Linking the molecular organization of active zones to temporal neural coding
Final Report Abstract
Information processing in the brain relies on the exact encoding of sensory stimuli to generate a consistent and reliable output. In the nervous system, neuronal activity is relayed, filtered, and integrated via chemical synapses. Therefore, temporal codes, i.e. where precise spike timing carries coding information, are expected to depend critically on the properties of neurotransmitter release from the presynaptic active zone (AZ). However, the causal relation between AZ physiology and temporal codes has not yet been studied in detail. The molecular architecture of the AZ affects the timing and stability of synaptic exocytosis. AZ proteins, such as Drosophila Bruchpilot (Brp), influence the temporal precision of excitation-secretion coupling and modulate sustained transmitter release during continuous synaptic activity. The present project aimed to investigate how the molecular organization of the AZ affects the neural temporal code - its precision and its stability at different stimulation intensities. Focusing on synapses between sensory neurons and second order neurons in the olfactory system of Drosophila melanogaster, we obtained a deeper mechanistic understanding of how synaptic function shapes neural coding in the live, behaving animal. The results show that the properties of the AZ are critical for generating a reliable neural code. Reducing neurotransmitter release probability of olfactory sensory neurons disrupts both neural coding and behavioral reliability. Strikingly, a target-specific homeostatic increase of Brp-positive AZ numbers rescues these defects within a day. These findings demonstrate an important role for synaptic plasticity in maintaining neural coding reliability and are of pathophysiological interest by uncovering an elegant mechanism through which the neural circuitry can counterbalance perturbations.
Publications
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Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination. eLife, 9.
Dannhäuser, Sven; Lux, Thomas J.; Hu, Chun; Selcho, Mareike; Chen, Jeremy T.-C.; Ehmann, Nadine; Sachidanandan, Divya; Stopp, Sarah; Pauls, Dennis; Pawlak, Matthias; Langenhan, Tobias; Soba, Peter; Rittner, Heike L. & Kittel, Robert J.
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Controlling the behaviour of Drosophila melanogaster via smartphone optogenetics. Scientific Reports, 10(1).
Meloni, Ilenia; Sachidanandan, Divya; Thum, Andreas S.; Kittel, Robert J. & Murawski, Caroline
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Differential Role for a Defined Lateral Horn Neuron Subset in Naïve Odor Valence in Drosophila. Scientific Reports, 10(1).
Lerner, Hadas; Rozenfeld, Eyal; Rozenman, Bar; Huetteroth, Wolf & Parnas, Moshe
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Active zone compaction correlates with presynaptic homeostatic potentiation. Cell Reports, 37(1), 109770.
Mrestani, Achmed; Pauli, Martin; Kollmannsberger, Philip; Repp, Felix; Kittel, Robert J.; Eilers, Jens; Doose, Sören; Sauer, Markus; Sirén, Anna-Leena; Heckmann, Manfred & Paul, Mila M.
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Glial ER and GAP junction mediated Ca2+ waves are crucial to maintain normal brain excitability. Glia, 70(1), 123-144.
Weiss, Shirley; Clamon, Lauren C.; Manoim, Julia E.; Ormerod, Kiel G.; Parnas, Moshe & Littleton, J. Troy
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GPCR voltage dependence controls neuronal plasticity and behavior. Nature Communications, 12(1).
Rozenfeld, Eyal; Tauber, Merav; Ben-Chaim, Yair & Parnas, Moshe
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PACmn for improved optogenetic control of intracellular cAMP. BMC Biology, 19(1).
Yang, Shang; Constantin, Oana M.; Sachidanandan, Divya; Hofmann, Hannes; Kunz, Tobias C.; Kozjak-Pavlovic, Vera; Oertner, Thomas G.; Nagel, Georg; Kittel, Robert J.; Gee, Christine E. & Gao, Shiqiang
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The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release. Brain, 145(11), 3787-3802.
Paul, Mila M.; Dannhäuser, Sven; Morris, Lydia; Mrestani, Achmed; Hübsch, Martha; Gehring, Jennifer; Hatzopoulos, Georgios N.; Pauli, Martin; Auger, Genevieve M.; Bornschein, Grit; Scholz, Nicole; Ljaschenko, Dmitrij; Müller, Martin; Sauer, Markus; Schmidt, Hartmut; Kittel, Robert J.; DiAntonio, Aaron; Vakonakis, Ioannis; Heckmann, Manfred & Langenhan, Tobias
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Homeostatic synaptic plasticity rescues neural coding reliability. Nature Communications, 14(1).
Rozenfeld, Eyal; Ehmann, Nadine; Manoim, Julia E.; Kittel, Robert J. & Parnas, Moshe
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Rab3 mediates cyclic AMP-dependent presynaptic plasticity and olfactory learning.
Sachidanandan, Divya; Aravamudhan, Aishwarya; Mrestani, Achmed; Nerlich, Jana; Lamberty, Marius; Hasenauer, Natalie; Ehmann, Nadine; Pauls, Dennis; Seubert, Teresa; Maiellaro, Isabella; Selcho, Mareike; Heckmann, Manfred; Hallermann, Stefan & Kittel, Robert J.
