminars

Andrea Campbell; Dominic Bunn - PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Jude Mitchell & Gail Johnson

 Apr 10, 2023 @ 4:00 p.m.
 Medical Center | K-307

Thesis Defense: Structure and Function of Corticogeniculate Feedback

Allison Murphy - PhD Candidate, Advisor: Farran Briggs, PhD

In the visual system, information enters as light hitting the retina of the eye. This signal is transmitted to the dorsal lateral geniculate nucleus (LGN) in the thalamus, then to primary visual cortex (V1). In highly visual animals, this feedforward visual pathway is organized into parallel informational streams, known as the magnocellular, parvocellular, and koniocellular streams in primates and the somewhat homologous X, Y, and W streams in carnivores, including ferrets. While these feedforward stream have been extensively studied, relatively little is known about the corticogeniculate (CG) feedback pathway that projects from V1 to the LGN. Although corticogeniculate feedback synapses in the LGN greatly outnumber feedforward retinal inputs, their modulatory nature has made their functional role difficult to study. The purpose of this thesis is to examine the structure of this pathway and its functional role in vision by answering the following questions: 1) Is a parallel stream structure maintained in the feedback pathway? 2) What is the functional impact of feedback in the LGN? To answer these questions, we performed neurophysiological recordings simultaneously in LGN and V1 of anesthetized animals. For the first question, we found functionally connected pairs of corticogeniculate and LGN neurons using cross-correlation of their spike trains. We analyzed the physiological response properties of these pairs of neurons to determine whether distinct populations of CG neurons maintain stream-specific projections to the LGN. Additional anatomical analyses provide support for distinct morphological subtypes of CG neurons. For the second question, we used a modified rabies virus to selectively infect corticogeniculate neurons with a light sensitive ion channel and performed optogenetic manipulation during presentation of visual stimuli. We then examined how manipulation of corticogeniculate feedback affected visual response properties of LGN neurons, including the variability and information content of their spike trains. Together, these experiments demonstrate that corticogeniculate feedback is a pathway with a complex organizational structure that plays a subtle role in shaping LGN visual responses.

 Apr 11, 2023 @ 11:00 a.m.
 Medical Center | K-307 (3-6408)

Neuroscience Retreat
Keynote: The shape of the world – representation of 3D versus 2D shapes in visual area V4

Kristina Nielson, PhD - Associate Professor, Neuroscience, Johns Hopkins University

Register Here

 Apr 14, 2023 @ 8:30 a.m.
 Memorial Art Gallery | 

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NSC 503 Seminars

Claire Lim; Tanique McDonald - PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Margot Mayer-Proschel & Jean Bidlack

 Apr 17, 2023 @ 4:00 p.m.
 Medical Center | K-307

NSC 503 Seminars

Alexis Feidler; Estephanie Balbuena - PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Erika ANderson & Dragony Fu

 Apr 24, 2023 @ 4:00 p.m.
 Medical Center | Ryan Case Method Room

NSC 503 Seminars

Linh Le; Matt Adusei - PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Brian Keane & Juliette McGregor

 May 01, 2023 @ 4:00 p.m.
 Medical Center | K-207

NSC 503 Seminars

Lia Calcines Rodriguez; Renee Miller, PhD - TA Opportunities; PhD Candidate, Neuroscience Graduate Program

Faculty Evaluators: Krishnan Padmanabhan & Martina Poletti

 May 08, 2023 @ 4:00 p.m.
 Medical Center | K-207

TBA

Dean Salisbury, PhD - Director Clinical Neurophysiology Research Lab, Professor of Psychiatry, University of Pittsburgh

 May 18, 2023 @ 4:00 p.m.

Host: John Foxe

TBA

Yoland Smith, PhD - Division Chief, Neuropharmacology and Neurology Disease, Emory National Primate Research Center

 Jun 01, 2023 @ 4:00 p.m.

Host: John Foxe