Modulation of motor programs to promote flexibility in rhythmic behaviors
Our lab has spent the past 20 years studying the cellular and synaptic mechanisms by which neuromodulators such as dopamine and serotonin can reconfigure small motor networks to generate variability in simple rhythmic behaviors. Our basic assumption is that relatively limited neural networks drive the muscle contractions that evoke simple repetitive behaviors. In order to allow these behaviors to be flexible rather than robotic, modulatory inputs alter the strengths of the synapses in the network, and also alter the intrinsic electrophysiological response properties of the component neurons. These actions essentially "rewire" the network in software, allowing a single anatomically defined network to generate a family of related behaviors. Our work is at the cellular and biophysical level, trying to understand how individual neurons and synapses are modulated. We use voltage clamp to study how single ionic currents are modulated, which alter the firing properties of network neurons and the release of transmitter from their terminals. We are also using molecular biological tools to modify the expression of ion channels and see how this modifies the network output. Finally, we have a long-term collaboration with Dr. John Guckenheimer (Mathematics, Cornell) to use the tools of dynamical systems analysis to study our oscillatory neural networks and generate models with significant predictive and explanatory power.
Spiny Lobster (Panulirus interruptus)
We study two major systems. The first is the 14-neuron pyloric network
in the lobster stomatogastric ganglion. This is perhaps the best understood
neural network at present; all of its neurons and their synaptic connections
are known. We have focused on the modulatory actions of three monoamines,
dopamine, serotonin and octopamine, and how each of them reconfigures
the simple 14-neuron network to generate a different rhythmic movement
of the pylorus in the lobster foregut. Our work has shown that network
reconfiguration is very complex, involving modulation of a large majority
of all possible connections and neurons. We have cloned a number of ion
channel genes from the lobster and are studying how overexpression of
these genes can modify the firing properties of the neurons. One gene,
shal, encodes a transient potassium current (A-type), but when overexpressed
in single pyloric neurons, it paradoxically does not alter their firing
properties. We discovered that this is due to a novel form of homeostasis
where an opposing current, the H-current, is upregulated at a constant
ratio to the increase in A-current, retaining the normal firing properties
of the neurons. The mechanisms underlying this mechanism are under investigation.
Mice
The second system is the mouse spinal cord network for locomotion. Fictive locomotion can be evoked in the isolated neonatal spinal cord by a combination of NMDA, serotonin and dopamine. We are studying how this comes about, with a major emphasis on studying how serotonin modifies the intrinsic firing properties of the network neurons. We are currently focusing on the commissural interneurons (CINs)the first identified members of the locomotor central pattern generator. Serotonin excites all CINs that are rhythmically active during fictive locomotion, and alters the properties of their action potentials. We have used calcium imaging and voltage clamp to show that serotonin reduces a calcium current in these neurons; this in turn might reduce a calcium-activated potassium current, exciting the neurons. This process is under current investigation.
Links of Interest
updated 9/15/06 - Suzanne Aceti Koehl
Additional Information
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