Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex.
The application of new experimental techniques in vivo has shed light on the wiring diagram of cortical networks, revealing the highly non-random connectivity of pyramidal neurons. This structured connectivity is characterized by distance-dependent formation of neuronal clusters and over-represented...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-03-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/conf.fnsys.2014.05.00030/full |
| _version_ | 1811307977295003648 |
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| author | Stefanos Stefanou - Stamatiadis Stefanos Stefanou - Stamatiadis |
| author_facet | Stefanos Stefanou - Stamatiadis Stefanos Stefanou - Stamatiadis |
| author_sort | Stefanos Stefanou - Stamatiadis |
| collection | DOAJ |
| description | The application of new experimental techniques in vivo has shed light on the wiring diagram of cortical networks, revealing the highly non-random connectivity of pyramidal neurons. This structured connectivity is characterized by distance-dependent formation of neuronal clusters and over-represented structural ‘motifs’ (Perin 2011, Ko 2013). In the prefrontal cortex (PFC) in particular, pyramidal neurons were shown to form hyper-clusters, compared to other sensory regions. Yet, very little is known about the functional properties of these microcircuits and their role in Persistent Activity (PA), a well known function of the PFC. PA is the spiking activity that persists beyond the stimulus presentation and is considered to be the cellular correlate of working memory. Although, PA was traditionally assumed to emerge in large scale networks, recent in vivo data in the PFC suggest that small microcircuits mediate its functional output (Durstwitz, 2010). <br/>Motivated by the above findings this work probes the role of realistic connectivity constraints in shaping the functional output of PFC, through simulations of biophysically and morphologically detailed PFC circuits. Towards this goal, we used a compartmental modeling approach, whereby layer 5 PFC pyramidal neurons are modeled with detailed morphological and biophysical properties. Three different types of interneurons were also implemented; the Fast-spiking (FS), Regular-spiking (RS), and Irregular-spiking (IS). These were biophysically detailed, yet morphologically simplified. Microcircuits consisted of 75 pyramidal neurons, 13 FS, 6 RS and 6 IS. Properties (location /number /amplitude /kinetics) of both excitatory and inhibitory synapses were extensively validated against experimental data. <br/>The network model was used to investigate the effect of connectivity on the emergence of persistent activity. Two different connectivity profiles of pyramidal cells were implemented: one highly non-random (structured) and one random. In the structured network, the connection probability was (a) distance-dependent, (b) local clustering dependent, based on experimental data, whereas at the random microcircuit, each pair was connected independently with fixed probability. Both types of microcircuits exhibited the same overall connection probability. Using the same stimulation protocol, directed in a sub-region of each network, we examined the ability of each microcircuit to hold and distribute persistent activity to neighboring neurons, as well as its spiking profile. Preliminarily results suggest that structurally connected microcircuits are characterized by different activity attributes, suggesting that the wiring diagram plays a key role in the formation of functionally distinct processing clusters in the PFC. <br/> <br/> <br/>References: <br/> <br/>Durstewitz, D., Vittoz, N. M., Floresco, S. B., & Seamans, J. K. (2010). Abrupt transitions between prefrontal neural ensemble states accompany behavioral transitions during rule learning. Neuron, 66(3), 438–48. doi:10.1016/j.neuron.2010.03.029 <br/> <br/>Ko, H., Cossell, L., Baragli, C., Antolik, J., Clopath, C., Hofer, S. B., & Mrsic-Flogel, T. D. (2013). The emergence of functional microcircuits in visual cortex. Nature, 496(7443), 96–100. doi:10.1038/nature12015 <br/> <br/>Perin, R., Berger, T. K., & Markram, H. (2011). A synaptic organizing principle for cortical neuronal groups. Proceedings of the National Academy of Sciences of the United States of America, 108(13), 5419–24. doi:10.1073/pnas.1016051108 <br/> |
| first_indexed | 2024-04-13T09:14:53Z |
| format | Article |
| id | doaj.art-e497a0ed852d4a8f9e7389fbe5b63177 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-04-13T09:14:53Z |
| publishDate | 2014-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-e497a0ed852d4a8f9e7389fbe5b631772022-12-22T02:52:46ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372014-03-01810.3389/conf.fnsys.2014.05.0003092474Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex.Stefanos Stefanou - Stamatiadis0Stefanos Stefanou - Stamatiadis1Foundation for Research and Technology, HellasDepartment of Biology, University of Crete, Heraklion, GreeceThe application of new experimental techniques in vivo has shed light on the wiring diagram of cortical networks, revealing the highly non-random connectivity of pyramidal neurons. This structured connectivity is characterized by distance-dependent formation of neuronal clusters and over-represented structural ‘motifs’ (Perin 2011, Ko 2013). In the prefrontal cortex (PFC) in particular, pyramidal neurons were shown to form hyper-clusters, compared to other sensory regions. Yet, very little is known about the functional properties of these microcircuits and their role in Persistent Activity (PA), a well known function of the PFC. PA is the spiking activity that persists beyond the stimulus presentation and is considered to be the cellular correlate of working memory. Although, PA was traditionally assumed to emerge in large scale networks, recent in vivo data in the PFC suggest that small microcircuits mediate its functional output (Durstwitz, 2010). <br/>Motivated by the above findings this work probes the role of realistic connectivity constraints in shaping the functional output of PFC, through simulations of biophysically and morphologically detailed PFC circuits. Towards this goal, we used a compartmental modeling approach, whereby layer 5 PFC pyramidal neurons are modeled with detailed morphological and biophysical properties. Three different types of interneurons were also implemented; the Fast-spiking (FS), Regular-spiking (RS), and Irregular-spiking (IS). These were biophysically detailed, yet morphologically simplified. Microcircuits consisted of 75 pyramidal neurons, 13 FS, 6 RS and 6 IS. Properties (location /number /amplitude /kinetics) of both excitatory and inhibitory synapses were extensively validated against experimental data. <br/>The network model was used to investigate the effect of connectivity on the emergence of persistent activity. Two different connectivity profiles of pyramidal cells were implemented: one highly non-random (structured) and one random. In the structured network, the connection probability was (a) distance-dependent, (b) local clustering dependent, based on experimental data, whereas at the random microcircuit, each pair was connected independently with fixed probability. Both types of microcircuits exhibited the same overall connection probability. Using the same stimulation protocol, directed in a sub-region of each network, we examined the ability of each microcircuit to hold and distribute persistent activity to neighboring neurons, as well as its spiking profile. Preliminarily results suggest that structurally connected microcircuits are characterized by different activity attributes, suggesting that the wiring diagram plays a key role in the formation of functionally distinct processing clusters in the PFC. <br/> <br/> <br/>References: <br/> <br/>Durstewitz, D., Vittoz, N. M., Floresco, S. B., & Seamans, J. K. (2010). Abrupt transitions between prefrontal neural ensemble states accompany behavioral transitions during rule learning. Neuron, 66(3), 438–48. doi:10.1016/j.neuron.2010.03.029 <br/> <br/>Ko, H., Cossell, L., Baragli, C., Antolik, J., Clopath, C., Hofer, S. B., & Mrsic-Flogel, T. D. (2013). The emergence of functional microcircuits in visual cortex. Nature, 496(7443), 96–100. doi:10.1038/nature12015 <br/> <br/>Perin, R., Berger, T. K., & Markram, H. (2011). A synaptic organizing principle for cortical neuronal groups. Proceedings of the National Academy of Sciences of the United States of America, 108(13), 5419–24. doi:10.1073/pnas.1016051108 <br/>http://journal.frontiersin.org/Journal/10.3389/conf.fnsys.2014.05.00030/fullconnectivityPersistent activitycompartmental modelingmicrocircuitsstructured connectivityneuronal clustersfunctional output |
| spellingShingle | Stefanos Stefanou - Stamatiadis Stefanos Stefanou - Stamatiadis Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. Frontiers in Systems Neuroscience connectivity Persistent activity compartmental modeling microcircuits structured connectivity neuronal clusters functional output |
| title | Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. |
| title_full | Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. |
| title_fullStr | Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. |
| title_full_unstemmed | Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. |
| title_short | Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex. |
| title_sort | structured connectivity shapes microcircuit function in the prefrontal cortex |
| topic | connectivity Persistent activity compartmental modeling microcircuits structured connectivity neuronal clusters functional output |
| url | http://journal.frontiersin.org/Journal/10.3389/conf.fnsys.2014.05.00030/full |
| work_keys_str_mv | AT stefanosstefanoustamatiadis structuredconnectivityshapesmicrocircuitfunctionintheprefrontalcortex AT stefanosstefanoustamatiadis structuredconnectivityshapesmicrocircuitfunctionintheprefrontalcortex |