| MORPHOLOGIC CHANGES IN DENDRITIC STRUCTURE AND SPINE DENSITIES
MAY ACCOUNT FOR AGE-RELATED INCREASES IN ACTION POTENTIAL FIRING RATES
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| D.M.Kabaso1,3*; J.I.Luebke4; B.I.Henry5;
P.R.Hof2,3; S.L.Wearne1,2,3 |
| 1. Dept Biomath, 2. Dept Neurosci., 3. CNIC, Mount Sinai Sch
of Med, New York, NY, USA |
| 4. Dept. Psychiatry, Boston Univ., Boston, MA, USA |
| 5. Applied Math, UNSW, Sydney, Australia |
|
| Recent in vitro electrophysiological studies of neocortical
pyramidal neurons in monkey prefrontal cortex (PFC) show increased input
resistance and action potential (AP) firing rates with age. Using a variant
of 3D Sholl analysis, we characterized global neuronal mass distribution
(DM) in pyramidal neurons from macaque monkey PFC. DM
was decomposed into scaling exponents representing global dendritic tapering
(DT) and global branching (DN). The mass scaling exponent
was significantly larger with age (p<0.05), due primarily to a significant
decrease in global tapering with age (p<0.05). Proximal regions of the
apical trunk were also significantly thinner (p<0.05), and spine densities
significantly reduced with age. To determine the contribution of these age-related
morphologic changes to the observed electrophysiological changes, neurons
were electrophysiologically characterized, filled intracellularly with biocytin,
digitized in 3D, and simulated using compartment modeling. Model neurons
were constrained with recorded passive parameters. Ion channel conductances
and distributions were adjusted to fit the recorded AP data. To isolate
the effect of dendritic morphology, all other parameters were held constant
between modeled neurons. Without spines, the aged dendritic morphologies
produced significantly higher simulated AP firing rates (p<0.05). Addition
of spines to the compartment models further increased the age-related increase
in AP firing rates (p<0.01). We conclude that morphologic changes in
dendritic structure and spine densities can be a major determinant of increased
AP firing rates with age. Supported by ARC, NIH grants MH58911, MH60734,
DC05669, AG05138, AG00001, RR16754. |
Program No. 638.18
Poster presentation:Tuesday, Oct. 26, 9:00 AM - 10:00 AM
Location:T20 |
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