Martyn D. Goulding
Cell biology, University of Auckland, New Zealand
Ph.D., Cellular and Molecular Biology, University of Auckland
Postdoctoral fellow, Max Planck Institute for Biophysical Chemistry
The Goulding lab has a long-term interest in the development and functioning of neuronal circuits in the mammalian spinal cord. Our studies are centered on the spinal circuits that control locomotion and movement, protective reflexes and posture. Not only are these circuits important for movement disorders such as spinal cord injury and Parkinson's Disease, but they also provide neuroscientists with an ideal model system to explore how the nervous system generates complex behaviors. For this reason, we refer to these circuits as the "spinal brain". Studies in the lab use cutting edge genetic techniques, coupled with electrophysiology, circuit mapping, imaging and behavior to explore how the motor system works and how the spinal brain transforms sensory signals into discrete motor behaviors. Research in the lab is currently addressing: 1) The nature of the genetic programs that generate interneuron diversity in the spinal cord. 2) The identity and function of genetically-defined premotor interneurons that are core elements of motor networks in the spinal cord. 3) The structure and functional organization of sensorimotor circuits in the dorsal horn that process cutaneous sensory information.
"Studies in my lab are directed at understanding how
different types of spinal cord 'interneurons'—neurons
that bridge communications between sensory and motor
neurons—control how we move and how we respond to
touch and pain. Knowing more about how these cells
develop and function is a critical step in devising new
therapies to regenerate and activate circuits in the spinal
cord following injury."
Investigating how movement is controlled
lies at the center of our quest for understanding
how our nervous system works. We now
know that a hierarchy of "motor" networks
in the nervous system controls movements.
Among these are specialized networks of
interneurons in the spinal cord—commonly
referred to as central pattern generators
(CPGs)—that direct the rhythmic muscle
movements that underlie locomotion. These
spinal CPGs are engaged and controlled by
the brain to produce the coordinated muscle
movements that allow us to walk, talk and
play an instrument.
Although scientists have known about the
locomotor CPG for nearly 100 years, the
identity of the neurons that make up the
circuitry had remained a mystery. Goulding's
lab, in pioneering efforts to break the molecular
code that generates these different
interneuron cell types, has begun unraveling
the wiring of the spinal cord. Previously,
Goulding and his team discovered that a
subset of interneurons, called V0 neurons,
governs the left-right alternating pattern
of activity that is needed for stepping, as
opposed to hopping, movements. They have
also analyzed the function of other neurons,
including V1 neurons that set the pace at
which animals walk.
However, identifying the cells that control our
ability to flex and extend our limbs has proven
more difficult. These have an essential role in
movement, as without them we would not be
able to bend and stretch our arms and legs.
In a recent series of experiments, Goulding's
team identified a second class of inhibitory
neuron that cooperates with the V1 neurons
to control muscle activity that is needed to
move the limbs and walk. Strikingly, they
found that the same neurons are present
in the spinal cords of swimming vertebrates,
leading Goulding to propose that the "walking"
CPG is an evolutionary adaptation of
the "swimming" CPG circuit. More recently,
efforts in the lab have turned to understanding
how the spinal CPG is activated both by
touch and pain pathways that are important
for protective reflexes, and by descending
pathways from the brain–knowledge that is
essential for developing new treatments for
spinal cord injury.
Awards and Honors
- Pew Scholar, 1994-1998
- Basil O'Connor Research Award, 1993-1995
- Jacob Javits Neuroscience Investigator Award, 2006
Gross, M.K., Moran-Rivard, L., Velasquez, T., Nakatsu, M.N., Jagla, K., and Goulding, M.D. (2000). Lbx1 is required for muscle precursor migration along a lateral pathway into the limb. Development 127, 413-424.
Moran-Rivard, L., Kagawa, T., Saueressig, H., Gross, M.K., Burrill, J., and Goulding, M.D. (2001). Evx1 is a postmitotic determinant of V0 interneuron identity in the spinal cord. Neuron 29, 385-399.
Dottori, M., Gross, M.K., Labosky, P., and Goulding, M.D. (2001). The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate. Development 128, 4127-4138.
Gross, M.K., Dottori, M., and Goulding, M.D. (2002). Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34, 535-549.
Sapir, T., Geiman, E.J., Wang, Z., Velasquez, T., Mitsui, S., Yoshihara, Y., Frank, E., Alvarez, F.J., and Goulding, M. (2004). Pax6 and Engrailed 1 regulate two distinct aspects of Renshaw cell development. J. Neurosci. 24, 1255-1264.
Cheng, L., Arata, A., Mizuguchi, R., Qian, Y., Karunaratne, A., Gray, P.A., Arata, S., Shirasawa, S., Bouchard, M., Luo, P., Chen, C.L., Busslinger, M., Goulding, M., Onimaru, H., and Ma, Q. (2004). Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat. Neurosci. 7, 510-517.
Lanuza, G.M., Gosgnach, S., Pierani, A., Jessell, T.M., and Goulding, M. (2004). Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements. Neuron 42, 375-386.
Goulding, M., and Pfaff, S.L. (2005). Development of circuits that generate simple rhythmic behaviors in vertebrates. Curr. Opin. Neurobiol. 15, 14-20.
Kriks, S., Lanuza, G.M., Mizuguchi, R., Nakafuku, M., Goulding, M. (2005). Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord. Development 132, 2991-3002.
Gosgnach, S., Lanuza, G.M., Butt, S.J., Saueressig, H., Zhang, Y., Velasquez, T., Riethmacher, D., Callaway, E.M., Kiehn, O., Goulding, M. (2006). V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature 440, 215-219.
Mizuguchi, R., Kriks, S., Cordes, R., Gossler, A., Ma, Q., and Goulding, M. (2006). Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat. Neurosci. 9, 770-778.
Zhang, Y., Narayan, S., Geiman, E., Lanuza, G.M., Velasquez, T., Shanks, B., Akay, T., Dyck, J., Pearson, K., Gosgnach, S., Fan, C.M., and Goulding, M. (2008). V3 spinal neurons establish a robust and balanced locomotor rhythm during walking. Neuron 60, 84-96.
Goulding, M. (2009). Circuits controlling vertebrate locomotion: moving in a new direction. Nat Rev Neurosci. 10, 507-518.
Stam, F.J., Hendricks, T.J., Zhang, J., Geiman, E.J., Francius, C., Labosky, P.A., Clotman, F., Goulding, M. (2012) Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program. Development 139, 179-190.
Salk News Releases
- Salk scientists reveal circuitry of fundamental motor circuit, May 1, 2014
- Prestigious endowed chairs awarded to Salk scientists, March 30, 2012
- A fine balance, October 8, 2008
- Salk neurobiologist receives Javits Neuroscience Investigator Award, June 15, 2006
- Striking the right balance between excitation and inhibition, May 31, 2006
- Salk researchers make fast strides towards understanding how our body controls walking, March 14, 2006
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