Specifically, in AD, spa[al naviga[on skills exhibit a gradual deteriora[on. ⢠CA1 hippocampal subfield shows par[cular vulnerability to neurodegenera[ve triggers.
Assessing the place field formation capability of CA1 pyramidal models in Alzheimer’s Disease 1,2 1 Panagio.s Bozelos , Panayiota Poirazi 1. Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece 2. Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
Results
Introduc$on Spa$al Naviga$on Skills Deteriorate in Alzheimer’s Disease (AD) • A variety of cri.cal computa.onal tasks is thought to be affected in senile neurodegenera.ve diseases, in ways not thoroughly explored. • Specifically, in AD, spa.al naviga.on skills exhibit a gradual deteriora.on. • CA1 hippocampal subfield shows par.cular vulnerability to neurodegenera.ve triggers. • The dynamic interplay between various structural aberra.ons is consistently reported, however a systema.c, quan.ta.ve and qualita.ve, examina.on of the causa.ve parameter space is s.ll missing. Research Mo$ve
Control
Stratum Lacunosum-Moleculare
• In order to understand when and why the ini.al compensa.onal adjustments to disease are gradually overtaken by func.onal losses, there is a need for a novel approach that could offer clear insights.
Methods Remodeling CA1 Pyramidal Neuronal Reconstruc$ons in silico by Using REMOD • A systema.c approach was implemented for remodeling the dendri.c morphology of CA1 pyramidal 3D neuronal reconstruc.ons (Fig. 1). • The method was able to simulate dendri.c altera.ons observed experimentally in AD, based on sta.s.cal descrip.ons found in literature (Fig. 3). • Modified morphologies were exported for compartmental modeling experiments implemented within the NEURON simula.on environment.
Fig. 1: REMOD: A Tool for Analyzing and Remodeling the Dendri$c Architecture of Neural Cells.
Fig. 3: Gradual degenera3on of CA1 pyramidal SLM, SR, and SO terminal dendrites by 5 steps of 20% shrinkage of their respec3ve ini3al length.
Fig. 2: Grid-like input sources were simulated in Matlab as a func$on of path loca$on, providing $me-series spike events.
Simula$ng CA1 Place Fields • A virtual square space of 100 x 100 cm was created for virtual explora.on path mapping purposes. • 6 grid-like input sources were simulated in Matlab as a func.on of path loca.on (Solstad et al., 2006) (Fig. 2), thus providing the .me-series spike events of EC and CA3 afferents onto the apical stratum lacunosum-moleculare (SLM), apical stratum radiatum (SR), and basal stratum oriens (SO) dendrites, respec.vely. • CA1 pyramidal model electrophysiological ac.vity was recorded at the soma for a total dura.on of 10,000 ms simula.on .me and mapped on the course of the virtual explora.on path (Fig. 4). • The place field forma.on capability was assessed for 1 control case and 3 cases of neuro-degenera.on of the terminal apical (SLM, SR) and basal (SO) dendrites (Fig. 5).
Stratum Radiatum
Stratum Oriens
Fig. 4: CA1 pyramidal model electrophysiological ac3vity mapped on the virtual explora3on path.
Fig. 5: Quan3fica3on of the place field forma3on capability of the 4 cases of the CA1 pyramidal model neuro-degenera3on.
Discussion Preliminary results suggest that the dendri.c tree shrinkage can lead to spa.ally expanding and noisier place fields, presumably due to the higher cellular excitability, manifested through both higher firing rates and increased burs.ng. This could offer a viable explana.on for the spa.al naviga.on impairment, observed in AD cases.
Further exploita.on of the proposed manipula.on scheme could retrieve valuable, and yet unsuspected, qualita.ve and quan.ta.ve results, hence aiding the development of targeted interven.ons for the preven.on of AD’s cogni.ve decline.
Acknowledgments
This work was supported by the ERC Star.ng Grant 2012 (GA-311435) “dEMORY: Dissec.ng the role of dendrites in memory”.
