Development
and hormonal regulation of neurons and neural circuits
People
in the Levine laboratory are united by a common interest in
the development and function of motor systems. We approach
questions of relevance to all nervous systems by exploiting
the powerful molecular and genetic tools that are available
in the insect, Drosophila, as well as the advantages afforded by larger insects for studies involving
electrophysiology.
During
metamorphosis, many of the neurons that participate in larval
behavior persist to become incorporated into the neuronal circuits
of the adult. To accommodate changes in behavior, these neurons
modify their dendritic structures, synaptic interactions, and
biophysical properties. One goal of the laboratory is to understand
the behavioral relevance of such changes by following the metamorphic
fates of identified neurons and the circuits in which they
are involved. For example, some motoneurons of the larva that
participate in crawling survive the degeneration of their target
muscles to innervate new adult muscles that participate in
walking behavior, whereas others persist to innervate new flight
muscles of the adult. In other cases, such as the neurons that
control adult heartbeat in Drosophila, novel circuits are formed. Structural modifications, such as the growth of
new dendrites and axonal ramifications, and functional changes,
such as alterations in membrane currents and synaptic connectivity
by the motoneurons, are linked to the development and production
of new behavior.
A
second goal is to characterize the molecular and cellular pathways
through which these developmental changes are regulated and
mediated. For example, we have shown that the steroid hormone,
20-hydroxyecdysone (20E) directs the reorganization of circuits
during metamorphosis by inducing the growth of new neuronal
processes and the formation of new synaptic connections that
are important for new components of behavior, thereby providing
a useful model for examining the basic mechanisms underlying
comparable steroid-mediated alterations in more complex nervous
systems. We are investigating the molecular pathways through
which steroid hormones and neuronal activity regulate dendritic
growth and ion channel expression through the use of mutant
and transgenic animals. A wide range of experimental approaches,
including intracellular and patch-clamp recording, confocal
microscopy and immunocytochemistry both in vivo and in cell culture, are used to address these fundamental questions. |
Selected
Recent Publications
Miller JE Levine RB. Oct 2006. Steroid hormone activation of wandering in the isolated nervous system of Manduca sexta. J Comp Physiol A Neuroethol Sens Neural Behav Phys, 192:1049-62
Dulcis D, Levine RB, Ewer J. Sep 2005. Role of the neuropeptide CCAP in Drosophila cardiac function. J Neurobiol, 64:259-74
Consoulas C, Levine RB, Restifo LL. May 2005. The steroid hormone-regulated gene Broad Complex is required for dendritic growth of motoneurons during metamorphosis of Drosophila. J Comp Neurol, 485:321-37
Dulcis D, Levine RB. Jan 2005. Glutamatergic innervation of the heart initiates retrograde contractions in adult Drosophila melanogaster. J Neurosci, 25:271-80
Dulcis D, Levine RB. Oct 2004. Remodeling of a larval skeletal muscle motoneuron to drive the posterior cardiac pacemaker in the adult moth, Manduca sexta. J Comp Neurol, 478:126-42
Dulcis D, Levine RB. Oct 2003. Innervation of the heart of the adult fruit fly, Drosophila melanogaster. J Comp Neurol, 465:560-78
Johnston RM, Levine RB. Oct 2002. Thoracic leg motoneurons in the isolated CNS of adult Manduca produce patterned activity in response to pilocarpine, which is distinct from that produced in larvae. Invert Neurosci, 4:175-92
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