Neurosciences Commons^™

Dopamine-Endocannabinoid Crosstalk Drives Exercise-Induced Bidirectional Plasticity In Parkinson's Disease, Federica Campanelli, Gioia Marino, Giuseppina Natale, Maria De Carluccio, Tabitha N. Rodriguez, Michelle Smeyne, Richard Jay Smeyne, Veronica Ghiglieri, Paolo Calabresi

Department of Neuroscience Faculty Papers

Parkinson’s disease (PD) is a neurodegenerative disorder marked by loss of substantia nigra dopaminergic neurons. Epidemiological evidence indicates that lifelong physical activity reduces both PD incidence and slows disease progression. Here, we examine how voluntary exercise induces long-lasting neuroprotection of the corticostriatal function in a murine model of α-synuclein–driven nigrostriatal pathology. In preformed fibril (PFF)-injected mice, long-lasting voluntary wheel running prevents degeneration of nigrostriatal dopaminergic terminals and improves motor performances. Intensive exercise normalizes spontaneous glutamatergic transmission and preserves corticostriatal long-term potentiation (LTP) in striatal spiny projection neurons. Exercise-induced LTP is dependent on activation of dopamine (DA) DA1, GluN2B-expressing NMDA and …

Disruption Of The Lrrk2 Substrate Rab12 Facilitates Neurotransmission And Causes Hyperactivity In Mice, Xingjian Li, Yuanxin Chen, Huaixing Wang, Xue Zhang, Noah Guy Lewis Guiberson, Xianting Li, Jacqueline Burré, Junmin Peng, Hui Zhang, Zhenyu Yue

Department of Neuroscience Faculty Papers

RAB12 is a small GTPase and a validated substrate of LRRK2, a kinase genetically linked to Parkinson's disease (PD). While RAB12-LRRK2 signaling has been implicated in ciliogenesis and immune regulation, the neuronal function of RAB12 remains largely unexplored. Here, we investigated the role of RAB12 in synaptic physiology using Rab12 knockout (KO) mice. Rab12 KO mice developed normally but exhibited increased locomotor activity in adulthood. Electrophysiological recordings from striatal slices revealed enhanced presynaptic release probability and increased excitatory drive onto medium spiny neurons. Consistently, live-cell imaging of cultured cortical neurons revealed that Rab12 deletion facilitated, while Rab12 overexpression inhibited, synaptic …

Protocol For Inducing Focal Striatal Stroke In Mice Using Photothrombosis, Bridget R. Boyle, Eileen Collyer, Andrea P. Berghella, Elena Blanco-Suarez

Department of Neuroscience Faculty Papers

Here, we present a protocol for inducing focal striatal stroke in mice using photothrombosis. We describe steps for photothrombotic striatal surgery, magnetic resonance imaging, open field behavioral assessment of stroke-induced motor deficits, and post-stroke monitoring. We then detail procedures for tissue collection and immunofluorescence. This protocol provides a standardized approach for consistently modeling striatal stroke in mice, enabling mechanistic studies and preclinical therapeutic testing.

Protein-Protein Interaction–Interfering Peptide Rescues Dysregulated Nmda Receptor Signaling, Robert E. Featherstone, Hongbin Li, Ameet S. Sengar, Karin E. Borgmann-Winter, Olya Melnychenko, Lindsey M. Crown, Ray L. Gifford, Felix Amirfathi, Anamika Banerjee, Aivi Tran, Krishna Parekh, Margaret Heller, Wenyu Zhang, Robert J. Gallop, Adam D. Marc, Pragya Komal, Michael W. Salter, Steven J. Siegel, Chang-Gyu Hahn

Farber Institute for Neuroscience Faculty Papers

The complex and heterogeneous genetic architecture of neuropsychiatric illnesses compels us to look beyond individual risk genes for therapeutic strategies and target the interactive dynamics and convergence of their protein products. A mechanistic substrate for convergence of synaptic neuropsychiatric risk genes are protein-protein interactions (PPIs) in the N-methyl-D-aspartate receptor (NMDAR) complex. NMDAR hypofunction in schizophrenia is associated with hypoactivity of Src kinase, resulting from convergent alterations in PPIs of Src with its partners. Of these, the association of Src with PSD-95, which inhibits the activity of this kinase in the NMDAR complex, is known to be increased in schizophrenia. Here, …

How Patients With Amyotrophic Lateral Sclerosis Perceive Respiratory Interventions: A Mixed-Methods Study To Inform Implementation Efforts, Jason Ackrivo, Danny Bracy, Lauren B. Elman, John Hansen-Flaschen, Zachary Simmons, Piera Pasinelli, Terry Heiman-Patterson, Steven M. Kawut, Meghan B. Lane-Fall

Department of Neuroscience Faculty Papers

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that commonly leads to respiratory failure. Early respiratory interventions that may improve symptoms and outcomes are underused when prescribed. We sought to characterize patient perspectives and preferences for respiratory care to enable identification of implementation strategies to improve the uptake of ALS respiratory interventions.

METHODS: A prospective multicenter mixed-methods observational study was conducted using semistructured interviews of participants recently diagnosed with ALS at 4 academic centers in the United States. Eligible patients were those with an ALS diagnosis in the previous 12 months, forced vital capacity < 80% predicted normal, or presence of dyspnea or orthopnea.

RESULTS: Twenty-four patients …

Intranasal Delivery Of Extracellular Vesicles Derived From Human Bone Marrow Mesenchymal Stem Cells Dampens Neuroinflammation And Ameliorates Motor Deficits In A Mouse Model Of Cortical Stroke, Saviana Antonella Barbati, Chiara D'Amelio, Chiara Feroleto, Marta Morotti, Ida Nifo Sarrapochiello, Francesca Natale, Domenica Donatella Li Puma, Yolanda Gomez-Galvez, Elena Blanco-Suarez, Lorraine Iacovitti, Lucia Leone, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi

Department of Neuroscience Faculty Papers

Early treatment of ischemic stroke can significantly reduce disability and mortality rates. Stem cell-derived extracellular vesicles (EVs) have shown potential as therapeutics for neurological disorders. This study explored whether intranasal administration of EVs from human bone marrow mesenchymal stem cells (BM-MSCs) enhances forelimb motor function recovery in a mouse model of motor cortex stroke and investigated their mechanism of action, focusing on neuroinflammation. C57BL/6JRj mice received EV treatment of 0.1 × 10⁹ EVs per dose per day, 48 h post-stroke and twice weekly for four weeks. EV-treated mice showed significant improvement in forelimb deficits, as evaluated using a series …

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Er Stress Tolerance Is Regulated By Copper-Dependent Perk Kinase Activity., Sarah E. Bond Newton, Xinglong Shi, Noah R. Beratan, Julia Perhacs, Jitendra K. Arya, Margaret K. Bond, Tali Gidalevitz, Cagla Akay-Espinoza, Donita C. Brady, Kelly L. Jordan-Sciutto

Farber Institute for Neuroscience Faculty Papers

Pancreatic/PKR-like endoplasmic reticulum (ER) kinase (PERK) is a kinase that, in response to ER stress, mediates dual homeostatic and pro-apoptotic signaling. Thus, intricate regulation is required for physiological function. Attempts to modulate PERK activity have shown that the determinants of adaptive vs. maladaptive signaling remain ambiguous. Here, with purified protein, we provide evidence that PERK binds copper, identifies residues required for interaction, and demonstrates that copper is necessary for kinase activity. Furthermore, cellular PERK activity can be modulated via copper availability, and this regulatory relationship can be manipulated to dictate ER stress tolerance. Critically, these phenomena translate to phenotypes in …

Open Field Two-Texture Preference Testing Is Not Associated With The Neuropathic Pain-Like Phenotype That Occurs Following Mouse Cervical Contusion Spinal Cord Injury, David A. Jaffe, Megan A. Lyttle, Angelo C. Lepore

Farber Institute for Neuroscience Faculty Papers

Development of neuropathic pain (NP) is one of the major complications associated with spinal cord injury (SCI). While well-established methods such as von Frey mechanical and facial grimace testing are often used to assess SCI-induced NP-like behaviors in animal models, these assays have significant limitations, including experimenter bias and long periods of active testing and analysis. To address these challenges, we aimed to develop a novel open field 2-texture preference test (TTPT) to assess NP-like behaviors following unilateral C5 hemicontusion SCI in mice. To do so, we modified the open field apparatus by introducing both a rough and a smooth …

Templating Of Monomeric Alpha-Synuclein Results In Inflammation And Snpc Dopamine Neuron Death In A Genetic Mouse Model Of Induced Synucleinopathy, Matthew D. Byrne, Peyman Petramfar, Jae-Kyung Lee, Richard J. Smeyne

Department of Neuroscience Faculty Papers

While the etiology of most cases of Parkinson's disease (PD) are idiopathic, it has been estimated that 5-10% of PD arise from known genetic mutations. The first mutations described that leads to the development of an autosomal dominant form of PD are in the SNCA gene that codes for the protein alpha-synuclein (α-syn). α-syn is an abundant presynaptic protein that is natively disordered and whose function is still unclear. In PD, α-syn misfolds into multimeric b-pleated sheets that aggregate in neurons (Lewy Bodies/neurites) and spread throughout the neuraxis in a pattern that aligns with disease progression. Here, using IHC, HC, …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Environmental Exposures And Familial Background Alter The Induction Of Neuropathology And Inflammation After Sars-Cov-2 Infection, Debotri Chatterjee, Drishya Kurup, Richard Jay Smeyne

Department of Neuroscience Faculty Papers

Post-infection sequela of several viruses have been linked with Parkinson's disease (PD). Here, we investigated whether mice infected with SARS-CoV-2 alone or in combination with two putative Parkinsonian toxins, MPTP and paraquat, increased the susceptibility to develop Parkinsonian pathology. We also examined if G2019S LRRK2 mice had any change in sensitivity to SARS-CoV-2 as well as if vaccination against this virus altered any neuropathology. Infection with WA-1/2020 or Omicron B1.1.529 strains sensitized both WT and G2019S LRRK2 mice to the neuropathological effects of a subtoxic exposure to MPTP, but not paraquat. These neuropathologies were rescued in WT mice vaccinated with …

Changes In Brain Functional Connectivity Associated With Transcutaneous Auricular Vagus Nerve Stimulation In Healthy Controls, Daniel A. Monti, Nancy Wintering, Faezeh Vedaei, Alicia Steinmetz, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

PURPOSE: A growing number of research studies have explored the potential effects of vagus nerve stimulation (VNS) on brain physiology as well as clinical effects particularly related to stress and anxiety. However, there currently are limited studies showing functional changes during different frequencies of stimulation and laterality effects transcutaneous auricular VNS (TaVNS). In this study, we evaluated whether TaVNS alters functional connectivity in the brain of healthy controls. We hypothesized that TaVNS would significantly alter connectivity in areas involved with emotional processing and regulation including the limbic areas, insula, frontal lobe regions, and cerebellum.

METHODS: We enrolled 50 healthy controls. …

Does Body Mass Index Influence Intraoperative Costs And Operative Times For Open Transforaminal Lumbar Interbody Fusion? A Time-Driven Activity-Based Costing Analysis, Danyal A. Quraishi, Advith Sarikonda, Dwight M. Self, Emily Isch, Steven R. Glener, Arbaz A. Momin, Ashmal Sami, Nicholas Clark, Joshua Pelta-Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neuroscience Faculty Papers

BACKGROUND: The increasing prevalence of obesity has raised concerns about its impact on surgical outcomes and healthcare costs. This study evaluates the influence of Body Mass Index (BMI) on intraoperative costs and operative times during open Transforaminal Lumbar Interbody Fusion (TLIF) procedures using a Time-Driven Activity-Based Costing (TDABC) approach.

METHODS: A retrospective analysis was conducted on 279 patients who underwent TLIF between 2019 and 2022. Patients were categorized into 5 BMI cohorts: healthy weight (BMI 18.5-24.99), overweight (BMI 25.0-29.99), Class I obese (BMI 30.0-34.99), Class II obese (BMI 35.0-39.99), and Class III obese (BMI >40). Intraoperative costs were calculated using …

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

Ephrin-B2 Promotes Nociceptive Plasticity And Hyperalgesic Priming Through Ephb2-Mnk-Eif4e Signaling In Both Mice And Humans, Eric David, Muhammad Saad Yousuf, Hao-Ruei Mei, Ashita Jain, Sharada Krishnagiri, Hajira Elahi, Rupali Venkatesan, Kolluru Srikanth, Gregory Dussor, Matthew Dalva, Theodore Price

Department of Neuroscience Faculty Papers

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines …

Dopamine Release Neuroenergetics In Mouse Striatal Slices, Msema Msackyi, Yuanxin Chen, Wangchen Tsering, Ninghan Wang, Hui Zhang

Department of Neuroscience Faculty Papers

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater …

Icnirp Statement On Short Wavelength Light Exposure From Indoor Artificial Sources And Human Health, Sharon Miller, Christian Cajochen, Adele Green, John Hanifin, Anke Huss, Ken Karipidis, Sarah Loughran, Gunnhild Oftedal, John O'Hagan, David H Sliney, Rodney Croft, Eric Van Rongen, Nigel Cridland, Guglielmo D'Inzeo, Akimasa Hirata, Carmela Marino, Martin Röösli, Soichi Watanabe

Department of Neuroscience Faculty Papers

Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from …

Automated Seizure Detection Based On State-Space Model Identification, Zhuo Wang, Michael Sperling, Dale Wyeth, Allon Guez

Department of Neuroscience Faculty Papers

In this study, we developed a machine learning model for automated seizure detection using system identification techniques on EEG recordings. System identification builds mathematical models from a time series signal and uses a small number of parameters to represent the entirety of time domain signal epochs. Such parameters were used as features for the classifiers in our study. We analyzed 69 seizure and 55 non-seizure recordings and an additional 10 continuous recordings from Thomas Jefferson University Hospital, alongside a larger dataset from the CHB-MIT database. By dividing EEGs into epochs (1 s, 2 s, 5 s, and 10 s) and …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Emerging Perspectives Of Synaptic Biomarkers In Als And Ftd, Karthik Krishnamurthy, Raj Kumar Pradhan

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

Fundamental Neurochemistry Review: The Role Of Enteroendocrine Cells In Visceral Pain, Annie Londregan, Tyler D. Alexander, Manuel Covarrubias, Scott A. Waldman

Department of Neuroscience Faculty Papers

While visceral pain is commonly associated with disorders of the gut-brain axis, underlying mechanisms are not fully understood. Dorsal root ganglion (DRG) neurons innervate visceral structures and undergo hypersensitization in inflammatory models. The characterization of peripheral DRG neuron terminals is an active area of research, but recent work suggests that they communicate with enteroendocrine cells (EECs) in the gut. EECs sense stimuli in the intestinal lumen and communicate information to the brain through hormonal and electrical signaling. In that context, EECs are a target for developing therapeutics to treat visceral pain. Linaclotide is an FDA-approved treatment for chronic constipation that …

Profiles Of Resting State Functional Connectivity In Temporal Lobe Epilepsy Associated With Post-Laser Interstitial Thermal Therapy Seizure Outcomes And Semiologies, Mashaal Syed, Jingya Miao, Anish Sathe, Kichang Kang, Arichena Manmatharayan, Michael Kogan, Caio M. Matias, Ashwini Sharan, Mahdi Alizadeh

Farber Institute for Neuroscience Staff Papers and Presentations

Introduction: It is now understood that in focal epilepsy, impacted neural regions are not limited to the epileptogenic zone. As such, further investigation into the underlying functional connectivity (FC) patterns in those enduring Temporal Lobe Epilepsy (TLE) with Mesial Temporal Sclerosis (MTS) is imperative to understanding the intricacies of the disease.

Methods: The rsfMRIs of 17 healthy participants, 10 left-sided TLE-MTS patients with a pre-operative history of focal impaired awareness seizures (FIA), and 13 left-sided TLE-MTS patients with a pre-operative history of focal aware seizures (FA) were compared to determine the existence of distinct FC patterns with respect to seizure …

Maxsim: Multi-Angle-Crossing Structured Illumination Microscopy With Height-Controlled Mirror For 3d Topological Mapping Of Live Cells, Pedro Felipe Gardeazabal Rodriguez, Yigal Lilach, Abhijit Ambegaonkar, Teresa Vitali, Haani Jafri, Hae Won Sohn, Matthew B. Dalva, Susan Pierce, Inhee Chung

Department of Neuroscience Faculty Papers

Mapping 3D plasma membrane topology in live cells can bring unprecedented insights into cell biology. Widefield-based super-resolution methods such as 3D-structured illumination microscopy (3D-SIM) can achieve twice the axial ( ~ 300 nm) and lateral ( ~ 100 nm) resolution of widefield microscopy in real time in live cells. However, twice-resolution enhancement cannot sufficiently visualize nanoscale fine structures of the plasma membrane. Axial interferometry methods including fluorescence light interference contrast microscopy and its derivatives (e.g., scanning angle interference microscopy) can determine nanoscale axial locations of proteins on and near the plasma membrane. Thus, by combining super-resolution lateral imaging of 2D-SIM …

Dissecting The Daily Feeding Pattern: Peripheral Clock/Cycle Generate The Feeding/Fasting Episodes And Neuronal Molecular Clocks Synchronize Them, Akiko Maruko, Koichi M Iijima, Kanae Ando

Department of Neuroscience Faculty Papers

A 24-h rhythm of feeding behavior, or synchronized feeding/fasting episodes during the day, is crucial for survival. Internal clocks and light input regulate rhythmic behaviors, but how they generate feeding rhythms is not fully understood. Here we aimed to dissect the molecular pathways that generate daily feeding patterns. By measuring the semidiurnal amount of food ingested by single flies, we demonstrate that the generation of feeding rhythms under light:dark conditions requires quasimodo (qsm) but not molecular clocks. Under constant darkness, rhythmic feeding patterns consist of two components: CLOCK (CLK) in digestive/metabolic tissues generating feeding/fasting episodes, and the …

Synlight: A Bicistronic Strategy For Simultaneous Active Zone And Cell Labeling In The Drosophila Nervous System, Michael A. Aimino, Jesse Humenik, Michael J. Parisi, Juan Carlos Duhart, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

At synapses, chemical neurotransmission mediates the exchange of information between neurons, leading to complex movement, behaviors, and stimulus processing. The immense number and variety of neurons within the nervous system make discerning individual neuron populations difficult, necessitating the development of advanced neuronal labeling techniques. In Drosophila, Bruchpilot-Short and mCD8-GFP, which label presynaptic active zones and neuronal membranes, respectively, have been widely used to study synapse development and organization. This labeling is often achieved via the expression of 2 independent constructs by a single binary expression system, but expression can weaken when multiple transgenes are expressed by a single driver. Recent …

Absence Of Chordin-Like 1 Aids Motor Recovery In A Mouse Model Of Stroke, Eileen Collyer, Bridget R Boyle, Yolanda Gomez-Galvez, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that regulates synaptic maturation, and limits plasticity via GluA2-containing AMPA receptors (AMPARs). It was demonstrated that Chrdl1 expression is very heterogeneous throughout the brain, and it is enriched in astrocytes in cortical layers 2/3, with peak expression in the visual cortex at postnatal day 14. In response to ischemic stroke, Chrdl1 is upregulated during the acute and sub-acute phases in the peri-infarct region, potentially hindering recovery after stroke. Here, we used photothrombosis to model ischemic stroke in the motor cortex of adult male and female mice. In this study, we demonstrate that elimination …