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.
|Publication status||Published - 2008|
|Event||6th FENS Forum of European Neuroscience - Geneva, Switzerland|
Duration: 12 Jul 2008 → 16 Jul 2008
|Conference||6th FENS Forum of European Neuroscience|
|Period||12/07/08 → 16/07/08|