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...
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,...
To survive, animals, including human beings, have developed an amazing ability to learn the constantly changing environment. Specifically, detecting specific odorants in a noisy, variable background is crucial for finding food and water, mating, and avoiding potential dangers. For this purpose, rodents have developed an olfactory system that is powerful...
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...
Voltage-gated potassium (KV) currents play a crucial role in shaping and controlling the firing patterns that serve as the fundamental basis for the differential signal processing from the ear to the auditory cortex, with distinct firing patterns observed with high- and low-frequency phenotypes. This is an interesting phenomenon, in 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...
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...
The presence of subjective cognitive decline (SCD) among cognitively normal-for-age older adults is increasingly hypothesized to represent a preclinical stage in the development of Alzheimer’s dementia (Jessen et al., 2014). This project aimed to characterize this construct with regard to its cognitive, motor, emotional, and functional features. The first study...
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...
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...
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...
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...
SCN2A encodes the NaV1.2 voltage-gated sodium channel, which is thought to contribute to the development of the central nervous system. Pathogenic variants in SCN2A have been associated with neurodevelopmental disorders (NDD), including developmental and epileptic encephalopathies (DEE), intellectual disability (ID), and autism spectrum disorder (ASD). These disorders represent a significant...
One of the most fascinating observations in the brain is that the neural connections change with experience and this phenomenon is called synaptic plasticity. Patterns of activity or neuromodulators can acutely induce changes in the synaptic strength in the brain. My thesis is focused on understanding the mechanisms of plasticity...
The basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory circuit important for habit formation originating from the dorsolateral striatum (DLS). An exception to this parallel circuit organization was proposed to explain how information is...
Birds such as the barn owl and zebra finch are known for their remarkable hearing abilities that are critical for survival, communication and vocal learning functions. A key to achieving these hearing abilities is the speed and precision required for the temporal coding of sound; a process heavily dependent on...
Conversation is an important part of human life. Given globalization and the numerous languages around the world, it is increasingly likely that we will be communicating with others speaking in their second language (L2) rather than their first language (L1). In these situations, communication may require more effort. However, people...
Simple sensorimotor tasks, such as lifting a cup or balancing a tray, requires not only controlled motor output, but also the ability to accurately perceive sensory information. After a hemiparetic stroke, individuals often experience sensory deficits in addition to motor impairments. However, research on the extent of changes in sensory...
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...
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...