Homeostatic regulation of intrinsic excitability in hippocampal neurons: response to chronic depolarisation
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1
University of Edinburgh, United Kingdom
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2
Institute of Adaptive and Neural Computation, United Kingdom
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 invitro 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.
References
1. Abbott LF, Nelson SB (2000) Synaptic plasticity: taming the beast.
Nat Neurosci 3:1178-1183.
2. Desai NS, Rutherford LC, Turrigiano GG (1999) Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nat Neurosci 2:515-520.
3. Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5:97-107.
Conference:
Bernstein Symposium 2008, Munich, Germany, 8 Oct - 10 Oct, 2008.
Presentation Type:
Poster Presentation
Topic:
All Abstracts
Citation:
O'Leary
TS,
Van Rossum
MC and
Wyllie
D
(2008). Homeostatic regulation of intrinsic excitability in hippocampal neurons: response to chronic depolarisation.
Front. Comput. Neurosci.
Conference Abstract:
Bernstein Symposium 2008.
doi: 10.3389/conf.neuro.10.2008.01.099
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Received:
17 Nov 2008;
Published Online:
17 Nov 2008.
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Correspondence:
Tim S O'Leary, University of Edinburgh, Edinburgh, United Kingdom, s0453454@sms.ed.ac.uk