Molecular Neurobiology
All of our behaviors, both simple and complex, are determined by the function of synapses between neurons in our central nervous system. Thus, an understanding of behavior requires knowledge of how synapses are made and how synapses function. Research conducted in the Molecular Neurobiology Program is aimed at understanding the mechanisms that lead to the generation of neural cells and their targets as well as the mechanisms that allow axons to project to their targets, form synapses and signal to one another.
These studies take advantage of invertebrates, such as Drosophila and C. elegans, that are amenable to genetic analysis and that facilitate the identification of genes required for cell fate determination and for axon guidance. Several groups use mice and mammalian cells grown in cell culture to study the complex inductive interactions between presynaptic and postsynaptic cells required for neural differentiation and synapse formation.
Administrative Assistants:
Dolly Chan, Katherine Moore
Understanding how signals are exchanged at neuromuscular synapses is fundamental to understanding the principles that govern the formation and maintenance of synapses. The discovery of genes critical for forming and maintaining neuromuscular synapses has not only provided insight into the normal mechanisms for synapse formation but also led to the identification of genes that are responsible for congenital myasthenia and for understanding how mutations in these genes lead to deficits in neuromuscular function. In addition, recent studies have identified the synaptic proteins recognized by autoantibodies responsible for myasthenia gravis, and these findings provide new insights into potential therapies. Our lab uses multiple approaches, including molecular genetics, biochemistry and structural biology to understand how neuromuscular synapses form during development and how synapses are maintained and stabilized in adults. Moreover, we study the causes for neuromuscular diseases, including congenital myasthenia, myasthenia gravis and ALS, and we are using this knowledge to devise therapeutic strategies for these diseases.
One of the most important features of the nervous system is its remarkable plasticity of synaptic connections throughout life.
While synaptic rearrangement is critical for memory formation and functional recovery after nerve injury, synaptic loss correlates
with cognitive decline in the elderly and plays pivotal roles in the pathogenesis of many neurodegenerative diseases. At present, very
little is known about how synaptic changes take place in living animals.
Using Green Fluorescent Protein (GFP) expressing transgenic mice and in vivo transcranial two-photon microscopy, we have been able
to image the same GFP-labled synapses over extended periods of time in both the central and peripheral nervous system. This ability to
follow individual neuronal synapses in vivo opens a direct window to study structural plasticity of synapses under normal and pathological
conditions. We are currently investigating experience-dependent synaptic change as well as synapse loss in the pathogenesis of Alzheimer's disease.
Our laboratory is interested in defining mechanisms of neurotrophin
signal transduction responsible for cell survival, apoptosis, and
changes in synaptic plasticity. The actions of neurotrophins, such as
NGF, are dictated by an unusual transduction system with two different
receptors, the Trk tyrosine kinase and the p75 neurotrophin receptor. We
have found that the two receptors collaborate to send a survival signal
under limiting concentrations of NGF. However, neurotrophins can also
induce a cell death signal. This presents a biological paradox, in which
life-death decisions in the nervous system are dependent upon the
expression and action of two receptors with distinctive signaling
mechanisms.
We are also studying the mechanisms that promote differentiation of
oligodendrocytes and Schwann cells. We have found that dramatic changes
in the levels of CDK2 kinase and the cell cycle inhibitor, p27,
accompany the growth arrest of oligodendrocyte precursor cells. We also
want to define neuronal signals responsible for glial cell
differentiation. The axonal signals that trigger myelination by
oligodendrocyte and Schwann cells will be approached by a combination of
molecular and cellular approaches. These lines of /research are directly
applicable to a number of neurodegenerative diseases, including
Alzheimer's and Lou Gehrig's disease, and disabling disorders, such as
spinal cord injury and multiple sclerosis.
We study the organization and plasticity of the mammalian cortex, and the circuits and molecular signals that control vocal communication, from the single neuron level to behavior.
Dr. Niels Ringstad joined the Molecular Neurobiology Program at the Skirball Institute and the Department of Cell Biology in September, 2009 as an Assistant Professor. Dr. Ri
ngstad is joining the NYULMC research community from the laboratory of Nobel Laureate Dr. H. Robert Horvitz in the Department of Biology at MIT. Dr. Ringstad studies the genetic basis for behavior. His postdoctoral studies uncovered circuits and mechanisms that regulate reproductive behavior in C. elegans and discov
ered ion channels that function as receptors for a number of biogenic amine neurotransmitters, including dopamine
We like the smell of french fries sizzling in a deep fryer when we are hungry, but the smell is not appealing when we are completely sated.
This phenomenon, that the valence of food odor is determined by the satiety state is observed in other organisms including fruit flies. Our
laboratory uses molecular genetic tools, behavioral assays, and calcium imaging and electrophysiology techniques to study how valence is
coded in the fly brain. This study would provide insight not only into the basic neurobiological mechanism, but it could also help to develop
new treatments for obesity.
