Protein homeostasis, or proteostasis, is essential for preserving all cellular functions and involves a balance of protein synthesis, folding, trafficking, and degradation. A collapse in proteostasis is a common feature of many neurodegenerative disorders that are characterized by the accumulation of insoluble protein aggregates in the brain. Parkinson’s disease (PD)...
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...