EURON and THEME joint PhD meeting

34
EURON and THEME joint meeting 2011
Altered hippocampal network oscillations in ASAdeficient
mice
Christina Albus 1 , Matthias Eckhardt 2 , Volkmar Gieselmann 2 , Heinz Beck 1 , Thoralf
Opitz 1
1 Laboratory for Experimental Epileptology, Department of Epileptology, Bonn, Germany; 2 Institute of Biochemistry
and Molecular Biology, Bonn, Germany.
Arylsulfatase A (ASA) is a lysosomal enzyme catalyzing the degradation of
sulfatides. Mice deficient in ASA accumulate sulfatides in glial cells, microglia, and
neurons and show neuromotor deficits as well as mild behavioral disturbances. In
addition, invasive EEG recordings have revealed a marked cortical hyperexcitability,
with episodes of spontaneous epileptiform activity. The phenotypic abnormalities
have so far been mainly ascribed to the progressive demyelination and axonal
damage, but if sulfatide accumulation exerts direct effects on neuronal excitability
is so far unknown.
To address this question, we first examined excitability on the network level in
the hippocampal slice preparation. In the hippocampal CA1 and CA3 subfields,
spontaneous slow episodes of population activity were observed under conditions
of slightly increased excitability, termed sharp waves (SPW), but their incidence
was not different in ASA-deficient mice compared to littermate controls. However,
we observed a significantly higher fraction of SPWs with superimposed high
frequency oscillations in the CA3 subfield of ASA-deficient mice (termed sharpwave
ripples, SWRs). To address the cellular basis for increased SWRs, we have
used intracellular recordings to examine the functional properties of pyramidal
neurons in both the CA1 and CA3 subfields. We could not identify any systematic
changes in passive or active membrane properties in hippocampal principal cells
when comparing ASA-deficient mice to littermate control animals.
These results suggest that ASA deficiency causes a selectively increased propensity
to generate high frequency network activity within the subfield. Given the lack
of functional changes in principal neurons, we propose that changes in inhbitory
micronetworks may mediate the increase in high-frequency synchronized activity
in ASA-deficient mice.
Supported by the BMBF (Project LEUKONET)