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Modulation of synaptically induced burst strength and spike onset timing by inactivating KIRcurrents in medium spiny neurons
BMC Neuroscience volume 9, Article number: P57 (2008)
The membrane potential of striatal medium spiny neurons (MSNs) fluctuates between down- and up-states. In ventral striatum, inward rectifying potassium (KIR) currents in 40% of MSNs inactivate . The significance of this property is not clearly known. We describe a computational study investigating how synaptic integration is influenced by KIR current inactivation.
Two MSNs were modeled using NEURON, one equipped with non-inactivating KIR currents (henceforth, "Cell A") and the other with inactivating KIR currents (henceforth "Cell B") and their behaviors were compared in response to trains of inputs activating NMDA, AMPA and GABA synapses. Injected current inputs were then used to investigate the mechanisms underlying the observed differences.
It was observed that the behavior of these two types of cells were different in several ways. For instance, Cell B when compared with Cell A (i) had a more depolarized mean down-state potential (+2.8 mV); (ii) had a mean burst strength (number of action potentials fired from an up-state) higher by 35% for same strength synaptic input (Figure 1A); (iii) showed noticeable differences in strength-duration curve; (iv) had a mean spike onset earlier by 14% for a given number of spikes fired from the up-state (Figure 1B). It was also found that while the higher input resistance offered by Cell B is responsible for the earlier spiking onset, the lower permeability to potassium ions underlies the enhanced burst strength.
Our model demonstrates the facilitatory effect of KIR current inactivation on MSN excitability in response to synaptic inputs. In view of the reports that dendritic intracellular calcium levels depend closely on burst strength as well as the spike onset time in MSNs , our findings suggest that KIR current inactivation may significantly modulate synaptic plasticity as well.
Mermelstein PG, Song W, Tkatch T, Yan Z, Surmeier DJ: Inwardly rectifying potassium (IRK) currents are correlated with IRK subunit expression in rat nucleus accumbens medium spiny neurons. J Neurosci. 1998, 18: 6650-6661.
Kerr JND, Plenz D: Action potential timing determines dendritic calcium during striatal up-states. J Neurosci. 2004, 24: 877-8852. 10.1523/JNEUROSCI.4475-03.2004.
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Steephen, J.E., Manchanda, R. Modulation of synaptically induced burst strength and spike onset timing by inactivating KIRcurrents in medium spiny neurons. BMC Neurosci 9, P57 (2008). https://doi.org/10.1186/1471-2202-9-S1-P57
- Synaptic Plasticity
- Lower Permeability
- Onset Time
- Facilitatory Effect
- Synaptic Input