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The influence of stuttering properties for firing activity in pairs of electrically coupled striatal fast-spiking interneurons
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.ORCID iD: 0000-0002-0550-0739
2009 (English)In: Neuroinformatics 2009. Pilsen, Czech Republic, September 06 - 08,  2009, 2009Conference paper, Published paper (Other academic)
Abstract [en]

The striatum is the main input stage of the basal ganglia system, which is involved in executive functions of the forebrain – such as the planning and the selection of motor behavior. Feedforward inhibition of medium-sized spiny projection neurons in the striatum by fast-spiking interneurons is supposed to be an important determinant of controlling striatal output to later stages of the basal ganglia [1]. Striatal fast-spiking interneurons, which constitute approximately 1-2 % of all striatal neurons, show many similarities to cortical fast-spiking cells. In response to somatic current injection, for example, some of these neurons exhibit spike bursts with a variable number of action potentials (so called stuttering) [2-4]. Interestingly, the membrane potential between such stuttering episodes oscillates in the range of 20-100 Hz [3,5]. The first spike of each stuttering episode invariably occurs at a peak of the underlying subthreshold oscillation. In both cortex and striatum, fast-spiking cells have been shown to be inter-connected by gap junctions [6,7]. In vitro measurements as well as theoretical studies indicate that electrical coupling via gap junctions might be able to promote synchronous activity among these neurons [6,8].Here we use computational modeling to investigate how the presence of subthreshold oscillations and stuttering properties influence the synchronization of activity in pairs of electrically coupled fast-spiking neurons. We use the model of Golomb et al. [3], which we have extended with a dendritic tree in order to be able to simulate distal synaptic input. We show that gap junctions are able to synchronize both subthreshold membrane potential fluctuations as well as the stuttering periods in response to somatic current injection. In response to synaptic input, however, our model neuron rarely shows subthreshold oscillations, and the stuttering behavior changes to a firing pattern with single spikes or spike doublets. We furthermore investigate the effect of GABAergic (i.e. inhibitory) input to the model of the fast-spiking neuron and predict that inhibitory input is able to induce overlapping stuttering episodes in these cells. We finally discuss our results in the context of the feedforward inhibitory network which is likely to play an important role in striatal and basal ganglia function.

Place, publisher, year, edition, pages
2009.
National Category
Computer Science
Identifiers
URN: urn:nbn:se:kth:diva-14151DOI: 10.3389/conf.neuro.11.2009.08.102OAI: oai:DiVA.org:kth-14151DiVA: diva2:330830
Conference
Neuroinformatics 2009. Pilsen, Czech Republic, September 06 - 08, 2009
Note
QC 20100720Available from: 2010-07-20 Created: 2010-07-20 Last updated: 2012-01-08Bibliographically approved
In thesis
1. Computer Modelling of Neuronal Interactions in the Striatum
Open this publication in new window or tab >>Computer Modelling of Neuronal Interactions in the Striatum
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Large parts of the cortex and the thalamus project into the striatum,which serves as the input stage of the basal ganglia. Information isintegrated in the striatal neural network and then passed on, via themedium spiny (MS) projection neurons, to the output stages of thebasal ganglia. In addition to the MS neurons there are also severaltypes of interneurons in the striatum, such as the fast spiking (FS)interneurons. I focused my research on the FS neurons, which formstrong inhibitory synapses onto the MS neurons. These striatal FSneurons are sparsely connected by electrical synapses (gap junctions),which are commonly presumed to synchronise their activity.Computational modelling with the GENESIS simulator was used toinvestigate the effect of gap junctions on a network of synapticallydriven striatal FS neurons. The simulations predicted a reduction infiring frequency dependent on the correlation between synaptic inputsto the neighbouring neurons, but only a slight synchronisation. Thegap junction effects on modelled FS neurons showing sub-thresholdoscillations and stuttering behaviour confirm these results andfurther indicate that hyperpolarising inputs might regulate the onsetof stuttering.The interactions between MS and FS neurons were investigated byincluding a computer model of the MS neuron. The hypothesis was thatdistal GABAergic input would lower the amplitude of back propagatingaction potentials, thereby reducing the calcium influx in thedendrites. The model verified this and further predicted that proximalGABAergic input controls spike timing, but not the amplitude ofdendritic calcium influx after initiation.Connecting models of neurons written in different simulators intonetworks raised technical problems which were resolved by integratingthe simulators within the MUSIC framework. This thesis discusses theissues encountered by using this implementation and gives instructionsfor modifying MOOSE scripts to use MUSIC and provides guidelines forachieving compatibility between MUSIC and other simulators.This work sheds light on the interactions between striatal FS and MSneurons. The quantitative results presented could be used to developa large scale striatal network model in the future, which would beapplicable to both the healthy and pathological striatum.

Place, publisher, year, edition, pages
Stockholm: KTH, 2009. 79 p.
Series
Trita-CSC-A, ISSN 1653-5723 ; 2009:08
Keyword
striatum, fast spiking interneurons, medium spiny projection neurons, gap junctions, interoperability, MUSIC
National Category
Computer Science
Identifiers
urn:nbn:se:kth:diva-10523 (URN)978-91-7415-331-6 (ISBN)
Public defence
2009-06-11, Svedbergssalen (FD5), Roslagstullsbacken 21, Alba Nova, 09:00 (English)
Opponent
Supervisors
Note
QC 20100720Available from: 2009-06-03 Created: 2009-05-20 Last updated: 2010-07-20Bibliographically approved

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