Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).ORCID-id: 0000-0002-8044-9195
KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).ORCID-id: 0000-0002-0550-0739
2017 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 4, s. 1-17Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Network oscillations are ubiquitous across many brain regions. In the basal ganglia, oscillations are also present at many levels and a wide range of characteristic frequencies have been reported to occur during both health and disease. The striatum, the main input nucleus of the basal ganglia, receives massive glutamatergic inputs from the cortex and is highly susceptible to external oscillations. However, there is limited knowledge about the exact nature of this routing process and therefore, it is of key importance to understand how time-dependent, external stimuli propagate through the striatal circuitry. Using a network model of the striatum and corticostriatal projections, we try to elucidate the importance of specific GABAergic neurons and their interactions in shaping striatal oscillatory activity. Here, we propose that fast-spiking interneurons can perform an important role in transferring cortical oscillations to the striatum especially to those medium spiny neurons that are not directly driven by the cortical oscillations. We show how the activity levels of different populations, the strengths of different inhibitory synapses, degree of outgoing projections of striatal cells, ongoing activity and synchronicity of inputs can influence network activity. These results suggest that the propagation of oscillatory inputs into the medium spiny neuron population is most efficient, if conveyed via the fast-spiking interneurons. Therefore, pharmaceuticals that target fast-spiking interneurons may provide a novel treatment for regaining the spectral characteristics of striatal activity that correspond to the healthy state.

Ort, förlag, år, upplaga, sidor
2017. Vol. 12, nr 4, s. 1-17
Nyckelord [en]
striatum, fast-spiking interneurons, network oscillations, medium spiny neurons, GABAergic transmission, corticostriatal interactions
Nationell ämneskategori
Datavetenskap (datalogi) Biologiska vetenskaper
Forskningsämne
Datalogi
Identifikatorer
URN: urn:nbn:se:kth:diva-205220DOI: 10.1371/journal.pone.0175135ISI: 000399371900097Scopus ID: 2-s2.0-85017146743OAI: oai:DiVA.org:kth-205220DiVA, id: diva2:1087783
Anmärkning

QC 20170411

Tillgänglig från: 2017-04-10 Skapad: 2017-04-10 Senast uppdaterad: 2018-02-09Bibliografiskt granskad
Ingår i avhandling
1. Untangling Cortico-Striatal Circuitry and its Role in Health and Disease - A computational investigation
Öppna denna publikation i ny flik eller fönster >>Untangling Cortico-Striatal Circuitry and its Role in Health and Disease - A computational investigation
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The basal ganglia (BG) play a critical role in a variety of regular motor and cognitive functions. Many brain diseases, such as Parkinson’s diseases, Huntington’s disease and dyskinesia, are directly related to malfunctions of the BG nuclei. One of those nuclei, the input nucleus called the striatum, is heavily connected to the cortex and receives afferents from nearly all cortical areas. The striatum is a recurrent inhibitory network that contains several distinct cell types. About 95% of neurons in the striatum are medium spiny neurons (MSNs) that form the only output from the striatum. Two of the most examined sources of GABAergic inhibition into MSNs are the feedback inhibition (FB) from the axon collaterals of the MSNs themselves, and the feedforward inhibition (FF) via the small population (1-2% of striatal neurons) of fast spiking interneurons (FSIs). The cortex sends direct projections to the striatum, while the striatum can affect the cortex only indirectly through other BG nuclei and the thalamus. Understanding how different components of the striatal network interact with each other and influence the striatal response to cortical inputs has crucial importance for clarifying the overall functions and dysfunctions of the BG.

    In this thesis I have employed advanced experimental data analysis techniques as well as computational modelling, to study the complex nature of cortico-striatal interactions. I found that for pathological states, such as Parkinson’s disease and L-DOPA-induced dyskinesia, effective connectivity is bidirectional with an accent on the striatal influence on the cortex. Interestingly, in the case of L-DOPA-induced dyskinesia, there was a high increase in effective connectivity at ~80 Hz and the results also showed a large relative decrease in the modulation of the local field potential amplitude (recorded in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats) at ~80 Hz by the phase of low frequency oscillations. These results suggest a lack of coupling between the low frequency activity of a presumably larger neuronal population and the synchronized activity of a presumably smaller group of neurons active at 80 Hz.

    Next, I used a spiking neuron network model of the striatum to isolate the mechanisms underlying the transmission of cortical oscillations to the MSN population. I showed that FSIs play a crucial role in efficient propagation of cortical oscillations to the MSNs that did not receive direct cortical oscillations. Further, I have identified multiple factors such as the number of activated neurons, ongoing activity, connectivity, and synchronicity of inputs that influenced the transfer of oscillations by modifying the levels of FB and FF inhibitions. Overall, these findings reveal a new role of FSIs in modulating the transfer of information from the cortex to striatum. By modulating the activity and properties of the FSIs, striatal oscillations can be controlled very efficiently. Finally, I explored the interactions in the striatal network with different oscillation frequencies and showed that the features of those oscillations, such as amplitude and frequency fluctuations, can be influenced by a change in the input intensities into MSNs and FSIs and that these fluctuations are also highly dependent on the selected frequencies in addition to the phase offset between different cortical inputs.

    Lastly, I investigated how the striatum responds to cortical neuronal avalanches. Recordings in the striatum revealed that striatal activity was also characterized by spatiotemporal clusters that followed a power law distribution albeit, with significantly steeper slope. In this study, an abstract computational model was developed to elucidate the influence of intrastriatal inhibition and cortico-striatal interplay as important factors to understand the experimental findings. I showed that one particularly high activation threshold of striatal nodes can reproduce a power law-like distribution with a coefficient similar to the one found experimentally. By changing the ratio of excitation and inhibition in the cortical model, I saw that increased activity in the cortex strongly influenced striatal dynamics, which was reflected in a less negative slope of cluster size distributions in the striatum.  Finally, when inhibition was added to the model, cluster size distributions had a prominently earlier deviation from the power law distribution compared to the case when inhibition was not present. 

Ort, förlag, år, upplaga, sidor
Stockholm: KTH Royal Institute of Technology, 2018. s. 88
Serie
TRITA-EECS-AVL ; 2018:9
Nyckelord
cortico-striatal circuits, levodopa-induced dyskinesia, Parkinson’s disease, effective connectivity, cross-frequency coupling, corticostriatal network, network oscillations, GABAergic transmission. basal ganglia, striatum, cortex, fast spiking interneurons, medium spiny neurons, neuronal avalanches
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
urn:nbn:se:kth:diva-222467 (URN)978-91-7729-676-8 (ISBN)
Disputation
2018-03-05, F3, Lindstedtsvägen 26, KTH Campus, Stockholm, 13:15 (Engelska)
Opponent
Handledare
Anmärkning

QC 20180209

Tillgänglig från: 2018-02-09 Skapad: 2018-02-09 Senast uppdaterad: 2018-06-12Bibliografiskt granskad

Open Access i DiVA

fulltext(4353 kB)105 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 4353 kBChecksumma SHA-512
81ddf99cddfe3da3fe087ffc38a205b17ef78b1253f02ab1d563e4f11188d906703220f9118ce9a7508dedcfc80b429a31366fef858f5c31a11160d17194ce59
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextScopusPublishers web site

Sök vidare i DiVA

Av författaren/redaktören
Belić, JovanaKumar, ArvindHellgren Kotaleski, Jeanette
Av organisationen
Beräkningsvetenskap och beräkningsteknik (CST)
I samma tidskrift
PLoS ONE
Datavetenskap (datalogi)Biologiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 105 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 1920 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf