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...
Stroke is the leading cause of permanent adult disability. Subcortical unilateral (hemiparetic) stroke affecting the internal capsule or basal ganglia is the most common of all strokes and usually results in hemiparesis of the contralateral arm and leg. About 80% of the individuals with a moderate to severe hemiparetic stroke...
Leptin, a peptide mainly secreted in proportion to adipose tissue mass, increases energy expenditure with a parallel increase in breathing. The existence of a leptin-mediated neural circuit linking breathing to metabolism has been speculated, yet the precise central mechanisms were unknown. In my thesis, I show that optogenetic activation of...
Mitochondrial complex I is the primary entry point for electrons into the mitochondrial electron transport chain that is composed of 45 individual protein subunits that are encoded in both the nuclear and mitochondrial genomes. Mitochondrial complex I sits at an important nexus in the essential bioenergetic, biosynthetic, and signaling functions...
Considerable progress has been made in characterizing the neural circuits that underlie stress, fear, feeding, and pain. However, little is known about how they affect each other. Stress bidirectionally regulates feeding, either increases (e.g., stress-induced binge eating) or decreases (e.g., stress-induced anorexia), depending on the types of stressors, duration of...
The interaction of amyloid-β (Aβ) with endogenous metal ions is thought to play a role in the pathogenesis of Alzheimer’s disease (AD). However, limited tools exist to study and modulate Aβ-metal binding. The Meade lab has developed cobalt(III) Schiff base (Co(III)-sb) complexes as protein inhibitors that competitively displace metals from...
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...