A goal of modern neuroscience is to understand how genes
and their expression interact with neuronal network function
to produce complex behaviors. A unique strength of the NCBG
is its diverse faculty, who use a broad range of approaches
in multiple model systems. Three NCBG faculty, Susan
Nelson, Suzanne Paradis and Gina
Turrigiano, work on mammals - principally mice.
is interested in how embryonic precursor cells respond
to local environmental cues during the development of
the mammalian nervous system. She has focused on the restriction
of neural precursor cells to specific neuronal lineages
and the development and function of synaptic connections.
Birren has a special interest in neurotrophins as well
as neurotrophin receptors and their role in lineage restriction
as well as plasticity. She is also collaborating with
Sengupta (see below) and exploiting the complementary
strengths of the mouse and C. elegans systems to
study mutations in the Arx system, a conserved
genetic pathway that underlies several forms of human
mental retardation and autism.
is interested in the mammalian neocortex, neuronal anatomy,
circuitry and function. This brain region has an awesome
complexity of neuronal morphologies, and Nelson has recently
used microarray approaches to help define subtypes and
even suggest functional specialization. In addition, Nelson
shares an interest with Gina Turrigiano in Rett's Syndrome,
a major genetic cause of mental retardation. It is known
that this disease is caused by the loss of a transcriptional
repressor, and they study the physiological consequences
in a mouse model of Rett's Syndrome. Nelson and Turrigiano
also share an interest in cortical circuitry, physiology
and mechanisms of synaptic plasticity.
Suzanne Paradis focuses on the complex circuitry of the mammalian brain that enables the execution of fundamental cognitive processes such as learning, speech, and memory. Neural circuits are assembled via specialized sites of cell-cell contact and communication between neurons termed synapses. Aberrant synapse development can have pathological consequences for circuit function as demonstrated by the manifestation of devastating neurological impairments, including epilepsy and autism spectrum disorders. The aim of our research is to define the molecular program that underlies both excitatory and inhibitory synapse development with the goal of contributing to a greater understanding of neural circuit formation and function.
has an additional focus on the role of early environmental
influences on the development of cortical circuitry and
the plasticity mechanisms that underlie optimal cortical
development. Her lab is particularly focused on homeostatic
scaling, a phenomenon she proposed to deal with the daunting
problem of simultaneously maintaining flexibility and
stability of neuronal circuits. Birren, Nelson and Turrigiano
are also working on the sleep problem from several directions:
circuitry, physiology anatomy, and molecular biology,
e.g., what happens to gene expression in response to sleep
Four NCBG faculty, Paul
Rosbash and Piali
Sengupta exploit invertebrate model systems,
either the fruit fly Drosophila or the worm C.
elegans. Both models are widely used, because many genes
and processes central to the study of brain and behavior
are conserved between humans and these organisms; their
facile genetics and low cost are also appealing.
studies neuronal morphogenesis and circuit formation in
Drosophila. He is also interested in the molecular
basis of behavior, focusing on the molecules and circuits
controlling thermosensation and thermotaxis. The molecular
pathways that mediate thermosensory behavior in flies
are related to the pathways that mediate temperature sensation,
pain and inflammation in mammals, suggesting that a deeper
understanding of fly thermosensory behavior will lead
to insights of significance for human health.
shares similar interests and uses C. elegans to
study how sensory neurons, thermosensory as well as olfactory,
recognize environmental cues and how they elicit appropriate
changes in development and behavior. Developmental question
include how sensory complexity is generated, and behavioral
questions include how plasticity is regulated, which occurs
in part at the level of olfactory receptor gene expression.
More recent objects of study include the neural and molecular
correlates of thermosensation and thermal memory.
focuses on regulation of the neuronal circuits underlying
learning and memory using Drosophila. Much of the
work is centered around the role of calcium/calmodulin-dependent
proteins kinase II (CaMKII), an enzyme that is central
to memory formation in both invertebrates and mammals.
Griffith is also interested in the circuitry that underlies
sleep in flies. Although sleep was once considered to
be an exclusively vertebrate behavior, it is now widely
believed that invertebrates like Drosophila also
sleep, and many critical features of human sleep can be
studied in flies.
is also interested in fly sleep, which is an outgrowth
of his interest in circadian rhythms. The circadian clock
regulates a daily sleep cycle (alternating periods of
alertness and sleep), in flies as well as in humans. This
cycle is aberrant in mutant fly strains as well as in
certain human sleep disorders. Most if not all of the
key molecules that function to regulate circadian timekeeping
are identical between flies and humans, making this system
essential for understanding this problem.