We have a remarkable ability to perform complex, coordinated movements without much conscious effort. In addition to the computations required to generate commands for muscles, a key aspect of coordinated motor control is incorporating sensory feedback about the movement. One of the most important feedback routes is through proprioception, the...
After stroke, inappropriate muscle activity phasing during the locomotor cycle is a key contributor to locomotor impairment. Muscle phasing has been shown to vary between behaviors post-stroke, but the degree to which individuals can voluntarily modulate activity is unclear. This dissertation consists of a series of three studies that investigate...
The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous...
We perform many movements every day without much deliberation. However, moving can be seen as a form of decision-making since one of many possible movements must be selected and executed. The decision-making processes that underlie movements are influenced by various factors, including sensory perception, energetics, time, perceived rates of failure...
Identifying key molecular mechanisms and targets for therapeutic development in sporadic neurodegenerative diseases has been challenging. Therefore, in-depth investigation of genetic forms of disease can provide valuable insight into pathogenic disease mechanisms. The discovery of genetic forms of Parkinson’s disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative...
Recent studies have begun to examine white matter connectivity aberrations in psychiatric populations, such as major depressive disorder. Several studies have found reduced white matter integrity (WMI) in depressed samples, though the location of this reduction is not clear. Incorporating symptom measures of depression severity and rumination may allow for...
New neurons are continuously produced in the subgranular zone of the dentate gyrus of the hippocampus throughout life. These newborn dentate granule cells (DGCs) undergo a stereotyped process of morphological and functional maturation during the first few weeks after differentiation that recapitulates some aspects of postnatal neuronal development. The inhibitory...
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...