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.

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.

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.

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.

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

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.

B cell-depleting therapies using anti-CD20 monoclonal antibodies have been successful for the treatment of relapsing-remitting multiple sclerosis (RRMS); however, B cell-depletion showed incomplete efficacy for the treatment of autoantibody-mediated autoimmune conditions, including Systemic Lupus Erythematosus (SLE) and neuromyelitis optica (NMO), most likely because of the failure to eliminate autoantibody-producing long-lived plasma cells (PCs).

Basic Research

Our Phase 1 aim is to use the Rehabilitation Treatment Specification System (RTSS) to develop a streamlined version of the SCORE treatment protocol (Core-SCORE) through consultation with therapists who participated in the original SCORE study and subject matter experts. The Core-SCORE treatment protocol identified in Phase 1 will then be evaluated as part of a research study involving Service Member s and Veterans with mTBI in Phase 2 of the project.