Modulatory neurotransmitter systems profoundly influence circuit function and behavior with effects on processes ranging from learning and memory to the control of peripheral organ function. Developmental signals play critical roles in the establishment of normal adult function of these modulatory systems in both the central and peripheral nervous systems, and can also contribute to the progression of pathological states such as heart disease and developmental disorders.

We are interested in understanding the molecular and cellular interactions that direct the development of the noradrenergic and cholinergic systems, including those that innervate the heart and modulate cardiac function. We have identified neurotrophic factors and members of the bone morphogenetic protein family as regulators of a series of sequential and overlapping developmental events during sympathetic neuron development. These factors promote neurite growth, axonal arborization, and synapse formation, leading to functional maturation of sympathetic drive to heart cells. Neurotrophic and glial signals also modulate sympathetic synaptic transmission and co-transmission, suggesting a new role for local glial interactions within the mammalian sympathetic ganglia.

Cholinergic neurons in the central nervous system also provide modulatory control of target function through long-range projections to major brain areas involved in learning, emotion, and response to sensory information. We have shown that neurotrophin signaling within the basal forebrain contributes to the acquisition of cholinergic neurotransmitter properties and to the establishment of cholinergic innervation of cortical targets. These projections also modulate sensory behaviors and these interactions can be explored by using transgenic mice and other manipulations that perturb the level of cholinergic innervation and function.

Within these areas of interest, we use molecular, cellular, transgenic and electrophysiological approaches to investigate:

  1. The neurotrophic factors and glial-dependent pathways that drive developing noradrenergic and cholinergic neurons to acquire their unique neurotransmitter and synaptic properties;
  2. The reciprocal interactions between sympathetic neurons and their cardiac targets that lead to innervation and maturation of the heart and the mechanisms by which developmental changes affect mature properties and pathological processes, including hypertension;
  3. The development and function of cholinergic projections from the basal forebrain to the cortex and amygdala and the effects of cholinergic transmission on cortical circuits and behavior