Expertise:
Patch
clamping, Brain slice technique, Intracellular/extracellular
recordings, neuronal network analysis
My laboratory focuses on the question how the brain controls
rhythmic activity. This issue is of great basic scientific
and clinical interest, because many mammalian neuronal networks
generate rhythmic activity, including networks within the
neocortex, basal ganglia, thalamus, locus coeruleus, the
hypothalamus, ventral tegmentum area, hippocampus, amygdala,
brainstem and spinal cord.
Throughout my research career I was interested in understanding
the neuronal basis of rhythmic activity. As a graduate student
and postdoctoral fellow I used invertebrate and vertebrate
model systems to unravel the neuronal basis underlying rhythmic
motor behaviors such as walking, flight and respiration.
At the University of Chicago I characterize functional neuronal
networks in functional brain slices to unravel more directly
mechanisms of mammalian rhythm generation. My laboratory
concentrates on three main projects.
(1) Brain slice techniques are used to unravel mechanisms
underlying the reconfiguration of the respiratory network
in response to aminergic and peptidergic neuromodulators
as well as hypoxia.
(2) More recently, we began to study neocortical and hippocampal
slices from mice to unravel rhythm generating mechanisms
and neuromodulation associated with neocortical and hippocampal
slow oscillations.
(3) In collaboration with the Department of Pediatrics
we use the slice technique to investigate rhythm generating
mechanisms underlying epilepsy in human cortex from children
with intractable epilepsy.
(4) Recently we began to study burst generation and modulation
in the Substantia nigra of mutant and wild type mice. This
study relates to mechanisms that underlie tremor generation
in Parkinson patients.
We established that the isolated respiratory network responds
to hypoxia in a biphasic manner, an augmentation is followed
by a depression and apnea. This response resembles qualitatively
the hypoxic response of the deafferented, but otherwise intact
respiratory network. Therefore the isolated respiratory network
can be used as an interesting model system to address clinically
relevant issues related to SIDS and other neurological disorders.
Of basic scientific interest was the quantitative characterization
of calcium currents in respiratory neurons. This study serves
as an important basis for a series of studies elucidating
the cellular mechanisms that lead to the hypoxic response.
In a team effort involving all members of my laboratory we
established a cascade of cellular events that can explain
how hypoxia leads to an initial augmentation (hyperventilation),
a secondary depression, apnea and the generation of gasping.
We demonstrated that the pre-Bötzinger complex, is responsible
for the generation of multiple respiratory states: eupnea,
sighs and gasps. We have also shown that the Pre-Bötzinger
complex is hypoxia-sensitive and that pacemaker neurons within
this area exhibit a similar frequency response to hypoxia
even when isolated from the respiratory network. The identification
of these hypoxia-sensitive pacemaker neurons lead to a series
of experiments that aim at unraveling the underlying hypoxia-sensitive
cellular mechanisms. More recently we began to study how
neuromodulators such as serotonin, substance P and norepinephrine
reconfigures the respiratory network in order to generate
different forms of respiratory patterns. The studies in the
neocortex and the substantia nigra are conceptually similar
and we examine how these networks reconfigure in response
to hypoxia and/or aminergic and peptidergic neuromodulators.
Specific research projects:
-- Rhythm generation in the mammalian respiratory network
-- Rhythm generation and epilepsy in neocortical networks
-- Burst generation in Substantia nigra
Laboratory personnel:
Dr. Jean-Charles Viemari, Postdoctoral Research Associate
jcv@uchicago.edu
Dr. Andrew A. Hill, Research Assistant Professor, Department
of Organismal Biology
Laavhill@yahoo.com
Dr. Atsushi Doi, Postdoctoral Research Associate
Doi@uchicago.edu
Michael Carroll, Graduate Student, Committee on Computational
Neuroscience
msc@uchicago.edu
William A. Thistlethwaite, (MD/PhD) Graduate Student, Committee
on Neurobiology
wthistle@uchicago.edu
Ana Mrejeru, Graduate Student, Committee on Neurobiology
ana1@uchicago.edu |
