Dynamik von axonaler Aktivität und neuronaler Plastizität bei schnellen Netzwerkoszillationen
Zusammenfassung der Projektergebnisse
Learning and memory are associated with modifications of the synapses that allow neurons within a particular neuronal network to communicate in a precisely timed manner. One crucial question in this interplay of neural and network activity is whether the resulting synchronized, rhythmic patterns of network activity, the network oscillations, are already capable of inducing synaptic plasticity. In this application, we examined the possibility that the CA3 network undergo activitydependent modification during the course of fast network oscillations and whether and how these modifications may influence the function of the network and lead to activity-dependent synaptic plasticity. Instead of electrical stimulation, as are commonly used in experimental studies of synaptic plasticity, we used pharmacologically induced gamma oscillations as a means. We show that gamma oscillations represent a basic mechanism to induce cell-specific plastic changes within a neuronal network and that these changes, reflecting neuronal network activity, are based on a mechanism whose key component is the excitatory metabotropic glutamate receptor 5. Pharmacological blocking of this receptor does not impair network oscillation, but prevent changes in network activity and synaptic plasticity. A further detailed analysis revealed that, in parallel to this facilitating network effect, the excitability of CA3 PCs was enhanced. In contrast to this excitatory neurons, the excitability of two types of perisomatic targeting inhibitory interneurons, PV-expressing and CCK-expressing cells, featured opposing effects: PV-expressing cells, promoting the emergence of gamma oscillations, exhibited enhanced activation, while CCK-expressing cells, whose activity interferes with gamma oscillations, showed a reduced excitability. The highly specific, contradirectional processes involved in regulating interneurons in turn might underline enhanced network excitability and thus promote synaptic plasticity. Dysregulation of the metabotropic glutamate receptor 5 has already been identified in several profound neurological disorders, such as schizophrenia, autistic spectrum disorders, and Down syndrome. Data from the current study demonstrate that these receptors play a central role in network oscillation-induced synaptic plasticity and highlight them in the general context of memory processing. If our hypothesis is proved right, results of the research may be beneficial for development of specific molecular tools to target normal and disturbed memory formation. Such tools could be also instrumental in mending cognitive decline induced by aging or neurodegenerative diseases. https://www.charite.de/en/service/press_reports/artikel/detail/berliner_forscher_ermitteln_ein_schluesselprotein_fuer_lernen_und_gedaechtnis
Projektbezogene Publikationen (Auswahl)
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(2013) GABA(B) autoreceptor-mediated cell type-specific reduction of inhibition in epileptic mice. Proc Natl Acad Sci USA 110:15073-15078
Dugladze T, Maziashvili N, Börgers C, Gurgenidze S, Häussler U, Winkelmann A, Haas CA, Meier JC, Vida I, Kopell NJ, Gloveli T
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(2014) Changes in neural network homeostasis trigger neuropsychiatric symptoms. J Clin Invest 124:696-711
Winkelmann A, Maggio N, Eller J, Caliskan G, Semtner M, Häussler U, Jüttner R, Dugladze T, Smolinsky B, Kowalczyk S, Chronowska E, Schwarz G, Rathjen FG, Rechavi G, Haas CA, Kulik A, Gloveli T, Heinemann U, Meier JC
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(2015) Cell type-specific separation of subicular principal neurons during network activities. PLoS One 10:e0123636
Eller J, Zarnadze S, Bäuerle P, Dugladze T, Gloveli T
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(2016) Cell-specific synaptic plasticity induced by network oscillations. Elife 24;5. pii: e14912
Zarnadze S, Bäuerle P, Santos-Torres J, Böhm C, Schmitz D, Geiger JR, Dugladze T, Gloveli T
