Neuroscience and Neurobiology Commons^™

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Dissecting The Tissue-Specific Contributions To Seizures, Cardiorespiratory Dysfunction, And Sudden Death In The Kv1.1 Mouse Model Of Epilepsy Using Conditional Knockout Approaches, Kelsey Paulhus

Biological Sciences Theses and Dissertations

Sudden unexpected death in epilepsy (SUDEP), the primary cause of mortality in epilepsy, remains poorly understood. Studies suggest seizures may trigger dangerous signals affecting the heart and lungs leading to collapse and death. The Kv1.1 deficiency mouse model mirrors clinical SUDEP cases, showing spontaneous seizures, cardiorespiratory issues, and premature death. However, this model lacks regional specificity in Kv1.1 deletion, hindering insights into SUDEP’s mechanisms and anatomical substrates.

This dissertation employs three distinct conditional knockout (cKO) techniques to investigate the individual roles for the forebrain, brainstem, and heart in SUDEP related phenotypes. The findings reveal that the forebrain alone can trigger …

The Correlates Of Neurobiology And Lived Experiences Of Music-Induced Bonding, Empathy, And Shared Flow, Ashley Marie Sherwood

Masters Theses

An alarming decline in mental health and increase in addiction and substance use disorders over the last few decades have generated increased interest in exploring how improved social health in the community could be a protective factor against mental health crises. Interventions which increase perceived emotional synchrony and shared flow may positively impact the social fabric of society. This paper examines the relationship between self-reported perceptions of emotional synchrony and shared flow and changes in measures of cortisol, dopamine, oxytocin, and vasopressin in blood samples following musical improvisation, with a review of relevant literature also presented. Vasopressin was found to …

Targeting Cholinergic Signaling In Glioblastoma, Sumyuktha Vijay Anand

Dartmouth College Ph.D Dissertations

Primitive stem cell-like populations that are prone to malignant transformation reside in the brain throughout adulthood. My lab’s reports and many others have characterized subsets of glioma cells reminiscent of adult stem-like cells implicating them rational candidates for cell-targeted therapies. Emerging evidence suggests that the neurotransmitter microenvironment influences these stem-like cells during glioma progression providing an inroad to study neuromodulators in glioma. Some glioma stemlike cells share characteristics with adult tissue oligodendrocyte progenitor cells. Primitive cells of the oligodendroglial lineage express muscarinic acetylcholine receptors (mAChRs), and their “stemness” is maintained by the acetylcholine (ACh) neurotransmitter. Here, I conduct transcriptomic, electrophysiological, …

Beneficial Effects Of Exercise On Glial Cell Line-Derived Neurotrophic Factor Content And Endplate Morphology In Skeletal Muscle Of Aging Male And Female Rats, Juliana M. Vangyseghem

Dissertations

Premenopausal women display lower incidence and severity of neurological disease compared to men of the same age, yet these populations are often treated similarly. A decline in neuromuscular function is associated with aging, which may be partially explained by a decline in neurotrophic factor expression with age. A possible way to maintain neuroprotection would be to regulate the production and release of a target-derived neurotrophic factor, such as glial cell line-derived neurotrophic factor (GDNF). GDNF has been shown to be the most potent survival factor for motor neurons and GDNF content of skeletal muscle has been shown to increase with …

Brainlife.Io: A Decentralized And Open-Source Cloud Platform To Support Neuroscience Research, Soichi Hayashi, Bradley A. Caron, Anibal Solon Heinsfeld, Sophia Vinci-Booher, Brent Mcpherson, Daniel N. Bullock, Giulia Berto, Guiomar Niso, Sandra Hanekamp, Daniel Levitas, Kimberly Ray, Anne Mackenzie, Paolo Avesani, Lindsey Kitchell, Josiah K. Leong, Filipi Nascimento-Silva, Serge Koudoro, Hanna Willis, Jasleen K. Jolly, Derek Pisner, Taylor R. Zuidema, Jan W. Kurzawski, Kyriaki Mikellidou, Aurore Bussalb, Maximilien Chaumon, Nathalie George, Christopher Rorden, Conner Victory, Dheeraj Bhatia, Dogu Baran Aydogan, Fang-Chen F. Yeh, Franco Delogu, Javier Guaje, Jelle Veraart, Jeremy Fischer, Joshua Faskowitz, Ricardo Fabrega, David Hunt, Shawn Mckee, Shawn T. Brown, Stephanie Heyman, Vittorio Iacovella, Amanda F. Mejia, Daniele Marinazzo, R. Cameron Craddock, Emanuale Olivetti, Jamie L. Hanson, Eleftherios Garyfallidis, Dan Stanzione, James Carson, Robert Henschel, David Y. Hancock, Craig A. Stewart, David Schnyer, Damian O. Eke, Russell A. Poldrack, Steffen Bollmann, Ashley Stewart, Holly Bridge, Ilaria Sani, Winrich A. Freiwald, Aina Puce, Nicholas L. Port, Franco Pestilli

Psychological Science Faculty Publications and Presentations

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Low-Dimensional Criticality Embedded In High-Dimensional Awake Brain Dynamics, Antonio J. Fontenele, J. Samuel Sooter, V. Kindler Norman, Shree Hari Gautam, Woodrow L. Shew

Physics Faculty Publications and Presentations

Whether cortical neurons operate in a strongly or weakly correlated dynamical regime determines fundamental information processing capabilities and has fueled decades of debate. We offer a resolution of this debate; we show that two important dynamical regimes, typically considered incompatible, can coexist in the same local cortical circuit by separating them into two different subspaces. In awake mouse motor cortex, we find a low-dimensional subspace with large fluctuations consistent with criticality—a dynamical regime with moderate correlations and multi-scale information capacity and transmission. Orthogonal to this critical subspace, we find a high-dimensional subspace containing a desynchronized dynamical regime, which may optimize …

The Nuclear Import Receptor Kapβ2 Modifies Neurotoxicity Mediated By Poly(Gr) In C9orf72-Linked Als/Ftd, Maria Elena Cicardi, V. Kankate, Sindhu Sriramoji, Karthik Krishnamurthy, S. S. Markandaiah, B. M. Verdone, Amandeep Girdhar, A. Nelson, L. B. Rivas, A. Boehringer, Aaron R. Haeusler, Piera Pasinelli, Lin Guo, Davide Trotti

Farber Institute for Neuroscience Faculty Papers

Expanded intronic G₄C₂ repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapβ2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapβ2 is detrimental to their survival, whereas increased Kapβ2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapβ2 levels …

Understanding Refractory Status Epilepticus With Novel Hd-Mea Technology, Isaac Stubbs, Ryley Parrish, Melissa Blotter, Max Holmes, Skyler Russell

Library/Life Sciences Undergraduate Poster Competition 2024

3rd Place Oral Presentation

Status Epilepticus (SE) is a severe medical condition marked by continuous seizures lasting over 5 minutes. When SE becomes resistant to anticonvulsant drugs, the condition is known as Refractory Status Epilepticus (RSE), which lacks effective treatments and has a mortality rate of 38%. RSE lacks effective treatments partially due to our limited understanding of the mechanisms that lead to patient antiepileptic drug resistance.

Ivermectin Activates Striatal Cholinergic Interneurons To Enhance Dopamine Release, Tyler Love, Jordan Yorgason, Hillary Wadsworth, Alicia Warnecke, Joshua Barlow, Emma Steimle, Joakim Ronström, Pacen Williams, Christopher Galbraith, Jared Baldridge, Michael Jakowec, Daryl Davies

Library/Life Sciences Undergraduate Poster Competition 2024

• The substantia nigra compacta releases dopamine into the dorsal striatum, a brain region associated with movement and motivation

• Cholinergic interneurons in the dorsal striatum can directly cause dopamine release

• IVM is a known positive allosteric modulator of P2X4 receptors as well as nicotinic

• acetylcholine receptors

• Ivermectin is known to affect many dopamine linked behaviors, but no studies have been conducted to determine if Ivermectin is able to modulate dopamine release

The Cold Hard Truth: Cryopreserved Tissue Is Superior To Ffpe Tissue In Molecular Analysis, Delaney Anderson, Jeffrey Okojie, Mackenzie Burr, Peyton Worley, Isaac Parker, Jack Davis, Bridger Kearns, Jared Barrott

Library/Life Sciences Undergraduate Poster Competition 2024

Personalized cancer care requires molecular characterization of neoplasms. While the research community accepts frozen tissues as the gold standard analyte for molecular assays, the source of tissue for all testing of tumor tissue in clinical cancer care comes almost universally from formalin-fixed, paraffin-embedded tissue (FFPE). Specific to genomics assays, numerous studies have shown significant discordance in genetic information obtained from FFPE samples and cryopreserved or flash frozen samples. To explain the discordance between FFPE samples and cryopreserved samples, a head-to-head comparison between FFPE and cryopreserved tissues was performed to analyze the DNA yield, DNA purity and DNA quality in terms …

Adapting The Auxin-Inducible Degron (Aid) System To The Zebrafish Model Organism, Dennis Li

Library/Life Sciences Undergraduate Poster Competition 2024

The Auxin Inducible Degron (AID) system is a conditional and reversible protein degradation system naturally occurring in plants. In the presence of the hormone Auxin, the AID tagged proteins are recruited into the plant’s E3 ubiquitin ligase machinery, ubiquitinated, and marked for degradation1. To adapt the AID system to the zebrafish model organism, our lab generated lines co-expressing Arabidopsis Thaliana plant TIR1 protein and GFP tagged with AID (GFP-AID) in superficially-located mechanosensory hair cells (HC) of the lateral line system and in spinal cord neurons found deeper in the body. Upon auxin application, GFP-AID expressed in the superficial HCs was …

Effects Of Methamphetamine On Microglia Through Reactive Oxygen Species, Chase Seiter, Jordan Yorgason, Nathan Sheets, James Blood, Lydia Hawley, Erin Taylor, Eliza White, Hillary Wadsworth, Jason Hansen

Library/Life Sciences Undergraduate Poster Competition 2024

▪ Dopamine release in the Nucleus Accumbens (NAc) underlies motivational behavior for methamphetamine (METH) reward.

▪ ATP is a chemoattractant to microglia and is METH on ATP release and clearance are unknown.

▪ Furthermore, METH is known to produce reactive dopamine terminal function, microglia morphology and METH interactions are unknown.

Zmp-Induced Activation Of Ampk Enhances Accumbal Dopamine Function, Isabella Roque, Jordan Yorgason, Rachel Campbell, Serin Baker, Jared Mcfarlane, Oliver Saunders, David Thomson

Library/Life Sciences Undergraduate Poster Competition 2024

Oral Presentation Honorable Mention

• Dopamine terminal function is associated with motivation

• Fasting activates AMPK, a cellular sensor that measures intracellular AMP relative to ATP

• AMPK activation is a target of interest for age related cognitive decline, prevention of muscle wasting, etc.

• ZMP is an endogenous nucleotide AMP mimetic that activates AMPK

• The present study examined the novel precursor ZMP compound called P39 using an ex vivo mouse model

Effects Of Predation On Cognition In Brachyrhaphis Rhabdophora, Elizabeth F. Jenkins, Jerry B. Johnson

Library/Life Sciences Undergraduate Poster Competition 2024

RESEARCH QUESTION

Does “predation environment” affect the cognitive abilities of the tropical fish Brachyrhaphis rhabdophora?

Determining If Optic Tecti Of Larval Zebrafish Receive Input From Deep Brain Photoreceptors, Emalie A. Christensen, Allison G. Pickens, Colby Odom, Griffin Sauer, Sarah Y. Jarrett, Maurice Hunt, Annalie Martin, Arminda Suli

Library/Life Sciences Undergraduate Poster Competition 2024

Deep brain photoreceptors (DBPs) are light-responsive sensory cells present in mammals and non-mammalian vertebrates. In non-mammalian vertebrates, studies have shown DBP involvement in various time and light dependent behaviors including circadian rhythm, phototaxis, and seasonal reproduction. In adult telosts, DBPs are present throughout the brain, including the optic tectum (OT), a midbrain structure that receives and integrates input from multiple sensory modalities. In this study, we aimed to determine if DBPs are part of or send input to the OT of larval zebrafish. Single-cell RNA sequencing of the larval zebrafish OT showed the presence of several opsins. We focused on …