Nearly all animals exhibit behaviors that can be classified as sleep. The distinctly disadvantageous nature of the asleep state, evolutionarily speaking, accentuates its role as a critical physiological process, yet chronic inadequate sleep is prevalent in today’s society. Among the multitude of health problems that have been linked to chronic...
Basal ganglia are a highly interconnected group of nuclei involved in motor control. The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. While the prevailing basal ganglia circuit model assumes the GPe as merely a relay, phasic changes in the activity of GPe neurons during...
Approximately 80-90% of individuals with Parkinson’s disease (PD) develop motor speech impairments, predominantly in the form of voice dysfunction. It is known that the motor symptoms of PD arise from degeneration of the dopamine producing neurons in the substantia nigra and dysregulation of basal ganglia motor pathways. It is also...
Compromised protein homeostasis underlies accumulation of plaques and tangles in Alzheimer’s disease (AD); however, little is known about the early mechanisms that contribute to this process. To objectively assess protein turnover at early stages of amyloid beta (Aβ) proteotoxicity, we used dynamic metabolic labeling with stable isotopes followed by proteomic...
The hippocampus has a well-established role in episodic memory and serves as a hub in a network of distributed brain regions (i.e., hippocampal-cortical network; HCN). Theta-band (4-8 Hz) neural activity recorded in the hippocampus have been associated with memory processing, and synchronized theta oscillations among the hippocampus and HCN regions...
Neural stem and progenitor cell (NPC) fate specification is a crucial component of central nervous system development, and the myriad signaling pathways that guide it are poorly understood. In my thesis work, I aimed to elucidate signaling mechanisms of the bone morphogenetic protein family (BMP) and some of its targets...
Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a class of non-canonical, ganglion cell photoreceptors. These cells influence a variety of visual behaviors including contrast sensitivity, circadian photoentrainment, sleep, and even mood. These wide-ranging behavioral influences are attributed to the multiple subtypes (M1-6) that comprise the ipRGC population, with different...
We present two ways in which measures of information can be used for the design and analysis of neural networks in both the brain and the computer. In the brain, stimulus is often represented as a distributed pattern of activity in a network of neurons. The quality of such population...
Decisions in naturalistic environments usually feature delayed and uncertain outcomes that can only be reached after a sequence of actions are performed. For example, canonical stalking and pursuit strategies used by terrestrial predators often involve stages of concealment, pauses where the predator remains motionless, and high speed chase sequences. The...
Classical conditioning is a form of associative learning and can be used as a behavioral paradigm to model and investigate the neural mechanisms underlying associative learning. In this work, classical conditioning paradigms are used to test the effectiveness of a disease model on the impact of learning and emotional regulation...
Navigating through the world is typically a multisensory experience. Mammals are believed to navigate using a cognitive map of space stored in the hippocampus. Yet, it is unclear how and whether spatial information of different sensory modalities can contribute to this map. A major barrier to addressing this question has...
Movement and sensing fundamentally works in a synergistic manner. Animal's sensory organs --- be they independently movable like eyes or requiring whole body movement as in the case of electroreceptors --- are actively manipulated throughout stimulus-driven active sensing behaviors. Though these sensing-related motions have been individually reported and analyzed across...
A one-time, unilateral injury to the developing brain can interrupt the typical process of development and result in motor impairments that evolve over the course of the whole life-span. The timing of injury relative to neural development has implications for the continued refinement of the nervous system and the descending...
Research on how sleep contributes to memory has blossomed in recent years. These studies have generally focused on whether or not sleep impacts various types of memory independently. An open question is whether sleep interactively influences different memory types. My research focuses on two types of memory—specificity and generalization. Whereas...
The exchange of information in the brain is accomplished through sequences of action potentials that result from the integration of local microcircuits. Unraveling the connectivity of the neurons that constitute these microcircuits and how they contribute to network activity is vital for understanding how information is relayed through the brain...
In the vertebrate retina, neurons process visual signals, generating feature selectivity in their activity levels. We use computational models to understand these behaviors by interpreting them mathematically. One component of this analysis is the spatial selectivity or receptive field, a property found in all visual sensory neurons. The neurons found...
We present a biophysical model of GCaMP6f calcium fluorescence in CA1 pyramidal neuron dendrites based upon results from imaging and electrophysiology experiments. This work was completed using experimental results from the laboratory of Professor Daniel Dombeck, Department of Neurobiology. Constraining the model to reproduce different objectives --- from in-vitro and...
Understanding associative memory is fundamental for a variety of neurological and neurodegenerative diseases, however, a large proportion of this research has excluded female subjects due to unsubstantiated bias. By including intact females, ovariectomized females and males in the study of associative memory, clear sex differences in acquisition emerged. Female mice...
Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. Saccharomyces cerevisiae contains many endogenous prions – providing a powerful system to study prionization. Previously, the Li Lab demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion [SWI+]. A small region,...
Astrocytes are the most abundant cell type in the brain, yet the mechanisms involved in astrocyte differentiation and the level of astrocyte heterogeneity in the CNS, particularly in the human cortex, is largely unknown due to the lack of subtype-specific astrocyte markers and inaccessibility of human brain tissue. Here we...
Coiled-coil helix coiled-coil helix domain containing 10 (CHCHD10) is a nuclear gene that encodes for a mitochondria-enriched protein of unknown function. This type of protein is typically imported into mitochondria via the disulfide relay system which facilitates the formation of disulfide bridges between each coiled-coil helix, resulting in maintenance of...
Understanding associative memory is fundamental for a variety of neurological and neurodegenerative diseases, however, a large proportion of this research has excluded female subjects due to unsubstantiated bias. By including intact females, ovariectomized females and males in the study of associative memory, clear sex differences in acquisition emerged. Female mice...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron (MN) degeneration and resulting in progressive paralysis and death. ALS is genetically heterogeneous, disease pathophysiology is not completely understood, and there are no effective drug therapies. To develop broadly applicable therapeutics, we examine disease mechanisms in the...
Movement is achieved by combining synaptic inputs from various sources and activating motor unit populations. Motor units are the quantal elements of motor control which act as a neuromechanical transducer that converts sensory inputs into motor output. Because of the tight neuromuscular junctions between motoneuron axon terminals and a large...
Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. We used super-resolution and live-cell microscopy in human iPSC-derived neurons to demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons,...
Chemokines, such as Stromal Derived Factor 1 (SDF-1 or CXCL12) and their G protein coupled receptors (GPCRs) are well known regulators of the development and functions of numerous tissues. CXCL12 has two receptors: CXCR4 and CXCR7 or atypical chemokine receptor 3 (ACKR3). CXCR7 has been described as an atypical “biased”...
Coordinated movement relies on the precise and controlled activation of populations of motor units, which convert the commands of the nervous system into muscle forces. Motor unit firing patterns are often nonlinear and generated through the response to a combination of ionotropic excitatory and inhibitory commands, as well as metabotropic...
Processing of sensory information in the brain is a pervasive and fundamental phenomenon across animal species and is involved in both "hard-wired" innate responses as well as learned and adaptive behaviors. Here, I show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity and complex processing...
Inter-organelle contact sites have become increasingly appreciated as important regulators of cellular homeostasis, and disruption of inter-organelle contact site dynamics and function has been observed in various pathologies. Recently, inter-organelle contact sites between mitochondria and lysosomes were discovered, offering a new mechanism by which these two organelles may directly interact,...
Social engagement, or shared attention between a child and caregiver, is a critical process for language and social development. Although previous EEG studies have investigated child social processing in closely controlled, experimental studies, no study has examined the interactive, reciprocal process of naturalistic social engagement. In my first paper, we...
In memory overgeneralization, details from negatively-valenced episodic memories become excessively generalized to unrelated neutral situations. This is a key cognitive distortion associated with major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Stress promotes memory generalization, and this process likely relies on stress-induced changes in dorsal...
Stimulus generalization is a critical mechanism for facilitating behavioral flexibility. Generalization allows the brain to reduce computational demands that would otherwise be necessary to create unique representations for each and every encounter while allowing the ability to deal with the complexity of real-world situations. Stimulus generalization is a fundamental cognitive...
The dentate gyrus is the first region for information processing within the classic hippocampal trisynaptic circuit, and this position makes it an important structure for the formation of associative memories. The dentate gyrus contains two major types of excitatory neurons: granule cells and mossy cells. While previous work has shown...
Protein homeostasis, or proteostasis, is essential for preserving all cellular functions and involves a balance of protein synthesis, folding, trafficking, and degradation. A collapse in proteostasis is a common feature of many neurodegenerative disorders that are characterized by the accumulation of insoluble protein aggregates in the brain. Parkinson’s disease (PD)...
In the adult hippocampus of many mammalian species, populations of newborn dentate granule cells (DGCs) are continuously generated and undergo subsequent activity-dependent neuronal maturation and incorporation into the preexisting hippocampal circuitry. Increasing evidence has demonstrated that these young adult-born DGCs (abDGCs) participate in numerous cognitive and affective processes such as...
My research at northwestern with Dr. Christina Zelano focused on the human amygdala subnucleithat receive monosynaptic input from the olfactory bulb. Surprisingly little is known
about these brain regions, including their potential roles in olfactory and nonolfactory
processing. During my PhD, I completed three projects aimed at furthering our understanding...
Anxiety and depression are highly prevalent, recurrent, and major public health problems. Decades of research has uncovered associations between symptom dimensions of anxiety and depression and abnormal neural activation across executive control-, threat-, and reward-related networks. Recent studies have developed a hierarchical symptom structure of anxiety and depression termed the...
Background: The way in which one perceives their visual world (i.e., bottom-up visual perception) and what one pays attention to in their surroundings (i.e., top-down attention), are critical to uncovering underlying thoughts and cognitions, and impact how one operates in the social world. Individuals with autism spectrum disorder (ASD), a...
Herpes simplex virus (HSV) encephalitis (HSE) is the most common cause of sporadic fatal encephalitis, and despite targeted antiviral therapy, outcomes remain poor. While rare in adults, neonates are significantly more susceptible to severe HSV disease. Understanding both the host and viral factors that contribute to pathogenesis is critical to...
The retina does not act as a simple camera, rather visual information goes through multiple layers of processing before it reaches the brain. Retinal ganglion cells (RGCs) are the output neurons of the retina and process visual information in the retina and then project into the brain. There are over...
All animals purposefully navigate feature-rich environments: while exploring, in search of vital resources of food and water, finding mates, and patrolling and marking habitats. During these complex behaviors, continuous analogue input information from peripheral sensory organs guides discrete and digital sequential motor output; accordingly, each action is informed, modulated, or...
The cerebellar cortical system is an extensively studied circuit which is critical for motor learning. While multiple monoamines, such as norepinephrine and serotonin, modulate cerebellar cortical output, the mechanistic details of dopaminergic signaling in the cerebellum remain poorly understood. Additionally, neuronal cell types residing within the cerebellum remain relatively under-characterized....
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system tumor, characterized by resistance to therapeutic intervention, inevitable recurrence, and ultimately patient death. The dismal prognosis is due in part to underlying molecular factors that promote an intratumoral cellular state heterogeneity and protect tumor cells from cell death pathways....
Numerous insights into the sensorimotor systems that guide the control of voice have been garnered by observing how the system responds to manipulations of its auditory feedback. However, current approaches may be limited in the exploration of more complex parameters of volitional and adaptive voice control due to their limited...
Sensorimotor integration is a general term to describe how task-specific motor output is generated from the selective and rapid processing of sensory and motor information. The rodent vibrissal (whisker) system is an important model for the study of sensorimotor integration and active tactile sensing. This research uses the rodent vibrissal...
Electrical spinal cord stimulation is an emerging treatment for spinal cord injury that can improve walking and bladder control, among many other functions. While the anatomical location of the motor pools for muscles involved in locomotion in the lumbosacral cord has been identified, the map of the functional output of...
The current view in neuroscience holds that the brain, together with its sensory and motor structures and the environment, form a closed-loop system – a sensorimotor loop – in which the brain receives information from the environment and converts it into a motor response while simultaneously making predictions about future...
Affect represents a major domain of human consciousness, consisting of a complex group of psychophysiological processes to drive human behavior. Many genetic and environmental factors may cause dysregulation of affective states, resulting in disorders that severely disrupt normal cognitive function and diminish the quality of life. Transitions among affective states...
Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Despite the known sex differences in pain prevalence and perception, the precise nature of the mechanisms responsible for sexual dimorphism in chronic...
Persons with spinal cord injuries can use state-of-the-art brain-computer interfaces to control robotic arms. Despite this high-tech solution, their movements are slow and imprecise, much like those made by individuals who have lost proprioception, the sense of body position and movement. Intracortical microstimulation (ICMS) used to reactivate neural circuits in...