SFB 779: Neurobiology of Motivated Behaviour
Final Report Abstract
Motivation is a fundamental determining factor of all goal-oriented behaviour and decision-making in higher animals and humans. Motivation, therefore, is not only an important concept for fundamental research aimed at unravelling the causal basis of behaviour, but is also of highest societal relevance as motivational factors determine the thriving of individuals in the contexts of their private and professional lives, and pathological disturbance of motivational control is at the basis of a significant number of neuropsychiatric diseases. Interestingly, while theories of the nature of motivation have a century-long history in psychology and the social sciences, the systematic exploration of brain mechanisms underlying motivation has begun only relatively recently. Moreover, several different concepts for the nature of motivation and its neuronal basis exist in the literature. The scientific approach taken by the Collaborative Research Centre (CRC) 779 "Neurobiology of motivated behaviour" was to focus on processes of decision-making and its adaptation in the context of learning scenarios. This approach allowed a convergent research program based on both animal research and human research and the full exploitation of the complementary advantages of both, historically separated, research traditions. In an additional related strategic decision, the Collaborative Research Centre has implemented a central behavioural paradigm (the "Integrative Paradigm of the CRC") that allowed researchers from traditionally separated methodological fields, including molecular and cellular neuroscience, circuit and systems neuroscience, and whole-brain imaging, to collaborate on the same experiment. These two strategic decisions proved pivotal for the mutual fostering of research impact in each of the individual fields and a multiplicative effect of the research impact for the consortium as a whole. Based on these strategic decisions, over its three funding periods, the CRC has significantly improved our understanding of the neural basis of motivational control of behaviour. An early focus of the research was on the integration of sensory and affective neuronal processing in the brain. Both, animal and corresponding human research, have provided a deep understanding not only about how sensory information is integrated in motivational control, but also about how sensory processes themselves are already affected by motivational processes. It has been a general feature of the CRC's collaborative work that such new insights were typically associated with a very broad basis linking results from several levels of description, ranging from the molecular/cellular levels, via the circuit and network levels to the level of whole-brain neuroimaging. After the early focus on the sensory-valence relationship, the CRC has then investigated the action-valence relationship, again by carefully designing suitable experiments in animals and humans. The corresponding results have pointed to an unexpectedly high impact of precise timing relationships between local neuronal signals for determining global aspects of behavioural control. These results have paved the way for a new research area that is currently developed in Magdeburg. As a further development, the results on the neural bases of motivational aspects of decision-making and their modulation by cognitive state, age or disease, are currently generalized to acknowledge that cognitive functions in general are based on neural resources that are limited and vulnerable. These insights and developments have now paved the way for a new CRC initiative, currently pursued in Magdeburg, investigating the nature of these resources and interventional strategies to recruit them.
Publications
- (2008) Global vs. local processing of frequency-modulated tones in gerbils: an animal model of lateralized auditory cortex functions in humans. Proc Natl Acad Sci USA 105: 6753-6758
Wetzel W, Ohl FW, Scheich H
(See online at https://doi.org/10.1073/pnas.0707844105) - (2009) Intracortical Microstimulation and its Role for Sensory Processing and Learning. J Neurosci 29: 15898-15909
Deliano M, Scheich H, Ohl FW
(See online at https://doi.org/10.1523/jneurosci.1949-09.2009) - (2010) Differential neuromodulation of acquisition and retrieval of avoidance learning by the lateral habenula and ventral tegmental area. J Neurosci 30: 5876-5883
Shumake J, Ilango A, Scheich H, Wetzel W, Ohl FW
(See online at https://doi.org/10.1523/jneurosci.3604-09.2010) - (2012). Striatal activations signal prediction errors on confidence in the absence of external feedback. NeuroImage, 59, 3457-3467
Daniel, R. & Pollmann, S.
(See online at https://doi.org/10.1016/j.neuroimage.2011.11.058) - 2012. Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents. J Physiol. 590:193-208
Meis, S., T. Endres, V. Lessmann
(See online at https://doi.org/10.1113/jphysiol.2011.220434) - (2013) Nucleus accumbens activity dissociates different forms of salience: evidence from human intracranial recordings. J Neuroscience; 33(20): 8764-71
Zaehle T, Bauch EM, Hinrichs H, Schmitt FC, Voges J, Heinze HJ & Bunzeck N
(See online at https://doi.org/10.1523/JNEUROSCI.5276-12.2013) - (2013). Real and fictive outcomes are processed differently but converge on a common adaptive mechanism. Neuron, 79, 1243–1255
Fischer AG, Ullsperger M
(See online at https://doi.org/10.1016/j.neuron.2013.07.006) - (2014) Bassoon Specifically Controls Presynaptic P/Q-type Ca(2+) Channels via RIM-Binding Protein. Neuron 82: 181-194
Davydova D, Marini C, King C, Klueva J, Bischof F, Romorini S, Montenegro-Venegas C, Heine M, Schneider R, Schröder MS, Altrock WD, Henneberger C, Rusakov DA, Gundelfinger ED, Fejtova A
(See online at https://doi.org/10.1016/j.neuron.2014.02.012) - (2014) Corticothalamic phase synchrony and crossfrequency coupling predict human memory formation. eLife
Sweeney-Reed CM, Zaehle T, Voges J, Schmitt FC, Buentjen L, Kopitzki K, Esslinger C, Hinrichs H, Heinze HJ, Knight RT & Richardson-Klavehn A
(See online at https://doi.org/10.7554/elife.05352) - (2014) Dopamine-modulated recurrent corticoefferent feedback in primary sensory cortex promotes detection of behaviorally relevant stimuli. J Neurosci 34: 1234-1247
Happel MF, Deliano M, Handschuh J, Ohl FW
(See online at https://doi.org/10.1523/jneurosci.1990-13.2014) - (2014) Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex. Proc Natl Acad Sci U S A 111(7):2800-5
Happel MF, Niekisch H, Castiblanco Rivera LL, Ohl FW, Deliano M, Frischknecht R
(See online at https://doi.org/10.1073/pnas.1310272111) - (2014) Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding. Nat Commun 5:5547
Maass A, Schütze H, Speck O, Yonelinas A, Tempelmann C, Heinze HJ, Berron D, Cardenas-Blanco A, Brodersen KH, Stephan KE, Düzel E
(See online at https://doi.org/10.1038/ncomms6547) - (2014). Contribution of emotional and motivational neurocircuitry in cue signaled active avoidance learning. Front. Behav. Neurosci 8: 372
Ilango A, Shumake J, Wetzel W, Ohl FW
(See online at https://doi.org/10.3389/fnbeh.2014.00372) - (2015) Cell-selective labeling of proteomes in Drosophila melano-gaster. Nat Comm 6:7521
Erdmann I, Marter K, Kobler O, Niehues S, Abele J, Müller A, Bussmann J, Storkebaum E, Ziv T, Thomas U, Dieterich DC
(See online at https://doi.org/10.1038/ncomms8521) - (2015) Relief learning is dependent on NMDA receptor activation in the nu-cleus accumbens. Br J Pharmacol 172: 2419-2426
Mohammadi M & Fendt M
(See online at https://doi.org/10.1111/bph.13070) - (2015) Role of cortical neurodynamics for understanding the neural basis of motivated behavior - lessons from auditory category learning. Curr Opin Neurobiol 31:88-94
Ohl FW
(See online at https://doi.org/10.1016/j.conb.2014.08.014) - (2015) Sensory Deviancy Detection measured directly within Human Nucleus Accumbens. Cerebral Cortex 26(3):1168-1175
Dürschmid S, Zaehle T, Hinrichs H, Heinze HJ, Voges J, Garrido M, Dolan R & Knight RT
(See online at https://doi.org/10.1093/cercor/bhu304) - 2015. Synapsin determines memory strength after punishment- and relief-learning. J Neurosci 35, 7487-7502
Niewalda T, Michels B, Jungnickel R, Diegelmann S, Kleber J, Kähne T, Gerber B
(See online at https://doi.org/10.1523/jneurosci.4454-14.2015) - 2015. Theta Burst Firing Recruits BDNF Release and Signaling in Postsynaptic CA1 Neurons in Spike-Timing- Dependent LTP. Neuron. 86:1041-1054
Edelmann, E., E. Cepeda-Prado, M. Franck, P. Lichtenecker, T. Brigadski, V. Lessmann
(See online at https://doi.org/10.1016/j.neuron.2015.04.007) - (2016) Proteomics of the Synapse--A Quantitative Approach to Neuronal Plasticity. Molecular & cellular proteomics : Mol Cell Proteomics 15:368-381
Dieterich DC, Kreutz MR
(See online at https://doi.org/10.1074/mcp.r115.051482) - (2016). Neural structures involved in visual search guidance by reward-enhanced contextual cueing of the target location. NeuroImage, 124, 887-897
Pollmann, S., Eštočinová, J., Sommer, S., Chelazzi, L. & Zinke, W.
(See online at https://doi.org/10.1016/j.neuroimage.2015.09.040) - 2016. Identification of Parvalbumin Interneurons as Cellular Substrate of Fear Memory Persistence. Cereb Cortex 26(5):2325-2340
Çaliskan G, Müller I, Semtner M, Winkelmann A, Raza AS, Hollnagel JO, Rösler A, Heinemann U, Stork O, Meier JC
(See online at https://doi.org/10.1093/cercor/bhw001) - A jacob/nsmf gene knock-out results in hippocampal dysplasia and impaired BDNF signalling in dendritogenesis. PLoS Genet. 2016 12(3):e1005907
Spilker C, Nullmeier S, Grochowska KM, Schumacher A, Butnara I, Macharadze T, Yuanxiang P, Gomes GM, Bayraktar G, Rodenstein C, Kolodziej A, Montag D, Angenstein F, Bär J, D’Hanis W, Ros-koden T, Mikhaylova M, Budinger E, Ohl FW, Stork O, Karpova A, Zenclussen AC, Schwegler H, Kreutz MR
(See online at https://doi.org/10.1371/journal.pgen.1005907) - (2017) Attention to color sharpens neural population tuning via feedback processing in the human visual cortex hierarchy. J Neurosci 37:10346–10357
Bartsch MV, Loewe K, Merkel C, Heinze HJ, Schoenfeld MA, Tsotsos JK, Hopf JM
(See online at https://doi.org/10.1523/jneurosci.0666-17.2017) - (2017) Learning relative values in the striatum induces violations of normative decision making. Nat Commun 8:16033
Klein TA, Ullsperger M, Jocham G
(See online at https://doi.org/10.1038/ncomms16033) - 2017. HIPP neurons in the dentate gyrus mediate the cholinergic modulation of background context memory salience. Nat Commun 8(1):189
Raza SA, Albrecht A, Çalışkan G, Müller B, Demiray YE, Ludewig S, Meis S, Faber N, Hartig R, Schraven B, Less-mann V, Schwegler H, Stork O
(See online at https://doi.org/10.1038/s41467-017-00205-3) - (2018) Cortical mechanisms of prioritizing selection for rejection in visual search. J Neurosci 38:4738–4748
Donohue SE, Bartsch MV, Heinze HJ, Schoenfeld MA, Hopf JM
(See online at https://doi.org/10.1523/jneurosci.2407-17.2018) - (2018) Dopaminergic neuro-modulation of high-gamma stimulus phase-locking in gerbil primary auditory cortex mediated by D1/D5-receptors. Eur J Neurosci.
Deliano M, Brunk MG, El-Tabbal M, Zempeltzi MM, Happel MFK, Ohl FW
(See online at https://doi.org/10.1111/ejn.13898) - (2018) Orbitofrontal signaling of future reward is associated with hyperactivity in attention-deficit/hyperactivity disorder. J Neurosci, 38(30):6779–6786
Tegelbeckers J, Kanowski M, Krauel K, Haynes J-D, Breitling C, Flechtner H-H, Kahnt T
(See online at https://doi.org/10.1523/jneurosci.0411-18.2018) - (2018) Role of the mesolimbic dopamine system in relief learning. Neuropsychopharmacology 43: 1651-1659
Mayer D, Kahl E, Uzuneser TC & Fendt M
(See online at https://doi.org/10.1038/s41386-018-0020-1) - (2018). A GAD65 promoter polymorphism rs2236418 modulates harm avoidance in women via inhibition/excitation balance in the rostral ACC. J Neurosci. 2018 May 30;38(22):5067-5077
Colic L, Li M, Demenescu LR, Li S, Müller I, Richter A, Seidenbecher CI, Speck O, Schott BH, Stork O, Walter M
(See online at https://doi.org/10.1523/jneurosci.1985-17.2018) - (2018). The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3. PLOS biology. PLoS Biol 16(8): e2006100
Beer Z, Vavra P, Atucha E, Rentzing K, Heinze HJ, Sauvage MM
(See online at https://doi.org/10.1371/journal.pbio.2006100) - 2018. Dorsal tegmental dopamine neurons gate associative learning of fear. Nat Neurosci. 21:952-962
Groessl, F., T. Munsch, S. Meis, J. Griessner, J. Kaczanowska, P. Pliota, D. Kargl, S. Badurek, K. Kraitsy, A. Rassoulpour, J. Zuber, V. Lessmann, W. Haubensak
(See online at https://doi.org/10.1038/s41593-018-0174-5) - 2018. The Relation Between Long-Term Synaptic Plasticity at Glutamatergic Synapses in the Amygdala and Fear Learning in Adult Heterozygous BDNF-Knockout Mice. Cereb Cortex. 28:1195-1208
Meis, S., T. Endres, T. Munsch, and V. Lessmann
(See online at https://doi.org/10.1093/cercor/bhx032) - (2019) SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals. Nat Commun 10(1):5448
Andres-Alonso M, Ammar MR, Butnaru I, Gomes GM, Acuña Sanhueza G, Raman R, Yuanxiang P, Borgmeyer M, Lopez-Rojas J, Raza SA, Brice N, Hausrat TJ, Macharadze T, Diaz-Gonzalez S, Carlton M, Failla AV, Stork O, Schweizer M, Gundelfinger ED, Kneussel M, Spilker C, Karpova A, Kreutz MR
(See online at https://doi.org/10.1038/s41467-019-13224-z) - (2019) β‐adrenergic modulation of discrimination learning and memory in the auditory cortex. Eur J Neurosci 50:3141-3163
Schicknick H, Henschke JU, Budinger E, Ohl FW, Gundelfinger ED, Tischmeyer W
(See online at https://doi.org/10.1111/ejn.14480) - 2019 Timing-dependent valence reversal: A principle of reinforcement processing and its possible implications. Curr Op Behav Sci, 26, 114-120
Gerber B, König C, Fendt M, Andreatta M, Romanos M, Pauli P, Yarali A
(See online at https://doi.org/10.1016/j.cobeha.2018.12.001) - 2019. Learning Induces Transient Upregulation of Brevican in the Auditory Cortex during Consolidation of Long-Term Memories. J Neurosci. 2019 Sep 4;39(36):7049-7060
Niekisch H, Steinhardt J, Berghäuser J, Bertazzoni S, Kaschinski E, Kasper J, Kisse M, Mitlöhner J, Singh JB, Weber J, Frischknecht R, Happel MFK
(See online at https://doi.org/10.1523/jneurosci.2499-18.2019) - (2020) Dopamine receptor activation modulates the integrity of the perisynaptic extracellular matrix at excitatory synapses. Cells 9(2), pii:E260
Mitlöhner J, Kaushik R, Niekisch H, Blondiaux A, Gee CE, Happel MFK, Gundelfinger E, Dityatev A, Frischknecht R, Seidenbecher C
(See online at https://doi.org/10.3390/cells9020260) - (2020) Electroencephalography reveals a selective disruption of cognitive control processes in craving cigarette smokers. Eur J Neurosci. 2020 Feb;51(4):1087-1105
Donohue SE, Harris JA, Loewe K, Hopf JM, Heinze HJ, Woldorff MG, Schoenfeld MA
(See online at https://doi.org/10.1111/ejn.14622) - Macroscopic information-based taste representations in insular cortex are shaped by stimulus concentration. Proceeding of the National Academy of Sciences
Porcu E, Benz KM, Ball F, Tempelmann C, Hanke M, Noesselt T
(See online at https://doi.org/10.1073/pnas.1916329117)
