Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are two devastating neurodegenerative diseases that affect 100,000s of people globally. They have a severe adverse impact on society, yet there are currently no early diagnostic tools or disease-modifying therapies available. Despite their clinical heterogeneity, evidence points to these diseases being on...
The cerebellum is involved in sensorimotor processing and motor control in the brain. What has been found across many species for many behaviors is cerebellar Purkinje (Pkj) cells and cerebellar nuclear (CbN) cells show activity that is related to and predictive of movements. Less is known about how patterns of...
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...
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)...
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,...
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...
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...
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...
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...
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...
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...
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...
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...
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...