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...
Findings in both humans and animal models have associated the hippocampal theta oscillation with hippocampal memory function. In animal models, previous research supports that the theta oscillation contributes to memory via phase-dependent changes in hippocampal network connectivity, wherein memory encoding versus retrieval are optimized at different phases of the theta...
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,...
The retina detects light, processes the visual signal, and sends a complex set of parallel information channels to the brain via a functionally diverse set of retinal ganglion cells types. This manuscript examines these retinal ganglion cell types, the visual features they encode, and the computational mechanisms leading to their...
In mature neurons, postsynaptic NMDARs are segregated into two populations, synaptic and extrasynaptic NMDARs, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content (NMDAR-plasticity). Here, we identify the phosphorylation of the PDZ-ligand of...
Visual information plays a critical role in controlling movement. People use visual information to plan future actions and correct current actions through feedforward and feedback processes, respectively. We can gain insights into these visually guided motor control processes by quantifying where people look during movement and measuring how much they...
Many species of rodents rely on the set of exquisitely sensitive facial vibrissae (whiskers) to guide rich behaviors in which other senses are inadequate. Although whiskers are, like all hairs, inert strands of keratin, they provide the animal with a rich landscape of tactile information which is used to guide...
Contactin associated protein like 2 (CNTNAP2) has emerged as a prominent susceptibility gene implicated in multiple complex neurodevelopmental disorders, including autism spectrum disorders (ASD), intellectual disability (ID), and schizophrenia (SCZ). The presence of seizure comorbidity in many of these cases, as well as inhibitory neuron dysfunction in Cntnap2 knockout (KO)...
Over the course of disease progression, half of adults with type II diabetes also develop diabetic peripheral neuropathy (DPN), peripheral nerve damage precipitated by the downstream metabolic effects of hyperglycemia, insulin resistance, and dyslipidemia. This multifactorial pathogenesis of DPN leads to various structural and physiological changes within the nerve, ultimately...
Perturbations to the physiology or impairments in the formation of synapses within the cochlea, specifically the ribbon synapses, result in decreased sensitivity to auditory stimuli. In example, prolonged exposure to moderately intense auditory stimuli, like power tools, can result in the swelling of nerve terminals, retraction of the postsynaptic membrane,...
Motor planning is fundamental to the performance of everyday reaching movements. The influence of planning is not limited to voluntary movements but extends to involuntary movements initiated in response to sensory stimuli, such as postural perturbations applied to the arm. Stroke alters voluntary reaching and the involuntary response to perturbations,...
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...
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...
Involuntary motor activities such as spasms arise from hyperreflexia in about 70% of individuals with spinal cord injuries (SCI). Despite this prevalence and the negative impact on health and safety, it is unclear what determines the severity of the spasms that develop. This study investigated the impact of injury severity...
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 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...
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...
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...
Neurodegenerative diseases (NDs) commonly involve the accumulation and aggregation of neurotoxic proteins that impair and ultimately destroy specific neurons. Considerable evidence from human and animal studies indicates that many NDs show disrupted circadian and sleep as symptoms. Yet little is known about the molecular mechanisms by which genes cause NDs...
Dystonia is a movement disorder characterized by involuntary and repetitive co-contractions of the agonist and antagonist muscles. Dystonia 6 (DYT6) is an autosomal dominant dystonia caused by loss of function mutations in the zinc finger transcription factor THAP1. I have generated Thap1 knock-out mice with a view to understanding its...
Spinal cord injury (SCI) is a devastating injury, which can be caused by motor vehicle accidents, violence, and non-traumatic causes. These injuries can leave patients with lifelong paralysis, as well as incontinence and life threatening autonomic dysreflexia. There is currently no FDA approved treatment for SCI. Spinal injury disrupts the...
Maneuvering your limbs requires both accurate commands for how to move, and accurate feedback of their true movements. Conventional prosthetic arms currently lack this sense of proprioceptive feedback, which can make daily tasks difficult without close visual monitoring. Although studies have successfully provided artificial proprioceptive feedback to improve control, this...
Individuals following a stroke suffer from a host of movement impairments that affect the upper extremity. Hand use is often significantly compromised, especially in individuals with more severe impairments, which makes it difficult for individuals to participate in activities of daily living. One of the major goals of rehabilitation is...
Our sense of smell, or olfaction, is one of our most evolutionarily ancient senses. In vertebrates, olfaction plays a crucial role in many functions, such as detecting and evaluating food, avoiding predators, regulating appetite, spatial navigation, and selecting mating partners. In addition, the olfactory system is highly dynamic and exhibits...
Findings in both humans and animal models have associated the hippocampal theta oscillation with hippocampal memory function. In animal models, previous research supports that the theta oscillation contributes to memory via phase-dependent changes in hippocampal network connectivity, wherein memory encoding versus retrieval are optimized at different phases of the theta...
Neurons are sensitive to the mechanical properties of their environment and show better growth, survival and differentiation when they are cultured in soft environments with mechanical properties similar to those of the brain compared to other tissues. Within the central nervous system (CNS), there is also a range of mechanical...
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...
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...
Aging is the greatest known risk factor for Alzheimer’s Disease (AD); however, the molecular mechanisms underlying aging and how it can initiate and or exacerbate AD, is still unknown. Epigenetic regulation has been widely accepted to play an essential role in aging or AD-related processes; however, whether dysregulations of histone...
Rhythmic fluctuations of electrical activity in the brain provide insights into the proposed mechanism by which we encode experiences and then maintain, forget, modify, and retrieve them. Yet there is still much to learn about how neural oscillations relate to memory function. The purpose of this research is to discover...
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...
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...
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...