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GABAergic microcircuits govern the corticostriatal spike-timing dependent plasticity
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.ORCID iD: 0000-0002-0550-0739
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2010 (English)Conference paper (Refereed)
Abstract [en]

We investigated the corticostriatal spike timing-dependentplasticity (STDP) at medium-sized spiny neurons (MSNs) as aHebbian learning rule. Here, we show that GABAergic microcircuitsgovern the spike-timing dependence. Indeed, whenGABAergic transmission was blocked (by GABAA blockers)the spike-timing dependence was totally reversed when comparedto control conditions. Post-pre pairings induced t-LTDand pre-post pairings induced t-LTP. In both control andGABAA blockade conditions, the t-LTP was NMDA receptordependent and the t-LTD was endocannabinoid dependent.The GABAergic inhibition at MSNs arises mainly from fastspiking interneurons. Indeed, we observed, in paravalbumin-GFP mice, that during STDP pairings fast-spiking interneuronsdischarge and exert a strong synaptic inhibitory weight onMSNs. In addition, both tonic and phasic components of suchGABAergic inhibition were involved in the spike-timing dependence.We observed a developmental shift of the spiketimingdependence correlated with the maturation of theGABAergic microcircuits: at P8-10, post-pre pairings induced t-LTD and pre-post pairings induced t-LTP, while a reversedSTDP timing-dependence was found after P20. To further ourunderstanding on dendritic GABAergic signal integration inMSNs, we simulated the experimental STDP protocols using abiophysically detailed MSN model. The simulation results predicteda significant influence of GABAergic inputs in distaldendrites, although not visible in the soma. Moreover, oursimulations showed that the balance between NMDA calciumand L-type calcium voltage channels could be shifted by eithertonic or phasic GABAergic inputs, or by their combinations.This in turn could influence whether NMDA-dependent LTP orL-type calcium- (also endocannabinoid-) dependent LTD occurs.In conclusion, we demonstrated that GABAergic microcircuitstightly govern the corticostriatal plasticity and re-orientate STDP along development.

Place, publisher, year, edition, pages
2010. P-70- p.
National Category
Computer and Information Science
URN: urn:nbn:se:kth:diva-58757OAI: diva2:473946
IBAGS X, Tenth Triennial Meeting, Ocean Place Resort, Long Branch NJ, June 20-24, 2010
QC 20120109Available from: 2012-01-08 Created: 2012-01-08 Last updated: 2012-01-09Bibliographically approved

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