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Homeostatic regulation of intrinsic excitability in hippocampal neurons: response to chronic depolarisation

Research output: Contribution to conferencePoster

Original languageEnglish
Publication statusPublished - 2008
Event6th FENS Forum of European Neuroscience - Geneva, Switzerland
Duration: 12 Jul 200816 Jul 2008


Conference6th FENS Forum of European Neuroscience


For the nervous system to function properly, activity levels must be regulated. The favourite candidate mechanism for learning and memory in the mammalian CNS is Hebbian learning – a process which tends to strengthen connectivity between excitatory cells in response to correlated firing patterns. In isolation, this constitutes a positive feedback loop, destabilising the average activity level in an intact network [1, 3]. It is therefore likely that homeostatic mechanisms exist to co-regulate activity on a cellular level, and several candidate mechanisms have been characterised to date [2, 3]. Here we describe an in-vitro model for homeostatic control of intrinsic excitability. We find that cultured hippocampal neurons respond to chronic depolarisation over a period of days by attenuating their response to injected current. Cells grown in depolarising medium containing 15 mM KCl exhibited a tenfold increase in the amount of steady current required to induce spiking (9.7+/-3.5 pA for n=25 control cells; 94.5+/-16.0 pA for n=18 treated cells). This effect was found to depend on the level of depolarisation and the length of treatment, and is accompanied by a decrease in voltage-gated sodium conductance in the cells. Consistent with these observations is a prominent hyperpolarising shift in resting membrane potential relative to control (-50+/-1 mV vs. -58+/-1 mV) and a drop in input resistance (790+/-140 MOhm vs. 330+/-60 MOhm). Using these data to parameterise a conductance-based computer model offered insight as to whether they could account for the observed differences in excitability.


6th FENS Forum of European Neuroscience


Geneva, Switzerland

Event: Conference

ID: 18572030