Molecular and Cellular Neuroscience Commons^™

Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To

Scripps Senior Theses

Autism Spectrum Disorder (ASD) refers to a heterogeneous neurological condition characterized by repetitive and restrictive behaviors and social communication deficits. ASD diagnoses are at a record high, at approximately 1 in 59 children according to the US Center for Disease Control. Currently, there are no available interventions that effectively treat the core symptoms of ASD. All pharmaceutical options address comorbid side effects of ASD but not core deficits and are particularly associated with negative side effects. Additionally, there are economic and geographic barriers that can prevent families of individuals with ASD from seeking or receiving effective interventions. Many of the …

M1 Melanopsin Ganglion Cells In The ​Mus Musculus​ Retina Are Similar In Shape And Size, Geoffrey K. Sarpong

Williams Honors College, Honors Research Projects

An M1 melanopsin retinal ganglion cell (mRGC) is a subtype of the five melanopsin ganglion cells. The M1-type mRGC is distributed on the dorsal retina of a mouse and has an extensively overlapping dendritic network in both the sublamina a (OFF) and sublamina b (ON) layers of the inner plexiform layer. In the dorsal retina, the M1-type mRGCs are distinct and asymmetric.

The aim of this study was to examine the morphological similarity (shape and size) of M1-type mRGCs. The study traced 20 neurons in the first four months of a glaucoma retina of a DBA mouse, made measurements of …

Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., Guela Sokhadze

Electronic Theses and Dissertations

Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or when …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Examining The Appropriate Recovery Interval Following Maximal Exertion For Baseline Computerized Neurocognitive Testing (Cnt), Samantha Mohler

Graduate Theses and Dissertations

Background: Computerized neurocognitive testing is part of the recommended multi-faceted approach to SRC assessment. Prior research has suggested that maximal exertion negatively effects CNT test scores. Purpose: To identify the appropriate timing of the administration of CNT following maximal exertion in healthy college-aged students. Study Design: Random cross-over, repeated measures design. Methods: Participants will be administered CNT on four different visits, with at least one week between administrations. A VO2 max treadmill test will be performed before CNT administration during three of the four trials. Following the VO2 max test, participants will rest for <2 minutes (immediate), 10-minutes, or 20-minutes before taking CNT. The fourth trial, without maximal exertion preceding CNT administration, will serve as the control. All trials will be randomly-counterbalanced to negate practice effects. RESULTS: There was a significant within-subjects effect for prescribed post-exertion recovery intervals on total symptom scores (Wilks λ = .62, F [3, 23] = 4.64, p = .01, η2= .38). Total symptom scores were significantly higher at the immediate (p < .002), 10-minutes (p = .018), and 20-minutes (p = .011) post-exertion recovery intervals compared to baseline. Additionally, a significantly positive within-subjects effect for prescribed post exertion recovery was observed for processing speed (p=.009, Wilks λ = .60, F [3, 27] = 5.9, η2 = .396). No significant effect was observed for visual memory (p = .07), verbal memory (p = .06), or reaction time (p = .40). CONCLUSION: Baseline symptom scores were negatively influenced processing speed was enhanced by maximal exertion. These changes continue to be elevated 20 minutes post-exertion. Moreover, cognitive performance was not significantly impaired following maximal exercise. To obtain more accurate baseline symptom scores, and allow processing speed composites to return to normal, sports medicine professionals should wait at least 20 minutes following maximal exertion before administering CNT.

Neonatal Stimulation Of Pkc Epsilon Signaling Normalizes Fragile X-Associated Deficits In Pvn Oxytocin Expression And Later-Life Social And Anxiety Behavior, Alexandra E. Marsillo

Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is an inherited developmental disorder characterized by disturbances in emotional and social behavior. Our studies have revealed suppressed hippocampal PKCε expression in Fmr1 knockout (KO) mice, the leading model of FXS. To compensate for this deficiency, we stimulated PKCε in neonatal KO mice by administering a selective PKCε activator, dicyclopropyl-linoleic acid (DCP-LA), and studied its effect on ventral hippocampal neurons and a proximal target of the ventral hippocampus, the hypothalamus, which regulates social and emotional behavior. We observed that at postnatal day 18 (P18), vehicle-treated KO mice displayed increased surface localization of the 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) …

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …

Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad

Dissertations, Masters Theses, Capstones, and Culminating Projects

An emerging technology known as three-dimensional (3D) tissue engineering has allowed scientists to mimic tissues found in vivo. Previous studies indicate that it is possible to differentiate dissociated mouse embryonic stem cells (mESCs) into 3D retinal tissues in vitro (Bertacchi, 2015; Eiraku, 2012). The newly differentiated retinal tissues are said to encompass all of the major components found in retinal tissues. The generation of in vitro 3D tissues holds great potential in terms of patient-specific disease modeling. Although various diseases have been well-studied in animal models, there are limitations with regards to patient-specificity. The generation of animal models to study …

Characterizing The Role Of Key Planar Cell Polarity Pathway Components In Axon Guidance, Grayland W. Godfrey Ii

Theses and Dissertations

An essential process to the development of the neural network of the nervous system is axon guidance. The noncanonical Wnt/Planar Cell Polarity pathway has been identified as an integral component in controlling the projection of axons during axon guidance. Prickle, ROR1 and ROR2 are PCP related proteins that do not have clearly defined roles in the process. This study aims to use zebrafish CoPA neurons as a model to study the roles of Prickle, ROR1, and ROR2 in axon guidance. Using in situ hybridization, morpholino knockdown, and CRISPR/Cas9 loss of function experiments were able to identify ror1, ror2 and …

The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, Michele Barry

Seton Hall University Dissertations and Theses (ETDs)

The inability to remember events experienced very early in life is referred to as Infantile Amnesia (IA) and has been observed in both humans and animals. Over the years interest in the phenomenon waned, but has recently increased with the discovery of new neurobiological methods to study brain function (e.g., Callaghan, Li & Richardson, 2014). The neurobiological mechanism behind IA has yet to be determined, but several innovative theories have been developed with these new research methods. The neurogenesis hypothesis theorizes that increased neurogenesis during early development disrupts previously established memories. The hippocampus, an area that mediates both the memory …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations & Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

Electronic Thesis and Dissertation Repository

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Pcdh19 Expression In Normal And Regenerating Adult Zebrafish Retinas, Kristin N. Forkapa Ms.

Williams Honors College, Honors Research Projects

My Honors Research Project will test the function of the N-cadherin molecule on the zebrafish optic nerve regeneration. N-cadherin is a member of the cadherin superfamily. Cadherins are cell adhesion molecules important for animal development and maintenance of adult structures. Unlike mammals, fish and amphibians have the ability to regenerate their optic nerve after damages. Molecular mechanisms underlying the optic nerve regeneration are still under intense investigation. Studies in Dr. Liu’s laboratory showed that expression of several cadherins, including N-cadherin, was greatly increased during adult zebrafish optic nerve regeneration, suggesting that cadherins may be involved in the optic nerve regeneration …

Investigation Of Mirnas Expression In A Citron-Kinase Mutant Model Of Microcephaly, Shan Parikh

Master's Theses

Mutation of Citron-Kinase (Cit-K) in rodents causes substantial reductions in the number of neurons generated in the CNS and results in a primary microcephaly-like phenotype. Evidence from drosophila genetics has further established a genetic link between Cit-K and a protein Argonaut 1 (AGO1), which is required for proper functioning of the miRNA machinery (2). Experiments characterizing the role of miRNAs in the developing cortex demonstrate the requirement of miRNAs for differentiation of neural progenitor cells starting at embryonic day 12.5 (3). Together, this evidence links the role of miRNAs to neurogenesis and thus this relationship warrants further investigation. Here miRNA …

Characterizing And Treating The Neuropathology Of Tuberous Sclerosis Complex In The Mouse, Sharon W. Way

Dissertations & Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting approximately 1 in 6000 births. Developmental brain abnormalities cause substantial morbidity and mortality and often lead to neurological disease including epilepsy, cognitive disabilities, and autism. TSC is caused by inactivating mutations in either TSC1 or TSC2, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in the development of these lesions is known. Murine models would greatly advance the study of this debilitating disorder. This thesis …

Developmental Changes In The Structure And Composition Of The Postsynaptic Density, Matthew T. Swulius

Dissertations & Theses (Open Access)

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed …