title: Reduction in cortical parvalbumin expression due to intermittent theta-burst stimulation correlates with maturation of the perineuronal nets in young rats.
abstract: We recently showed that intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast-spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age-dependent. Conscious Sprague-Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS-related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8-9%) did not change with age in sham-controls and also the increase in cortical c-Fos expression induced by iTBS was not principally age-dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35 d to enable activity-dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity.
authors: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, Bochum, 44780, Germany.
authors: Annika
authors: A
authors: Mix
authors: Kathrin
authors: K
authors: Hoppenrath
authors: Klaus
authors: K
authors: Funke
mesh_terms: D000367:Age Factors; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation
chemical_list: D010320:Parvalbumins
keywords: cortical critical period; cortical interneurons; inhibitory systems; repetitive transcranial magnetic stimulation; theta-burst stimulation; transcranial magnetic stimulation