PMID- 24550786
OWN - NLM
STAT- MEDLINE
DCOM- 20140924
LR  - 20220129
IS  - 1662-5110 (Electronic)
IS  - 1662-5110 (Linking)
VI  - 8
DP  - 2014
TI  - Modulatory effects of inhibition on persistent activity in a cortical 
      microcircuit model.
PG  - 7
LID - 10.3389/fncir.2014.00007 [doi]
LID - 7
AB  - Neocortical network activity is generated through a dynamic balance between 
      excitation, provided by pyramidal neurons, and inhibition, provided by 
      interneurons. Imbalance of the excitation/inhibition ratio has been identified in 
      several neuropsychiatric diseases, such as schizophrenia, autism and epilepsy, 
      which also present with other cognitive deficits and symptoms associated with 
      prefrontal cortical (PFC) dysfunction. We undertook a computational approach to 
      study how changes in the excitation/inhibition balance in a PFC microcircuit 
      model affect the properties of persistent activity, considered the cellular 
      correlate of working memory function in PFC. To this end, we constructed a PFC 
      microcircuit, consisting of pyramidal neuron models and all three different 
      interneuron types: fast-spiking (FS), regular-spiking (RS), and irregular-spiking 
      (IS) interneurons. Persistent activity was induced in the microcircuit model with 
      a stimulus to the proximal apical dendrites of the pyramidal neuron models, and 
      its properties were analyzed, such as the induction profile, the interspike 
      intervals (ISIs) and neuronal synchronicity. Our simulations showed that (a) the 
      induction but not the firing frequency or neuronal synchronicity is modulated by 
      changes in the NMDA-to-AMPA ratio on FS interneuron model, (b) removing or 
      decreasing the FS model input to the pyramidal neuron models greatly limited the 
      biophysical modulation of persistent activity induction, decreased the ISIs and 
      neuronal synchronicity during persistent activity, (c) the induction and firing 
      properties could not be altered by the addition of other inhibitory inputs to the 
      soma (from RS or IS models), and (d) the synchronicity change could be reversed 
      by the addition of other inhibitory inputs to the soma, but beyond the levels of 
      the control network. Thus, generic somatic inhibition acts as a pacemaker of 
      persistent activity and FS specific inhibition modulates the output of the 
      pacemaker.
FAU - Konstantoudaki, Xanthippi
AU  - Konstantoudaki X
AD  - Department of Biology, University of Crete Heraklion, Greece ; Institute of 
      Molecular Biology and Biotechnology, Foundation for Research and Technology - 
      Hellas Heraklion, Greece.
FAU - Papoutsi, Athanasia
AU  - Papoutsi A
AD  - Department of Biology, University of Crete Heraklion, Greece ; Institute of 
      Molecular Biology and Biotechnology, Foundation for Research and Technology - 
      Hellas Heraklion, Greece.
FAU - Chalkiadaki, Kleanthi
AU  - Chalkiadaki K
AD  - Department of Biology, University of Crete Heraklion, Greece ; Institute of 
      Molecular Biology and Biotechnology, Foundation for Research and Technology - 
      Hellas Heraklion, Greece.
FAU - Poirazi, Panayiota
AU  - Poirazi P
AD  - Institute of Molecular Biology and Biotechnology, Foundation for Research and 
      Technology - Hellas Heraklion, Greece.
FAU - Sidiropoulou, Kyriaki
AU  - Sidiropoulou K
AD  - Department of Biology, University of Crete Heraklion, Greece ; Institute of 
      Molecular Biology and Biotechnology, Foundation for Research and Technology - 
      Hellas Heraklion, Greece.
LA  - eng
GR  - 311435/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140131
PL  - Switzerland
TA  - Front Neural Circuits
JT  - Frontiers in neural circuits
JID - 101477940
RN  - 0 (Parvalbumins)
SB  - IM
MH  - Action Potentials/*physiology
MH  - Cerebral Cortex/*physiology
MH  - Humans
MH  - Interneurons/physiology
MH  - *Models, Neurological
MH  - Nerve Net/*physiology
MH  - Neural Inhibition/*physiology
MH  - Parvalbumins/metabolism
MH  - Pyramidal Cells/physiology
MH  - Synapses/physiology
PMC - PMC3907788
OTO - NOTNLM
OT  - NMDA
OT  - connectivity
OT  - fast-spiking interneurons
OT  - parvalbumin interneurons
OT  - prefrontal cortex
OT  - synchronicity
EDAT- 2014/02/20 06:00
MHDA- 2014/09/25 06:00
PMCR- 2014/01/01
CRDT- 2014/02/20 06:00
PHST- 2013/11/01 00:00 [received]
PHST- 2014/01/14 00:00 [accepted]
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2014/09/25 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fncir.2014.00007 [doi]
PST - epublish
SO  - Front Neural Circuits. 2014 Jan 31;8:7. doi: 10.3389/fncir.2014.00007. 
      eCollection 2014.