Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as epilepsy and Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.

Intellectual Merit. The totipotent state exists during a brief period of embryonic development soon after fertilization before implantation. In contrast to pluripotent embryonic stem cells (ESCs) or reprogrammed iPSCs, which have the potential to generate all embryonic tissue types, totipotent cells can produce both embryonic and extraembryonic tissues. To date, the totipotent state can be achieved by natural fertilization, or artificially by somatic cell nuclear transfer (aka cloning) or removal of epigenetic regulators in iPSCs.

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.

Generalization, the tendency to respond in similar ways in different situations, can be adaptive or maladaptive, depending on the context. For example, generalizing fear of a real threat to other similar dangerous contexts can be important for survival; conversely, displaying fear in safe environments is detrimental. The ventral hippocampus (VH) is in a key position to modulate valence and provide contextual information that allows for selective or generalized responses. Yet little is known about how this area modulates these behaviors.

Genetic testing has greatly advanced diagnosis of early onset epilepsy. In spite of the expanding number of monogenetic disorders, such as epilepsy in patients with Aristaless-related homeobox gene (ARX) mutations, many of these rare diseases do not have a validated experimental model and thus suffer from limited understanding of the mechanisms of brain development and epileptogenesis. ARX is a transcription factor which is widely expressed in the developing and adult brain, skeletal muscle, pancreas, and testes.

The brain uses previous activity in order to adapt to an ever changing environment. This history

dependence adaptation takes place at all scales of organization of the nervous system. The objective of this theory

project is to develop a shared formalism that can be applied to multiple history dependent phenomena, from the

biochemical reactions that underlie synaptic plasticity, to the emergent patterns in complex neural networks. At

In the diabetic retina disruption of fractalkine (FKN) signaling induces fibrin(ogen) deposition, increased production of IL-1b by microglia, vascular and neuronal damage.  But, how FKN and its receptor, CX3CR1, regulate microglia activation and retinal pathology is unknown.  In humans, two single nucleotide polymorphisms in the CX3CR1 locus (hCX3CR1-I249/M280) that show defective binding to FKN, play a key role in inflammation during diabetes.  Notably, assessments of the effect of hCX3CR1-I249/M280 in an animal model revealed that expression of the vari

Bone fragility fractures are a major concern of health care of rapidly aging populations due to the high

risk of long-term disability and even mortality. Such fractures are not only due to loss of bone mineral density

(BMD), but also due to adverse changes at different structural hierarchies of bone, including ultrastructural

changes observed in bone disorders (e.g. osteogenesis imperfecta, mucopolysaccharidosis, and age-related

Mechanisms guiding the precise wiring of neural circuits promote the development of our brain and define the function of neural networks. This wiring process continues even in the adult nervous system; adult-born neurons are incorporated into existing circuits, and connections are repaired or reconfigured after injury. In the case of the peripheral taste system, rewiring after taste receptor cell turnover is a process that continues throughout life.