SFB 1134:  Functional ensembles: cellular components, patterned activity and plasticity of co-active neurons in local networks

• Subject Area: Medicine
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243553651

• Final Report Year: 2020

Final Report Abstract

Perceptions, memories, thoughts, choices, actions and feelings have a physical correlate in the nervous system. Converging evidence indicates that such representations are given by the combined activity of multiple neurons. These groups of neurons, called ensembles, were the central theme of our Collaborative Research Centre. In order to understand neuronal representations we need an interdisciplinary approach towards the structure, spatio-temporal organization, cellular mechanisms, diversity, plasticity and functional role of neuronal ensembles. These studies can build on a wealth of knowledge about molecular-cellular and brain-wide systemic mechanisms, whereas concepts and tools for analysis of multi-cellular activity patterns are still emerging and constitute an own, highly dynamic field. Studying spatio-temporal activity patterns in neuronal networks would fill a major gap in understanding neuronal functions at different system levels. Indeed, it may be at the heart of the unsolved problem of the ‘neuronal code’. Our approach cut through different functional systems, brain regions, methods and models. What kept us together was the common theme of transiently stable multi-neuronal activity patterns. We followed three leading questions: i) How are selected neurons entrained by their ensemble, and how are others excluded? Here, we looked at the cellular mechanisms which link single neurons with a group of selected cells, forming a ‘meaningful’ ensemble, (e.g., synaptic plasticity, specific afferent or efferent connectivity, subcellular specializations). ii) What are the characteristic features of spatio-temporal activity patterns in different networks? We monitored multi-neuronal dynamics in different models and contexts, revealing common principles and characteristic differences (e.g., sparseness, pattern separation, temporal and spatial characteristics). These properties set important boundary conditions for the emerging systemic functions. iii) How do ensembles adapt to novel experience and to changes of inner or outer conditions? We explored adaptive and state-dependent plasticity of ensembles, a fundamental condition for successful behaviour (e.g. learning-related formation of new ensembles, effects of neuromodulators on the activation of ensembles). These systematic questions are linked by important ‘perpendicular’ motives stretching through all three system levels: What are the links between co-activity at different time scales? How does the structure of cells and networks support function? In order to tackle these questions we used and improved state-of-the-art or even new methods for monitoring, manipulating, detecting and mapping functional ensembles.

Publications

• (2015) Losing control: excessive alcohol seeking after selective inactivation of cue-responsive neurons in the infralimbic cortex. J Neurosci 35:10750-10761
  Pfarr S, Meinhardt MW, Klee ML, Hansson AC, Vengeliene V, Schönig K, Bartsch D, Hope BT, Spanagel R, Sommer WH
  (See online at https://doi.org/10.1523/jneurosci.0684-15.2015)
• (2016) A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron 89:1291-1304
  Eliava M, Melchior M, Knobloch-Bollmann HS, Wahis J, da Silva Gouveia M, Tang Y, Ciobanu AC, Triana del Rio R, Roth LC, Althammer F, Chavant V, Goumon Y, Gruber T, Petit-Demoulière N, Busnelli M, Chini B, Tan LL, Mitre M, Froemke RC, Chao MV, Giese G, Sprengel R, Kuner R, Poisbeau P, Seeburg PH, Stoop R, Charlet A, Grinevich V
  (See online at https://doi.org/10.1016/j.neuron.2016.01.041)
• (2016) Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence. Proc Natl Acad Sci U S A 113:3024-3029
  Hirth N, Meinhardt MW, Noori HR, Salgado H, Torres-Ramirez O, Uhrig S, Broccoli L, Vengeliene V, Roßmanith M, Perreau-Lenz S, Köhr G, Sommer WH, Spanagel R, Hansson AC
  (See online at https://doi.org/10.1073/pnas.1506012113)
• (2016) Differential effects of oxytocin on mouse hippocampal oscillations in vitro. Eur J Neurosci 44:2885-2898
  Maier P, Kaiser ME, Grinevich V, Draguhn A, Both M
  (See online at https://doi.org/10.1111/ejn.13412)
• (2016) Downstream effects of hippocampal sharp wave ripple oscillations on medial entorhinal cortex layer V neurons in vitro. Hippocampus 26:1493-1508
  Roth FC, Beyer KM, Both M, Draguhn A, Egorov AV
  (See online at https://doi.org/10.1002/hipo.22623)
• (2016) Hippocampal offline reactivation consolidates recently formed cell assembly patterns during sharp wave-ripples. Neuron 92:968-974
  van de Ven GM, Trouche S, McNamara CG, Allen K, Dupret D
  (See online at https://doi.org/10.1016/j.neuron.2016.10.020)
• (2016) Oxytocin enhances social recognition by modulating cortical control of early olfactory processing. Neuron 90:609-621
  Oettl LL, Ravi N, Schneider M, Scheller MF, Schneider P, Mitre M, da Silva Gouveia M, Froemke RC, Chao MV, Young WS, Meyer-Lindenberg A, Grinevich V, Shusterman R, Kelsch W
  (See online at https://doi.org/10.1016/j.neuron.2016.03.033)
• (2016) Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex. Nat Neurosci 197:935-944
  Leitner FC, Melzer S, Lütcke H, Pinna R, Seeburg PH, Helmchen F, Monyer H
  (See online at https://doi.org/10.1038/nn.4303)
• (2016) Visual landmarks sharpen grid cell metric and confer context specificity to neurons of the medial entorhinal cortex. Elife 5. pii: e16937
  Pérez-Escobar JA, Kornienko O, Latuske P, Kohler L, Allen K
  (See online at https://doi.org/10.7554/elife.16937)
• (2017) A state space approach for piecewise-linear recurrent neural networks for identifying computational dynamics from neural measurements. PLoS Comput Biol 13:e1005542
  Durstewitz D
  (See online at https://doi.org/10.1371/journal.pcbi.1005542)
• (2017) Cell assemblies at multiple time scales with arbitrary lag constellations. Elife 6
  Russo E, Durstewitz D
  (See online at https://doi.org/10.7554/elife.19428)
• (2017) Deletion of aquaporin-4 curtails extracellular glutamate elevation in cortical spreading depression in awake mice. Cereb Cortex 27:24-33
  Enger R, Dukefoss DB, Tang W, Pettersen KH, Bjørnstad DM, Helm PJ, Jensen V, Sprengel R, Vervaeke K, Ottersen OP, Nagelhus EA
  (See online at https://doi.org/10.1093/cercor/bhw359)
• (2017) Distinct corticostriatal GABAergic ceurons modulate striatal output neurons and motor activity. Cell Rep 195:1045-1055
  Melzer S, Gil M, Koser DE, Michael M, Huang KW, Monyer H
  (See online at https://doi.org/10.1016/j.celrep.2017.04.024)
• (2017) Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus. J Cereb Blood Flow Metab.
  Schneider J, Berndt N, Papageorgiou IE, Maurer J, Bulik S, Both M, Draguhn A, Holzhütter HG, Kann O
  (See online at https://doi.org/10.1177/0271678x17740091)
• (2017) Multiplexed spike coding and adaptation in the thalamus. Cell Rep 19:1130-1140
  Mease RA, Kuner T, Fairhall AL, Groh A
  (See online at https://doi.org/10.1016/j.celrep.2017.04.050)
• (2017) One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength inactivity-dependent transcription in hippocampal neurons. Cell Calcium 65:14-21
  Yu Y, Oberlaender K, Bengtson CP, Bading H
  (See online at https://doi.org/10.1016/j.ceca.2017.03.003)
• (2017) Oxytocin Mobilizes Midbrain Dopamine toward Sociality. Neuron 95:235-237
  Charlet A, Grinevich V
  (See online at https://doi.org/10.1016/j.neuron.2017.07.002)
• (2017) Persistent strengthening of the prefrontal cortex - nucleus accumbens pathway during incubation of cocaine-seeking behavior. Neurobiol Learn Mem 138:281-290
  Luís C, Cannella N, Spanagel R, Köhr G
  (See online at https://doi.org/10.1016/j.nlm.2016.10.003)
• (2017) Selective entrainment of gamma subbands by different slow network oscillations. Proc Natl Acad Sci U S A 114:4519-4524
  Zhong W, Ciatipis M, Wolfenstetter T, Jessberger J, Müller C, Ponsel S, Yanovsky Y, Brankačk J, Tort ABL, Draguhn A
  (See online at https://doi.org/10.1073/pnas.1617249114)
• (2017) Sparse convolutional coding for neuronal assembly detection. NIPS 2017:1-11
  Peter S, Kirschbaum E, Both M, Campbell LA, Harvey BK, Heins C, Durstewitz D, Diego Andilla F, Hamprecht FA
  
• (2017) Structural plasticity of synaptopodin in the axon initial segment during visual cortex development. Cereb Cortex 27:4662-4675
  Schlüter A, Del Turco D, Deller T, Gutzmann A, Schultz C, Engelhardt M
  (See online at https://doi.org/10.1093/cercor/bhx208)
• (2017) The Action Radius of Oxytocin Release in the Mammalian CNS: From Single Vesicles to Behavior. Trends Pharmacol Sci 38:982-991
  Chini B, Verhage M, Grinevich V
  (See online at https://doi.org/10.1016/j.tips.2017.08.005)
• (2018) Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb. eNeuro 5(3)
  Oboti L, Russo E, Tran T, Durstewitz D, Corbin JG
  (See online at https://doi.org/10.1523/eneuro.0175-18.2018)
• (2018) Choice for Drug or Natural Reward Engages Largely Overlapping Neuronal Ensembles in the Infralimbic Prefrontal Cortex. J Neurosci 38:3507-3519
  Pfarr S, Schaaf L, Reinert JK, Paul E, Herrmannsdörfer F, Roßmanith M, Kuner T, Hansson AC, Spanagel R, Körber C, Sommer WH
  (See online at https://doi.org/10.1523/jneurosci.0026-18.2018)
• (2018) CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus. Nat Commun 9:261
  Chen X, Aslam M, Gollisch T, Allen K, von Engelhardt J
  (See online at https://doi.org/10.1038/s41467-017-02415-1)
• (2018) Dnmt3a2 in the nucleus accumbens shell is required for reinstatement of cocaine seeking. J Neurosci 38:7516-7528
  Cannella N, Oliveira A, Hemstedt TJ, Lissek T, Buechler E, Bading H, Spanagel R
  (See online at https://doi.org/10.1523/jneurosci.0600-18.2018)
• (2018) Impaired path integration in mice with disrupted grid cell firing. Nat Neurosci 21:81-91
  Gil M, Ancau M, Schlesiger MI, Neitz A, Allen K, De Marco RJ, Monyer H
  (See online at https://doi.org/10.1038/s41593-017-0039-3)
• (2018) Interplay between Oxytocin and Sensory Systems in the Orchestration of Socio-Emotional Behaviors. Neuron 99(5):887-904
  Grinevich V, Stoop R
  (See online at https://doi.org/10.1016/j.neuron.2018.07.016)
• (2018) Non-rhythmic head-direction cells in the parahippocampal region are not constrained by attractor network dynamics. Elife. 2018
  Kornienko O, Latuske P, Bassler M, Kohler L, Allen K
  (See online at https://doi.org/10.7554/elife.35949)
• (2018) Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol Dependent Rats and Humans. Neuropsychopharmacology. 43(6):1235-1246.
  Hansson AC, Koopmann A, Uhrig S, Bühler S, Domi E, Kiessling E, Ciccocioppo R, Froemke RC, Grinevich V, Kiefer F, Sommer WH, Vollstädt-Klein S, Spanagel R
  (See online at https://doi.org/10.1038/npp.2017.257)
• (2018) Oxytocin Signaling in the Lateral Septum Prevents Social Fear during Lactation. Curr Biol. 28(7):1066-1078.e6
  Menon R, Grund T, Zoicas I, Althammer F, Fiedler D, Biermeier V, Bosch OJ, Hiraoka Y, Nishimori K, Eliava M, Grinevich V, Neumann ID
  (See online at https://doi.org/10.1016/j.cub.2018.02.044)
• (2018) Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons. J Physiol 596(21):5237-5249
  Thome C, Roth FC, Obermayer J, Yanez A, Draguhn A, Egorov AV
  (See online at https://doi.org/10.1113/jp276720)
• (2018) Target selectivity of septal cholinergic neurons in the medial and lateral entorhinal cortex. Proc Natl Acad Sci U S A 115(11):E2644-E2652
  Desikan S, Koser DE, Neitz A, Monyer H
  (See online at https://doi.org/10.1073/pnas.1716531115)
• (2019) A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System. Neuron 103:133-146
  Hasan MT, Althammer F, Silva da Gouveia M, Goyon S, Eliava M, Lefevre A, Kerspern D, Schimmer J, Raftogianni A, Wahis J, Knobloch-Bollmann HS, Tang Y, Liu X, Jain A, Chavant V, Goumon Y, Weislogel JM, Hurlemann R, Herpertz SC, Pitzer C, Darbon P, Dogbevia GK, Bertocchi I, Larkum ME, Sprengel R, Bading H, Charlet A, Grinevich V
  (See online at https://doi.org/10.1016/j.neuron.2019.04.029)
• (2019) Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat Commun 10:983
  Tan LL, Oswald MJ, Heinl C, Retana Romero OA, Kaushalya SK, Monyer H, Kuner R
  (See online at https://doi.org/10.1038/s41467-019-08873-z)
• (2019) Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations. J Cereb Blood Flow Metab. Dec 16
  Elzoheiry S, Lewen A, Schneider J, Both M, Hefter D, Boffi JC, Hollnagel JO, Kann O
  (See online at https://doi.org/10.1177/0271678x19892657)
• (2019) Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice. Curr Biol 29:1938-1953
  Ferretti V, Maltese F, Contarini G, Nigro M, Bonavia A, Huang H, Gigliucci V, Morelli G, Scheggia D, Managò F, Castellani G, Lefevre A, Cancedda L, Chini B, Grinevich V, Papaleo F
  (See online at https://doi.org/10.1016/j.cub.2019.04.070)
• (2019) The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms. J Cereb Blood Flow Metab. Epub 2019 Nov 13
  Bas-Orth C, Schneider J, Lewen A, McQueen J, Hasenpusch-Theil K, Theil T, Hardingham GE, Bading H, Kann O
  (See online at https://doi.org/10.1177/0271678x19887777)
• (2019) TRPC channels are not required for graded persistent activity in entorhinal cortex neurons. Hippocampus 29:1038-1048
  Egorov AV, Schumacher D, Medert R, Birnbaumer L, Freichel M, Draguhn A
  (See online at https://doi.org/10.1002/hipo.23094)
• (2020) A novel method using ambient glutamate for the electrophysiological quantification of extrasynaptic NMDA receptor function in acute brain slices. J Physiol 598:633-650
  Moldavski A, Behr J, Bading H, Bengtson CP
  (See online at https://doi.org/10.1113/jp278362)