“The Role of the Delta Glutamate Receptors in the Nervous System”

Brain cells communicate when specialized proteins on their surface known as “receptors” sense specific chemicals and open channels in the membrane that allow charged particles to flow through, generating electrical current. One of these receptors, the delta glutamate receptor, has not been well characterized. Gantz demonstrated that these receptors are affected by the “fight-or-flight” chemical, noradrenaline, but this discovery left an open question regarding how the receptor was opening. Gantz and her team will continue working to improve understanding of delta glutamate receptor gating and ionic currents as well as the role of this receptor in remodeling connections between brain cells in response to experience. This is a necessary first step toward understanding how mutations identified in schizophrenia, major depressive disorder, and bipolar disorder affect delta glutamate receptor electrical current and the functional of neural circuits.

“Molecular identification of brainstem neurons that regulate bodily functions”

Geerling combines molecular neuroanatomy techniques with physiology and behavioral tests to identify neurons that control basic bodily functions, including appetite, bladder control, body temperature, and conscious wakefulness. Dysfunction of neurons controlling these functions can occur with age and often arises more quickly in the patients with neurodegenerative diseases. Each of these core bodily functions relies on a network of neurons spread throughout nervous system, but each network has a prominent concentration of neurons in a small region of the brainstem that includes the parabrachial nucleus. Geerling’s team produced the first genetic blueprint for distinguishing myriad populations of parabrachial nucleus neurons in 2022. Using this blueprint, they are mapping the connectivity between these neurons and the rest of the brain, and they have discovered and characterized neurons that control bladder function, salt appetite, and thermoregulation. Geerling’s most ambitious goal is to identify the subset of neurons in this region of the brainstem that is necessary for sustaining consciousness. Ultimately, his hope is that these brain-network maps will translate into clinically useful diagnostic and therapeutic advances.

Developmental Insights into Alzheimer Disease Pathogenesis
Marco Hefti, MD, focuses on the developmental role of the tau protein and its relation to neurodegenerative tauopathies in human postmortem brain tissue, with the goal of identifying novel tau-targeted therapeutics for Alzheimer disease and other neurodegenerative tauopathies. His work represents a novel approach to understanding the pathogenesis of Alzheimer disease and related neurodegenerative tauopathies as an aberrant reactivation of developmental pathways regulating tau phosphorylation and aggregation.

Targeting the neuroimmune response following traumatic brain injury
Elizabeth Newell, MD, seeks to identify molecular mechanisms of traumatic brain injury (TBI) that may be targeted through the development of novel, precision therapies. She investigates the mechanisms by which neuroinflammation contributes to secondary injury following TBI, with a focus on age- and cell-specific mechanisms. She has developed a novel pediatric rodent TBI model to facilitate the study of age-dependent effects of neuroinflammation following severe TBI. 

Understanding the amygdala’s role in controlling breathing
Brian Dlouhy, MD, seeks to understand the mechanisms behind breathing impairment during and after seizures, a critical risk factor for sudden unexpected death in epilepsy - the most common cause of death in patients with chronic refractory epilepsy. His previous work found that when seizure activity spreads to the amygdala, it can induce apnea and oxygen desaturation. Using both animal models and human epilepsy patients, his work seeks to identify individuals at risk for sudden unexpected death in epilepsy, define the amygdala-brainstem pathway that causes seizure induced loss of breathing, and develop new circuit-based interventions with already approved drugs or novel neurosurgical techniques.

Voltage-gated calcium channels in developmental models of neuropsychiatric disease
Aislinn Williams, MD, PhD, uses both animal and human models to study the mechanisms by which alterations in genes at the earliest stages of brain development increase risk for psychiatric disease, including bipolar disorder and schizophrenia. Her work aims to unravel how genes are changing during development and how these changes affect adult brain function. Identifying the developmental pathways involved in neuropsychiatric disease may lead to novel treatment targets.

Hanna Stevens, MD, PhD, studied how prenatal environmental factors, including maternal stress, environmental exposures, and genes affect early brain development, with the goal of understanding how these factors influence the risk of subsequent behavioral and psychiatric disorders.

Jan Wessel, PhD, investigated cognitive and motor control in health and disease with a view to understanding how motor and cognitive activity is optimally geared toward changing situational demands, and how age- and disease-related impairments to these functions can be alleviated.