Aniruddha Yadav

Christina M Weaver

D Kabaso

Jennifer I Luebke

Patrick R Hof

Yuan Z Gao

English

PubMed

Gao Yuan Z

Weaver Christina M

Yadav Aniruddha

Luebke Jennifer I

Hof Patrick R

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BMC Neuroscience

Age-related morphologic changes alter robustness of neuronal function

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POSTER PRESENTATION Open Access
Age-related morphologic changes alter
robustness of neuronal function
Aniruddha Yadav1,2*, Christina M Weaver3, Yuan Z Gao1,2, Jennifer I Luebke4, Patrick R Hof1,2
From Nineteenth Annual Computational Neuroscience Meeting: CNS*2010
San Antonio, TX, USA. 24-30 July 2010
Aging and neurodegenerative disorders significantly alter
both neuronal function and morphology. We have
shown recently that, if uncompensated by altered ion
channel distributions, morphologic changes in aging
increase neuronal excitability [1]. Different combinations
of active conductances can evoke similar firing patterns,
giving rise to functional homeostasis. To elucidate possi-
ble mechanisms of homeostasis in the parameter space
defined by ionic conductances, we recently utilized ther-
mal random walks to identify regions (an ensemble)
within which the functional output of a neuron is main-
tained. Typically a number of such regions, which are
topologically disconnected from each other, are identi-
fied. The eigenvalues and eigenvectors of the ensemble
covariance matrix serve as measures for its size and
orientation, and the capacity for functional homeostasis
or robustness is measured by the set of largest (robust)
eigenvalues and corresponding eigenvectors. In this
study, we explore how functional homeostasis might be
affected by the kinds of morphologic changes that occur
with aging or neurodegenerative disorders. To this end,
we extract the change in orientation and extent of the
ensembles found for the original model by subjecting it
to three kinds of perturbations involving morphology
and desired firing properties. First, we mimic age-related
morphologic degeneration by reducing the number of
spines in the original neuron. Second, we increase the
number of spines in the original neuron, mimicking a
younger one. The third perturbation also involves
increased spines, however, the target firing rate is
reduced so as to also mimic the electrophysiology of a
younger neuron. We find that, for all the perturbations
considered, the initial ensembles remain topologically
disconnected, although they change in size and orienta-
tion. In particular, while the sensitive eigendirections
remain unchanged, the robust eigendirections change in
orientation, suggesting that functional robustness of a
neuron is determined largely by its morphology. Conse-
quently, possible homeostatic mechanisms, that enable a
young neuron to maintain function, are able to do so
less efficiently as the neuron undergoes age related mor-
phologic changes .This is so because a homeostatic
mechanism would be more effective if it were to orient
itself along the robust eigendirections of the ensembles,
and become less so as the robust directions change due
to morphologic changes. Although morphologic pertur-
bations drastically change robust eigendirections, preli-
minary evidence indicates that these directions may be
restored through appropriate compensatory changes in
functional output. In conclusion, the need to maintain
functional robustness may be responsible for altered
function as a neuron ages.
Acknowledgements
Supported by NIH grants DC05669, NS13742 and MH071818.
Author details
1Department of Neuroscience, Mount Sinai School of Medicine, New York,
NY, USA. 2Computational Neurobiology and Imaging Center, Mount Sinai
School of Medicine, New York, NY, USA. 3Department of Mathematics and
Computer Science, Franklin & Marshall College, Lancaster, PA, USA.
4Department of Anatomy and Neurobiology, Boston University, Boston, MA,
USA.
Published: 20 July 2010
Reference
1. Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL: The electrotonic
structure of pyramidal neurons contributing to prefrontal cortical circuits
in macaque monkeys is significantly altered in aging. Cereb Cortex 2009,
19:2248-2268.
doi:10.1186/1471-2202-11-S1-P140
Cite this article as: Yadav et al.: Age-related morphologic changes alter
robustness of neuronal function. BMC Neuroscience 2010 11(Suppl 1):P140.
1Department of Neuroscience, Mount Sinai School of Medicine, New York,
NY, USA
Yadav et al. BMC Neuroscience 2010, 11(Suppl 1):P140
http://www.biomedcentral.com/1471-2202/11/S1/P140
© 2010 Yadav et al; licensee BioMed Central Ltd.


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1Department of Neuroscience, Mount Sinai School of Medicine,

Wearne SL: The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex

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Age-related morphologic changes alter robustness of neuronal function

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