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...
Dynamic decision-making is a complex process that relies on our ability to generate, evaluate and implement a variety of strategies. Understanding how people navigate this process is a difficult problem that requires a wide range of methodologies. This study details a combination of behavioral experiments, computational modeling, and neuroimaging that...
Brain network organization, the emergence of cognition, and the accumulation of neurodegenerative pathology are interwoven concepts frequently studied under the umbrella of behavioral neurology, neuropsychiatry, neuropsychology, and neuropathology. One approach to studying the organization of cognitive processes is to study those with selective deficits in such networks. To understand how...
The basal ganglia are a remarkably complicated and interconnected tangle of subcortical nuclei whose exact function and composition are hotly debated to this day. What is plainly obvious, however, is that loss of dopaminergic modulation in the basal ganglia, as is the case in Parkinson’s disease (PD) following the progressive...
The mammalian retina contains three classes of photoreceptors: rods, cones and the recently discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs express the photopigment melanopsin and were initially thought to be a homogeneous population of cells that drive subconscious visual behaviors such as circadian photoentrainment and pupil constriction. However, recent...
Interactions between working memory and long term memory systems are still not well understood, as the systems have long been thought to be mostly separate. An interesting intersection of these memory systems is domain-specific expertise, whereby individuals are able to show supra-span memory for information related to the area of...
Voltage-gated Na channels are expressed in all neurons, and are responsible for the upstroke of the action potential. They are part of a complex of proteins that includes pore-forming α subunits and auxiliary subunits that modify their trafficking, gating, and function. The modulation of Na channels by auxiliary subunits is...
Background: Glioblastoma (GBM) tumors are the most malignant brain cancers and are characterized as Grade IV astrocytomas by the World Health Organization. GBM tumors can be classified into three molecular subtypes known as proneural, classical, and mesenchymal. In addition, GBM tumors also have a small population of cells known as...
In everyday conversation, individuals actively process speech in order to comprehend and respond in real-time. As a word unfolds, listeners activate possible lexical candidates and actively determine the target word as they receive more information, a process referred to as incremental processing. This process requires knowledge of one’s native spoken...
Episodic memory provides a means by which we reflect on the past, make decisions about the future, and form a learned identity. Episodic memory depends on the hippocampus as well as on the distributed set of regions that form a hippocampal-cortical network (HCN), including medial prefrontal, posterior cingulate, and medial...
In susceptible individuals, episodic memories of overwhelmingly stressful experiences can give rise to debilitating socio-affective symptoms, including social dysfunction. This occurs even when such memories are not easily accessed for retrieval. In this case, it is generally accepted that the restricted retrieval of such memories is due to their having...
The hippocampus has been identified as a critical structure for supporting spatial memory processes in both humans and animals alike. Many of these processes such as the ability to self-localize in a given environment as well as engage in goal-directed navigation are thought to depend on the location-specific firing of...