| Research
Interests
| Stress, Prefrontal Cortex, and Psychopathology |
| Stress has been hypothesized
to play a major role in several disorders, and the neurotransmitter
systems and brain structures that are altered by stress have
been implicated in a variety of psychological disorders. Thus,
assessment of the effects of stress on these neurotransmitter
systems and structures may have important implications for
the causes and prevention of these disorders. Prefrontal cortex
is a target for hormones involved in the stress response and
has been implicated in disorders such as schizophrenia and
depression that are exacerbated or precipitated by stress.
Thus, understanding the effects of stress on prefrontal cortex
is critical for understanding the influence of stress on psychopathology.
My lab is examining the effects of chronic stress and stress
hormones on behaviors mediated by prefrontal cortex, as well
as the changes in neural pharmacology and morphology that
underlie these effects. We have demonstrated that both chronic
stress and exposure to the stress hormone corticosterone reorganize
dendrites of neurons in prefrontal cortex. We are now beginning
to more fully characterize these effects, assess their functional
significance, and elucidate mechanisms underlying them. |
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Computer-assisted
reconstructions of Golgi-stained pyramidal neurons in
layer II-III of medial prefrontal cortex in an untreated
and a corticosterone-treated rat. Apical dendritic material
is increased proximal to the soma and decreased distal
to the soma. Right. Mean intersections of apical dendrites
with 10-mm concentric spheres summed across the proximal,
middle, and distal third of the arbor for untreated,
vehicle-, and corticosterone-treated rats. Vertical
bars represent S.E.M. values; asterisks (*) indicate
significant difference relative to untreated rats. |
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Computer-assisted
reconstructions of Golgi-stained neurons in layer II–III
of medial prefrontal cortex in unstressed (left) and
stressed (right) rats. Scale bar = 50 mm. These neurons
were selected because they are representative of apical
dendritic lengths above (top), near (middle), and below
(bottom) their respective group means. Right. Mean intersections
of apical (top) and basilar dendrites (bottom) with
10 mm concentric spheres in unstressed and stressed
rats. Data have been summed into 20 mm bins. Apical
dendritic material distal to the soma was reduced in
stressed rats, and the pattern of changes was similar
to that seen in corticosterone-treated rats. Vertical
bars represent SEM values. Asterisks (*) indicate significant
differences relative to unstressed rats. |
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| Age-Related Changes in Plasticity
of Frontal Cortex |
| Neural plasticity underlies a
variety of processes, including development, learning and
memory, and recovery from injury. Plasticity persists throughout
the lifespan, but evidence suggests that this plasticity may
be reduced in aging. For instance, the behavioral effects
of moderate head injuries are more pronounced in aged patients.
Similarly, aging prolongs the behavioral consequences of traumatic
brain injury in rats, and aged rats are differentially vulnerable
to the effects of loss of input to the hippocampus. These
differential responses to injury or lesion suggest that plasticity
is altered in the aged, which has important consequences for
both successful aging and treatment of neural disorders in
the elderly. I have used lesions of the nucleus basalis in
rats to assess neurochemical and morphological plasticity
in frontal cortex. This work has demonstrated altered plasticity
in frontal cortex of aging rats—lesions produce greater
dendritic atrophy and differential changes in the glutamatergic
system in aged rats. A current focus of the lab is to assess
the mechanisms that underlie age-related changes in plasticity
of frontal cortex and to determine how these changes influence
behaviors mediated by frontal cortex. In answering these questions,
I hope to contribute to our understanding of the basic mechanisms
of neural changes in aging, as well as the causes and treatment
of age-related dementias. |
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Computer-assisted
reconstruction of Golgi stained pyramidal neurons in
layer II-III of frontal cortex in sham (left) and 192IgG-saporin-lesioned
(right) young adult (top), middle-aged (middle), and
aged (bottom) rats. Scale bar = 100 mm. Right. Mean
basilar branch number (top) and length (bottom) ipsilateral
to sham and 192-IgG-saporin lesions of the NBM in young
adult, middle-aged and aged rats. Vertical bars represent
S.E.M. values; asterisks (*) indicate significant difference
relative to sham-lesioned, age-matched rats. Lesions
did not significantly alter the number or length of
basilar branches in young adult rats, but resulted in
significant atrophy of basilar branches in middle-aged
and aged rats. |
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Digital light
micrographs of dendritic spines on a second-order branch
in young adult sham-lesioned (top) and 192IgG-saporin-lesioned
rats (bottom). Right. Mean spine density on second-
(top), third- (middle), and fourth-order (bottom) basilar
branches ipsilateral to sham and 192IgG saporin lesions
of the NBM in young adult, middle-aged, and aged rats.
Vertical bars represent S.E.M. values; asterisks (*)
indicate significant difference relative to sham-lesioned
rats. NBM lesions significantly increased spine density
on second- and third-order branches in young adult but
not aging rats. |
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