Induction and modulation of persistent activity in a layer V PFC microcircuit model
Working memory refers to the temporary storage of information and is strongly associated with the prefrontal cortex (PFC). Persistent activity of cortical neurons, namely the activity that persists beyond the stimulus presentation, is considered the cellular correlate of working memory. Although pas...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-10-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncir.2013.00161/full |
| _version_ | 1818214589684252672 |
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| author | Athanasia ePapoutsi Athanasia ePapoutsi Kyriaki eSidiropoulou Kyriaki eSidiropoulou Vassilis eCutsuridis Panayiota ePoirazi |
| author_facet | Athanasia ePapoutsi Athanasia ePapoutsi Kyriaki eSidiropoulou Kyriaki eSidiropoulou Vassilis eCutsuridis Panayiota ePoirazi |
| author_sort | Athanasia ePapoutsi |
| collection | DOAJ |
| description | Working memory refers to the temporary storage of information and is strongly associated with the prefrontal cortex (PFC). Persistent activity of cortical neurons, namely the activity that persists beyond the stimulus presentation, is considered the cellular correlate of working memory. Although past studies suggested that this type of activity is characteristic of large scale networks, recent experimental evidence imply that small, tightly interconnected clusters of neurons in the cortex may support similar functionalities. However, very little is known about the biophysical mechanisms giving rise to persistent activity in small-sized microcircuits in the prefrontal cortex. Here, we present a detailed biophysically –yet morphologically simplified- microcircuit model of layer V PFC neurons that incorporates connectivity constraints and is validated against a multitude of experimental data. We show that (a) a small-sized network can exhibit persistent activity under realistic stimulus conditions. (b) Its emergence depends strongly on the interplay of dADP, NMDA and GABAB currents. (c) Although increases in stimulus duration increase the probability of persistent activity induction, variability in the stimulus firing frequency does not consistently influence it. (d) Modulation of ionic conductances (Ih, ID, IsAHP, IcaL, IcaN, IcaR) differentially controls persistent activity properties in a location dependent manner. These findings suggest that modulation of the microcircuit’s firing characteristics is achieved primarily through changes in its intrinsic mechanism makeup, supporting the hypothesis of multiple bi-stable units in the PFC. Overall, the model generates a number of experimentally testable predictions that may lead to a better understanding of the biophysical mechanisms of persistent activity induction and modulation in the prefrontal cortex. |
| first_indexed | 2024-12-12T06:22:35Z |
| format | Article |
| id | doaj.art-f2dd340836f644e996cf3dfe5c963313 |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-12-12T06:22:35Z |
| publishDate | 2013-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-f2dd340836f644e996cf3dfe5c9633132022-12-22T00:34:52ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102013-10-01710.3389/fncir.2013.0016156796Induction and modulation of persistent activity in a layer V PFC microcircuit modelAthanasia ePapoutsi0Athanasia ePapoutsi1Kyriaki eSidiropoulou2Kyriaki eSidiropoulou3Vassilis eCutsuridis4Panayiota ePoirazi5Foundation for Research and Technology - Hellas (FORTH)University of CreteFoundation for Research and Technology - Hellas (FORTH)University of CreteFoundation for Research and Technology - Hellas (FORTH)Foundation for Research and Technology - Hellas (FORTH)Working memory refers to the temporary storage of information and is strongly associated with the prefrontal cortex (PFC). Persistent activity of cortical neurons, namely the activity that persists beyond the stimulus presentation, is considered the cellular correlate of working memory. Although past studies suggested that this type of activity is characteristic of large scale networks, recent experimental evidence imply that small, tightly interconnected clusters of neurons in the cortex may support similar functionalities. However, very little is known about the biophysical mechanisms giving rise to persistent activity in small-sized microcircuits in the prefrontal cortex. Here, we present a detailed biophysically –yet morphologically simplified- microcircuit model of layer V PFC neurons that incorporates connectivity constraints and is validated against a multitude of experimental data. We show that (a) a small-sized network can exhibit persistent activity under realistic stimulus conditions. (b) Its emergence depends strongly on the interplay of dADP, NMDA and GABAB currents. (c) Although increases in stimulus duration increase the probability of persistent activity induction, variability in the stimulus firing frequency does not consistently influence it. (d) Modulation of ionic conductances (Ih, ID, IsAHP, IcaL, IcaN, IcaR) differentially controls persistent activity properties in a location dependent manner. These findings suggest that modulation of the microcircuit’s firing characteristics is achieved primarily through changes in its intrinsic mechanism makeup, supporting the hypothesis of multiple bi-stable units in the PFC. Overall, the model generates a number of experimentally testable predictions that may lead to a better understanding of the biophysical mechanisms of persistent activity induction and modulation in the prefrontal cortex.http://journal.frontiersin.org/Journal/10.3389/fncir.2013.00161/fullPrefrontal CortexNMDAGABABcomputer modelingintrinsic membrane propertiesdADP |
| spellingShingle | Athanasia ePapoutsi Athanasia ePapoutsi Kyriaki eSidiropoulou Kyriaki eSidiropoulou Vassilis eCutsuridis Panayiota ePoirazi Induction and modulation of persistent activity in a layer V PFC microcircuit model Frontiers in Neural Circuits Prefrontal Cortex NMDA GABAB computer modeling intrinsic membrane properties dADP |
| title | Induction and modulation of persistent activity in a layer V PFC microcircuit model |
| title_full | Induction and modulation of persistent activity in a layer V PFC microcircuit model |
| title_fullStr | Induction and modulation of persistent activity in a layer V PFC microcircuit model |
| title_full_unstemmed | Induction and modulation of persistent activity in a layer V PFC microcircuit model |
| title_short | Induction and modulation of persistent activity in a layer V PFC microcircuit model |
| title_sort | induction and modulation of persistent activity in a layer v pfc microcircuit model |
| topic | Prefrontal Cortex NMDA GABAB computer modeling intrinsic membrane properties dADP |
| url | http://journal.frontiersin.org/Journal/10.3389/fncir.2013.00161/full |
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