Hyperconnectivity, slow synapses in PFC mental retardation and autism model (Testa-Silva et al 2011)

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Accession:140033
The subdirectory 'matlab' contains MATLAB scripts (The Mathworks, USA) that can be used to reproduce the panels of Figures 4-5. This directory contains files to reproduce sample computer simulations presented in the 2011 paper authored by Meredith, R., Testa-Silva, G., Loebel, A., Giugliano, M., de Kock, C.; Mansvelder, H. "Hyperconnectivity and slow synapses in prefrontal cortex of a model for mental retardation and autism". ABSTRACT "... We propose that these findings are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low frequency stimulation, which may explain deficits in integration and information processing in attentional neuronal networks in neurodevelopmental disorders."
Reference:
1 . Testa-Silva G, Loebel A, Giugliano M, de Kock CP, Mansvelder HD, Meredith RM (2011) Hyperconnectivity and Slow Synapses during Early Development of Medial Prefrontal Cortex in a Mouse Model for Mental Retardation and Autism Cerebral Cortex 22(6):1333-42 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Synapse; Neural mass;
Brain Region(s)/Organism: Neocortex; Prefrontal cortex (PFC);
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: MATLAB;
Model Concept(s): Activity Patterns; Oscillations; Short-term Synaptic Plasticity; Attractor Neural Network;
Implementer(s): Giugliano, Michele [mgiugliano at gmail.com]; Loebel, Alex [alex.loebel at gmail.com];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell;
  
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ModelDB_June2011
matlab
README.txt
                            
This directory contains files to reproduce sample computer simulations
presented in the 2011 paper authored by

Meredith, R., Testa-Silva, G., Loebel, A., Giugliano, M., de Kock, C.;
Mansvelder, H.  "Hyperconnectivity and slow synapses in prefrontal
cortex of a model for mental retardation and autism".


ABSTRACT

Neuronal theories of neurodevelopmental disorders of autism and mental
retardation propose that abnormal connectivity underlies deficits in
attentional processing. We tested this by studying unitary synaptic
connections between layer 5 pyramidal neurons within medial prefrontal
cortex networks in the Fmr1-KO mouse model for mental retardation and
autism. In line with predictions from neurocognitive theory, we found
that neighbouring pyramidal neurons were hyperconnected. Surprisingly,
these excitatory synaptic connections between Fmr1-KO pyramidal
neurons showed a 30% delayed onset of postsynaptic responses to single
presynaptic action potentials. Furthermore, the synapses failed to
recover from short-term synaptic depression as quickly as WT synaptic
connections.

We propose that these findings are tightly linked: using a network
model, we show that slower synapses are essential to counterbalance
hyperconnectivity in order to maintain a dynamic range of excitatory
activity. However, the slow synaptic time constants induce decreased
responsiveness to low frequency stimulation, which may explain
deficits in integration and information processing in attentional
neuronal networks in neurodevelopmental disorders.


Model implementers: M. Giugliano and A. Loebel

The subdirectory 'matlab' contains MATLAB scripts (The Mathworks, USA)
that can be used to reproduce the panels of Figures 4-5.

For any question on the model implementation, feel free to contact:
alex.loebel@gmail.com and michele.giugliano@ua.ac.be

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