Rhythms are ubiquitous in the brain. For humans and all mammals,
rhythms drive patterns of movements for behaviors such as locomotion,
feeding, and breathing. How does the brain generate these motor
that are critical for the sustenance of homeostasis and life itself?
We examine this question in the respiratory neural center, which is
because the rhythm-generating cells and networks can be isolated in
reduced preparations from neonatal mice that remain rhythmically
vitro, and spontaneously produce inspiratory-related motor rhythms,
is advantageous from an experimental perspective.
At the network level, we used confocal and two-photon laser-scanning
microscopy to make unprecedented measurements of the population size
generating respiratory rhythm: an essential core of approximately 180
inspiratory neurons makeup the rhythmogenic respiratory kernel.
At the cellular level, we characterized a calcium-activated
cationic current (ICAN) in inspiratory neurons that underlies bursts
activity that are responsible for the inspiratory phase of the
cycle. Unlike many neurobiological systems that depend on
voltage-dependent mechanisms and intrinsic bursting, i.e., "pacemaker"
neurons, ICAN is evoked synaptically, via biochemical signaling
in the context of endogenous network function.
Combining these new insights, we assembled a mathematical model of the
network, which shows that respiratory rhythm is a form of biological
organized" behavior. Neurons interact according to simple rules but
possesses a blueprint for the collective behavior that results.
Studying a measurable behavior like breathing under controlled in
conditions enables us to elucidate general principles linking neurons
synapses to full-scale behaviors. This provides the necessary basis
treatment and prevention of breathing disorders and is generally
in understanding brain function.
SOME RECENT PUBLICATIONS
Pace RW, Mackay, DD, Feldman, JL, Del Negro, CA (2007) Role of
Sodium Current in Mouse PreB?tzinger Complex Neurons and Respiratory
Rhythm Generation. J Physiol, accepted pending revision.
Feldman JL, Del Negro CA (2006) Looking for inspiration: new
on respiratory rhythm. Nat Rev Neurosci 7:232-241.
Del Negro CA, Morgado-Valle C, Hayes JA, Mackay DD, Pace RW, Crowder
Feldman JL (2005) Sodium and calcium dependent pacemaker neurons and
respiratory rhythm generation. J Neurosci 25:446-453.
Del Negro CA, Morgado-Valle C, Feldman JL (2002) Respiratory rhythm:
emergent network property? Neuron 34:821-830.