FOR 2143:  Interneuron Synaptic Plasticity - From Mechanisms to Functions

• Subject Area: Biology ; Medicine
• Term: since 2014
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656

A fundamental feature of the mammalian brain is its ability to acquire, store and recall novel information, which enables the individual organism to flexibly adapt to its changing environment. Memory formation dependents on the capacity of nerve cells to change the efficacy of their communication points, the synapses. These plastic changes depend on correlated neuronal activity of communicating neurons and are expressed as long-term potentiation (LTP) or the opposite long-term depression (LTD) of synaptic transmission. Almost 50 years ago synaptic plasticity was first identified at glutamatergic terminals in networks of excitatory principal cells (Hebb, 1949; Bliss & Lomo, 1973). Since then synaptic plasticity has been broadly accepted as the main cellular mechanism underlying learning and memory in the mammalian brain (Malenka, 2003; Feldman & Brecht, 2005). Recent investigations, including our own, demonstrated that plasticity also exists at glutamatergic synapses targeting GABAergic inhibitory interneurons (INs; Isaac et al., 2007; Kullmann & Lamsa, 2007; Lange et al., 2012; Topolnik, 2012). Moreover, an unexpected variety in the conditions and forms of IN plasticity has been identified (Kullmann & Lamsa, 2011), raising the possibility that IN plasticity could contribute to information processing in a very versatile, cell type- and synapse-specific manner. Therefore, in the proposed RU, we aim to decipher the contribution of IN plasticity to learning and memory in a dual approach. First, in a ‘bottom up’ approach, we aim to identify the main cellular and molecular mechanisms underlying synaptic plasticity in INs. Second, in a ‘bottom up’ approach we will develop and use new molecular tools to modulate some of the main molecular pathways underlying IN plasticity. In the 1st funding period of the research unit (RU) we successfully focused this approach on synaptic plasticity in parvalbumin-expressing persioma-inhibitory (PVI) and somatostatin-expressing dendrite-targeting interneurons (SOMIs). In the 2nd proposed funding period we aim to follow our initially set research lines and to particularly draw a causal link between IN plasticity, neuronal network activity and memory-relevant behaviour. To achieve this goal, we will combine in vivo and in vitro electrophysiology, neuroanatomy, in vivo imaging, molecular biology, optogenetics, behavioural and computational analyses in a concerted, integrative and causal manner.

• DFG Programme: Research Units
• International Connection: Austria

Projects

• Computational consequences of interneuron plasticity (Applicant Sprekeler, Henning )
• Coordination Funds (Applicant Bartos, Marlene )
• Die Rolle der Plastizität von Interneuronen bei der inhibitorischen Kontrolle von Zielbewegungen (Applicant Poulet, Ph.D., James F.A. )
• GABAB receptor-mediated regulation of synaptic plasticity in interneurons (Applicant Vida, Imre )
• Interneuron plasticity during spatial learning (Applicant Csicsvari, Jozsef )
• Mechanisms underlying dentate gyrus interneuron plasticity and their role in controlling population activity /in vivo/ (Applicant Bartos, Marlene )
• Subcellular distribution and dynamics of neurotransmitter receptors and Cav channels in interneuron plasticity (Applicant Kulik, Akos )
• The impact of interneuron plasticity on engram and memory formation in the hippocampus (Applicant Wulff, Peer )
• The role of interneuron plasticity in the generation of fast local network oscillations (Applicant Geiger, Jörg )
• The role of parvalbumin positive interneuron activity and plasticity in the prefrontal cortex for movement control (Applicant Diester, Ilka )

• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Spokesperson: Professorin Dr. Marlene Bartos