Systems Neuroscience Commons^™

How To Search For The Engram: Optogenetics And Network Dynamics, Claudia Garcia Jou

Dissertations, Theses, and Capstone Projects

Memories are thought to be encoded by ensembles of neurons called "engram cells", because their artificial activation with optogenetics leads to the behavioral expression of a memory. However, the physiological mechanisms that mediate this process remain unknown. In this thesis, I investigate how optogenetic stimulation of memory-tagged cells changes neuronal firing, spatial coding, and the geometry of neural manifolds. I used an active place avoidance task and a foraging task to label engram cells in the dorsal hippocampus with Channelrhodopsin2 (ChR2). I then recorded the hippocampal activity response to optogenetic stimulation in mice under anesthesia, head-fixed, or freely moving. I …

Investigation Of Motor Neuronal And Circuit Level Mechanistic Determinants Of Spinal Excitability Following Cst Injury, Thelma Bethea

Dissertations, Theses, and Capstone Projects

The corticospinal tract (CST) is the primary descending motor pathway in mammals, essential for precise, dexterous movements, especially in humans and nonhuman primates. Damage to the CST, such as from spinal cord injury (SCI), impairs skilled motor function and triggers maladaptive changes including aberrant proprioceptive afferent sprouting and increased spinal excitability. These changes are closely linked to both muscle weakness and the development of hyperreflexia, compounding the functional deficits. Animal models of SCI are valuable for investigating mechanisms of injury and recovery, though traditional models often limit the ability to isolate circuit-specific contributions. To address this, I employed selective unilateral …

Parvalbumin Interneuron-Oligodendrocyte Interactions In The Infralimbic Cortex Promote Extracellular Plasticity Mechanisms After Safety Learning, Lucy Emma Denholtz

Dissertations, Theses, and Capstone Projects

The ability to differentiate between threat and safety cues is essential for adaptive behavior, yet this process is disrupted in psychiatric disorders, such as post-traumatic stress disorder (PTSD), where safety cues fail to downregulate fear expression. To better understand the neurobiological mechanisms of safety learning, I investigate how safety conditioning vs contextual fear conditioning modify behavioral and cellular mechanisms in the infralimbic (IL) region of the medial prefrontal cortex (mPFC) at several time points after learning. Through this work, I identify a novel mechanism whereby safety learning promotes learning dependent neuro-glial interactions that promote conditions for plasticity in the mPFC. …

Memory Interference In The Lateral Entorhinal Cortex, Omar Ghazy

Dissertations, Theses, and Capstone Projects

Memory interference occurs when previously formed memories disrupt the acquisition or retrieval of new information. A prominent example of proactive interference is latent inhibition (LI), defined as a reduced ability to form or express Pavlovian associations with a stimulus following non-reinforced exposure. The interference-based model suggests that LI arises because the memory that the pre-exposed stimulus is inconsequential interferes with the memory that it predicts a reinforcer.

Because interference increases with age, identifying its neural basis may help prevent or slow cognitive decline. Prior studies using the LI paradigm implicate the entorhinal cortex (EC) in retrieving the memory that a …

Neural Mechanisms Of Context-Sensitive Behavior In The Adult Male Zebra Finch, Katherine L. Anderson

Dissertations, Theses, and Capstone Projects

Adapting behaviors to the perceived external environment is key to the success and survival of individuals in social species. This context-sensitive modulation of behavior is critical for informative interactions with conspecifics, like alerting a neighbor to a nearing predator or capturing the attention of a potential mate. For the adult male zebra finch (Taeniopygia guttata), a vocal-learning songbird, context-sensitive adaptions to a learned song are key for developing and maintaining pair-bonds with females who are extremely attentive to subtle modulations of song structure. In this thesis, I explore the hypothesis that the influence of a social behavior network …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano

Dissertations, Theses, and Capstone Projects

Since the 1960s, neuroscientists have worked on the problem of estimating synaptic properties, such as connectivity and strength, from simultaneously recorded spike trains. Recent years have seen renewed interest in the problem coinciding with rapid advances in experimental technologies, including an approximate exponential increase in the number of neurons that can be recorded in parallel and perturbation techniques such as optogenetics that can be used to calibrate and validate causal hypotheses about functional connectivity. This thesis presents a mathematical examination of synaptic inference from two perspectives: (1) using in vivo data and biophysical models, we ask in what cases the …

Quantifying Psychostimulant-Induced Sensitization Effects On Dopamine And Acetylcholine Release Across Different Timescales, Georg Lange

Dissertations, Theses, and Capstone Projects

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of …

Ultrastructural Correlates Of Axons And Synapses Belonging To Different Circuits In Ferret Primary Visual Cortex, Anjelique Sawh

Dissertations and Theses

The goal of this study was to determine differences in distinctive layers of mammalian primary visual cortex through analysis of their ultrastructural characteristics. Characterizing brain circuitry using 3-dimensional reconstruction of electron microscopy images, and subsequent ultrastructural analysis of axonal populations provides us with a better understanding of the connectivity of the neural circuits. By quantifying ultrastructural differences in axonal processes such as synaptic densities, types of synapses and their post-synaptic densities (PSDs), mitochondrial volumes, synaptic vesicle aggregates, dendritic targets, and bouton volumes, we aimed to understand whether differences in anatomical specializations among different cortical layers could underlie differences in function …

The Effects Of False Heartbeat Feedback On Moral Judgment, Scott Koenig

Dissertations, Theses, and Capstone Projects

Research on human morality is at a crossroads, with one side claiming that moral judgment is the result of rational inference and the other side claiming that it is the result of emotion-laden intuition. This study investigated whether emotion drives moral judgment by manipulating a core component of the experience of emotion: physiological arousal. The sample consisted of 77 undergraduate students at Brooklyn College (57% women, 43% men; mean age = 20.1). One group of participants was led to believe their heart was beating quickly, and another group slowly, while they read and evaluated a series of text vignettes depicting …

Neural Processing Of Semantic Content In Movies, Maximilian Nentwich

Dissertations and Theses

Naturalistic stimuli, such as movies, contain interacting, multimodal and semantic features and allow for free exploration through eye movements. The full extent of neural responses to features such as motion, film cuts and eye movement behavior has not been established. The main hypothesis of this thesis is that complex multimodal and semantic stimuli in naturalistic movies engage a widespread ensemble of locations across the entire brain. To address this question I analyzed simultaneous intracranial and eyetracking data from over 6,000 electrodes across 23 patients with intractable epilepsy. Responses to fast eye movements – saccades – and film cuts are widespread …

Analysis Of Transplantable Photoreceptor Replacement Cell Chemotactic Mechanisms In Retinal Biomimetic Ligand Gradients, Onyekwere Onwumere

Dissertations, Theses, and Capstone Projects

Disease or trauma induced loss of rod and cone photoreceptors is a major cause of vision loss worldwide. To replace lost photoreceptors and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal injection of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). A major obstacle in the field is that transplanted photoreceptor replacement cells exhibit extremely limited migration into host retina following injection into the subretinal space. In this work, we show that PPCs and host retinal interaction bioinformatics modeling can identify key pathways involved in photoreceptor replacement cell migration and invasion behaviors. In addition, …

Neuroplasticity Of The Corticospinal System: Applications Of Neuromodulation-Based Therapies, Alzahraa M. Amer

Dissertations, Theses, and Capstone Projects

The motor cortex and corticospinal tract are necessary for producing skilled movements. I use intermittent theta burst stimulation (iTBS), a high-frequency stimulation protocol known to promote neural plasticity, as a tool to characterize short- and long-term plasticity of the CS system.

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced motor evoked potentials (MEPs), the effects produced by the corticospinal (CS) projection on spinal cord neurons have not yet been thoroughly studied. In Chapter 2, I determined if the CS tract (CST) is capable of producing LTP …

Rehabilitative Movement Approaches And Dance Interventions In Parkinson’S Disease, Cecilia Fontanesi

Dissertations, Theses, and Capstone Projects

The scope of this work is to address the functional deficits and symptoms experienced by those living with Parkinson’s Disease through movement interventions.

Chapter 1 offers a brief overview of current pharmacotherapy and rehabilitation approaches in Parkinson’s, focusing on dance in particular as a movement intervention that may be particularly suited to this population.

Chapter 2 focuses on brain plasticity and motor learning in PD, reporting the effects of rTMS applied after the acquisition of a motor skill. In this study, adaptation tested in patients with PD was comparable in the sham and TMS sessions, while retention indices tested on …

Sensory Perception, Adrian Rodriguez-Contreras

Open Educational Resources

Different types of sensory systems with their functional modalities will be presented. The biological bases for how these functions are generated and modified will then be described. Scientific information will be integrated into the lectures, such that students use critical skills in interpreting data, proposing hypotheses and designing experiments.

Experience-Dependent Changes In Nucleus Accumbens Activity Predict Cued Approach Learning: Contribution Of Nmda Receptors, Mercedes Vega Villar

Dissertations, Theses, and Capstone Projects

Animals learn associations between environmental cues and the natural rewards they predict (e.g., food, water, sex). As a result, reward-predictive cues come to trigger vigorous reward-seeking responses. Many neurons in the nucleus accumbens (NAc) become excited upon presentation of an already-learned reward-predictive cue. These NAc responses encode the motivational value of the cue and are necessary for the expression of the subsequent approach behavior. However, the precise temporal relationship between the emergence of cue-evoked excitations in the NAc and the acquisition of cued approach behavior remains unknown. In Experiment 1, NAc activity was recorded as rats learned to approach a …

Mechanisms Of Value-Biased Prioritization In Fast Sensorimotor Decision Making, Kivilcim Afacan-Seref

Dissertations and Theses

In dynamic environments, split-second sensorimotor decisions must be prioritized according to potential payoffs to maximize overall rewards. The impact of relative value on deliberative perceptual judgments has been examined extensively, but relatively little is known about value-biasing mechanisms in the common situation where physical evidence is strong but the time to act is severely limited. This research examines the behavioral and electrophysiological indices of how value biases split-second perceptual decisions and the possible mechanisms underlying the process. In prominent decision models, a noisy but statistically stationary representation of sensory evidence is integrated over time to an action-triggering bound, and value-biases …

Lateralized Temporal Integration Properties Of The Mouse Auditory Cortex, Demetrios Neophytou

Dissertations and Theses

Social communication calls are fleeting, rapidly modulating signals and the ability of the auditory system to perceive such transient signals is a remarkable phenomenon. The mechanism by which the auditory cortex (ACx) is believed to be capable of processing these signals is through recurrent connectivity in the cortical circuits. Recurrent connectivity is proposed to be a possible circuit motif that aids in the processing of these transient signals. Recurrent connectivity is believed to have an effect on the temporal fidelity, the ability to follow a modulating signal, and the recurrent activity, sustained activity following stimulus offset, at the level of …

Structure And Function Of Dopamine In The Inner Ear And Auditory Efferent System Of A Vocal Fish, Jonathan T. Perelmuter

Dissertations, Theses, and Capstone Projects

The neuromodulator dopamine is considered essential for coordinating the internal motivational state of an organism with appropriate behavioral responses to stimuli in the external environment. This could be accomplished by modifying the function of neural circuits involved in sensory processing such that they are “tuned in” and optimally sensitive to important stimuli during critical time windows. While dopamine modulation of auditory processing has been studied in the central nervous system, neuromodulation can also occur outside the brain, in the inner ear. The majority of investigations of dopamine in the ear are conducted using rodents and focus on its role in …

Sensory Perception, Adrian Rodriguez-Contreras

Open Educational Resources

Different types of sensory systems with their functional modalities will be presented. The biological bases for how these functions are generated and modified will then be described. As vision is the principal means of perception, we will focus in this course most on visual processing. Scientific data will be integrated into the lectures, such that students develop critical skills in analyzing data and proposing hypotheses.

Interhemispheric Communication And Lateralization In The Mouse Hippocampus, Jake Jordan

Dissertations, Theses, and Capstone Projects

The hippocampus is essential for memory and spatial navigation. Many theories have been proposed to explain how the hippocampus contributes to cognition; however, none has fully explained relevant neurophysiological and behavioral data. Hemispheric lateralization of hippocampal function has been reported in humans and in rodents, and lateralization of hippocampal neural circuitry has been reported in rodents. Most theories of hippocampal function fail to consider the hippocampus as a bilateral structure with hemispheric differences. Further, proposed theories of hippocampal lateralization have their own limitations in explaining empirical data concerning left/right function. Little is known about communication between the hippocampi across hemispheres. …

Influence Of Stimulus Intensity On Multimodal Integration In The Startle Escape System Of Goldfish, Camille Mcintyre, Thomas Preuss

Publications and Research

Processing of multimodal information is essential for an organism to respond to environmental events. However, how multimodal integration in neurons translates into behavior is far from clear. Here, we investigate integration of biologically relevant visual and auditory information in the goldfish startle escape system in which paired Mauthner-cells (M-cells) initiate the behavior. Sound pips and visual looms as well as multimodal combinations of these stimuli were tested for their effectiveness of evoking the startle response. Results showed that adding a low intensity sound early during a visual loom (low visual effectiveness) produced a supralinear increase in startle responsiveness as compared …

Contextually Modulated Avoidance Behavior In Rats Post-Pavlovian Extinction, Lauren Branigan

Theses and Dissertations

The following study sought to examine the psychological substrates of renewal (e.g.., context dependent extinction processes) for conditioned avoidance behaviors in rats. Using signaled active avoidance conditioning, rats acquired two-way shuttle responding, to two different auditory stimuli. These behaviors were then extinguished through exposure to the auditory stimuli where shuttling behavior was now without consequence. Subjects were then tested for renewal of avoidance in three distinct renewal sequences (e.g., ABA vs ABB, AAB vs AAA, and ABC vs ABB) in three separate groups of rats. It was found that subjects showed more responding to a stimulus presented outside of its …

Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson

Dissertations, Theses, and Capstone Projects

Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …

The Role Of Glutamate Neurotransmission In The Ventral Tegmental Area In The Expression Of Conditioned Approach Learning, Priscila Hachimine-Merli

Dissertations, Theses, and Capstone Projects

Conditioned stimuli (CSs) come to function as CSs by acquiring the capacity to activate the same mesocorticolimbic dopamine (DA) neurons activated by primary rewards, producing conditioned activation of these neurons and their associated motivational states. This model stipulates that CSs activate mesocorticolimbic DA systems through the activation of glutamate receptors on DA neurons in the ventral tegmental area (VTA). We tested the hypothesis that glutamate receptor stimulation in the VTA is necessary for the expression of conditioned approach. Rats were tested in a conditioned approach protocol that consisted of 7 consecutive conditioning sessions (light presentations and food were paired), one …

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present …

A Realization Of Modernity: Case Studies In Connectivity And Time, Mari Gorman

Dissertations, Theses, and Capstone Projects

My stated goal in applying to The Graduate Center was to explore my previous research in diverse fields of study. This research, the result of a formal investigation of acting, was and still is centrally focused on the subject of relationship itself, relationships being what actors create. In pursuit of a greater understanding of the essential nature of relationship in practical terms, a self-organizing complex system that constitutes universal relationship was unexpectedly discovered. As such, this system has been shown to offer solutions to many outstanding problems in diverse areas of study. The Liberal Studies program track, Approaches to Modernity …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

Rules And Mechanisms For Efficient Two-Stage Learning In Neural Circuits, Tiberiu Teşileanu, Bence Ölveczky, Vijay Balasubramanian

Publications and Research

Trial-and-error learning requires evaluating variable actions and reinforcing successful variants. In songbirds, vocal exploration is induced by LMAN, the output of a basal ganglia-related circuit that also contributes a corrective bias to the vocal output. This bias is gradually consolidated in RA, a motor cortex analogue downstream of LMAN. We develop a new model of such two-stage learning. Using stochastic gradient descent, we derive how the activity in ‘tutor’ circuits (e.g., LMAN) should match plasticity mechanisms in ‘student’ circuits (e.g., RA) to achieve efficient learning. We further describe a reinforcement learning framework through which the tutor can build its teaching …

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.