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Calabrese Lab Projects
Electrophysiology of HN cells
Network model of the leech heartbeat
timing network
Neuronal networks that produce rhythmic
motor patterns that underlie behaviors such as swimming in the
lamprey or the beating of crayfish swimmerets can be described
as chains of coupled segmental oscillators. In these systems,
progressive phase differences between segments are essential for
the generation of appropriate motor output. The neuronal network
that paces the heartbeat of the leech can also be viewed as a
chain of coupled oscillators, albeit with a length of only two
segments. In the leech there are two centers of oscillation in
the 3rd and 4th ganglion. These centers are coupled by coordinating
fibers which are the neuritic processes of heart interneurons
of the 1st and 2nd ganglia. Together these neurons form the timing
network that paces the heartbeat of the leech. We are studying
the intersegmental coordination of segmental oscillators in the
leech using a realistic neuronal network model. Individual neurons
are modeled as single compartments with Hodgkin and Huxley type
conductances. We are testing the idea that the observed 15% phase
lag between the segmental oscillators (the 4th ganglion leads
the 3rd) may be the result of inherent differences in the periods
of the segmental oscillators. We are also exploring the possibility
that asymmetries in the synaptic coupling between the oscillators
may affect their phase relationship.
Calcium imaging and fluorescent study
of HN cells
How does intracellular Ca concentration
correlate to spiking activity of HN cell? What is its contribution
into synaptic transmission? Does intracellular Ca regulate Ca
channels and other ion channels in HN cells? Which mechanisms
regulate Ca homeostasis/turnover in HN cells? What is the spatial
distribution of Ca channels and stores in the HN neuron? Where
in the neuron are Ca input and release initiated? Is there any
relation and coordination between extracellular Ca input and release
of Ca from intracellular stores? What is the spatial distribution
of the inhibitory synaptic connection between HN neurons? Is the
inhibitory synaptic connection monosynaptic or multisynaptic?
Is there a critical quantity of synapses which should be switched
on to maintain the reciprocal interaction of HN cells? To answer
these questions, we are observing HN cells filled with calcium-sensitive
dyes, and are studying effects of destroying small parts of HN
cells with focused light.
Anatomically realistic Modeling
How does the shape of an HN neuron contribute
to its behavior? How do different spatial distributions of ion
channels affect the cell's computation? Are these anatomical contributions
important to the HN network as a whole? To address these questions,
we are building anatomically realistic, multi-compartmental models
of HN cells.
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