title: How feedback inhibition shapes spike-timing-dependent plasticity and its implications for recent Schizophrenia models.
abstract: It has been shown that plasticity is not a fixed property but, in fact, changes depending on the location of the synapse on the neuron and/or changes of biophysical parameters. Here, we investigate how plasticity is shaped by feedback inhibition in a cortical microcircuit. We use a differential Hebbian learning rule to model spike-timing-dependent plasticity and show analytically that the feedback inhibition shortens the time window for LTD during spike-timing-dependent plasticity but not for LTP. We then use a realistic GENESIS model to test two hypothesis about interneuron hypofunction and conclude that a reduction in GAD67 is the most likely candidate as the cause for hypofrontality as observed in Schizophrenia.
authors.affiliation: School of Engineering, University of Glasgow, G12 8QQ, United Kingdom. bernd.porr@gla.ac.uk
authors.forename: Bernd
authors.initials: B
authors.lastname: Porr
authors.forename: Lynsey
authors.initials: L
authors.lastname: McCabe
authors.forename: Paolo
authors.initials: P
authors.lastname: di Prodi
authors.forename: Christoph
authors.initials: C
authors.lastname: Kolodziejski
authors.forename: Florentin
authors.initials: F
authors.lastname: Wörgötter
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology; D025461:Feedback, Physiological / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000378:metabolism; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1