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HomeNaturePrefrontal encoding of an internal model for emotional inference

Prefrontal encoding of an internal model for emotional inference

  • Herry, C. & Johansen, J. P. Encoding of fear learning and memory in distributed neuronal circuits. Nat. Neurosci. 17, 1644–1654 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Janak, P. H. & Tye, K. M. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tovote, P., Fadok, J. P. & Lüthi, A. Neuronal circuits for fear and anxiety. Nat. Rev. Neurosci. 16, 317–331 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Malezieux, M., Klein, A. S. & Gogolla, N. Neural circuits for emotion. Annu. Rev. Neurosci. 46, 211–231 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • LeDoux, J. E. What emotions might be like in other animals. Curr. Biol. 31, R824–R829 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barrett, L. F., Mesquita, B., Ochsner, K. N. & Gross, J. J. The experience of emotion. Annu. Rev. Psychol. 58, 373–403 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Phelps, E. A. & LeDoux, J. E. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48, 175–187 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • LeDoux, J. & Daw, N. D. Surviving threats: neural circuit and computational implications of a new taxonomy of defensive behaviour. Nat. Rev. Neurosci. 19, 269–282 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Poon, C.-S. & Merfeld, D. M. Internal models: the state of the art. J. Neural Eng. 2, E01 (2005).

    Article 

    Google Scholar
     

  • Ito, M. Control of mental activities by internal models in the cerebellum. Nat. Rev. Neurosci. 9, 304–313 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Balleine, B. W., Dezfouli, A., Ito, M. & Doya, K. Hierarchical control of goal-directed action in the cortical–basal ganglia network. Curr. Opin. Behav. Sci. 5, 1–7 (2015).

    Article 

    Google Scholar
     

  • Wikenheiser, A. M. & Schoenbaum, G. Over the river, through the woods: cognitive maps in the hippocampus and orbitofrontal cortex. Nat. Rev. Neurosci. 17, 513–523 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Imamizu, H. & Kawato, M. Neural correlates of predictive and postdictive switching mechanisms for internal models. J. Neurosci. 28, 10751–10765 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gershman, S. J. & Niv, Y. Learning latent structure: carving nature at its joints. Curr. Opin. Neurobiol. 20, 251–256 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sadacca, B. F. et al. Orbitofrontal neurons signal sensory associations underlying model-based inference in a sensory preconditioning task. eLife 7, e30373 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hart, E. E., Gardner, M. P. H. & Schoenbaum, G. Anterior cingulate neurons signal neutral cue pairings during sensory preconditioning. Curr. Biol. 32, 725–732.e3 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miyashita, Y. Cognitive memory: cellular and network machineries and their top-down control. Science 306, 435–440 (2004).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Holmes, N. M., Parkes, S. L., Killcross, A. S. & Westbrook, R. F. The basolateral amygdala is critical for learning about neutral stimuli in the presence of danger, and the perirhinal cortex is critical in the absence of danger. J. Neurosci. 33, 13112–13125 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baeg, E. H. et al. Dynamics of population code for working memory in the prefrontal cortex. Neuron 40, 177–188 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matsumoto, K., Suzuki, W. & Tanaka, K. Neuronal correlates of goal-based motor selection in the prefrontal cortex. Science 301, 229–232 (2003).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Euston, D. R., Gruber, A. J. & McNaughton, B. L. The role of medial prefrontal cortex in memory and decision making. Neuron 76, 1057–1070 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morrissey, M. D., Insel, N. & Takehara-Nishiuchi, K. Generalizable knowledge outweighs incidental details in prefrontal ensemble code over time. eLife 6, e22177 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Simon, J., Rudebeck, P. H. & Rich, E. L. From affective to cognitive processing: functional organization of the medial frontal cortex. Int. Rev. Neurobiol. 158, 1–28 (2021).

  • Tse, D. et al. Schema-dependent gene activation and memory encoding in neocortex. Science 333, 891–895 (2011).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Klein-Flügge, M. C., Wittmann, M. K., Shpektor, A., Jensen, D. E. A. & Rushworth, M. F. S. Multiple associative structures created by reinforcement and incidental statistical learning mechanisms. Nat. Commun. 10, 4835 (2019).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bongioanni, A. et al. Activation and disruption of a neural mechanism for novel choice in monkeys. Nature 591, 270–274 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, L. et al. Single-neuron projectome of mouse prefrontal cortex. Nat. Neurosci. 25, 515–529 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takehara-Nishiuchi, K. Flexibility of memory for future-oriented cognition. Curr. Opin. Neurobiol. 76, 102622 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Courtin, J. et al. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression. Nature 505, 92–96 (2014).

    Article 
    ADS 
    PubMed 

    Google Scholar
     

  • Laufer, O., Israeli, D. & Paz, R. Behavioral and neural mechanisms of overgeneralization in anxiety. Curr. Biol. 26, 713–722 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Salzman, C. D. & Fusi, S. Emotion, cognition, and mental state representation in amygdala and prefrontal cortex. Annu. Rev. Neurosci. 33, 173–202 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Likhtik, E., Stujenske, J. M., Topiwala, M. A., Harris, A. Z. & Gordon, J. A. Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety. Nat. Neurosci. 17, 106–113 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Burgos-Robles, A., Vidal-Gonzalez, I. & Quirk, G. J. Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J. Neurosci. 29, 8474–8482 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jercog, D. et al. Dynamical prefrontal population coding during defensive behaviours. Nature 595, 690–694 (2021).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Cummings, K. A. & Clem, R. L. Prefrontal somatostatin interneurons encode fear memory. Nat. Neurosci. 23, 61–74 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Agetsuma, M. et al. Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation. Nat. Commun. 14, 5996 (2023).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Do-Monte, F. H., Quiñones-Laracuente, K. & Quirk, G. J. A temporal shift in the circuits mediating retrieval of fear memory. Nature 519, 460–463 (2015).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dixsaut, L. & Gräff, J. The medial prefrontal cortex and fear memory: dynamics, connectivity, and engrams. Int. J. Mol. Sci. 22, 12113 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rawson, T., O’Kane, M. & Talk, A. The medial prefrontal cortex and memory of cue location in the rat. Neurobiol. Learn. Mem. 93, 132–136 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Likhtik, E. & Paz, R. Amygdala–prefrontal interactions in (mal)adaptive learning. Trends Neurosci. 38, 158–166 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anastasiades, P. G. & Carter, A. G. Circuit organization of the rodent medial prefrontal cortex. Trends Neurosci. 44, 550–563 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Maren, S. & Quirk, G. J. Neuronal signalling of fear memory. Nat. Rev. Neurosci. 5, 844–852 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Madarasz, T. J. et al. Evaluation of ambiguous associations in the amygdala by learning the structure of the environment. Nat. Neurosci. 19, 965–972 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saez, A., Rigotti, M., Ostojic, S., Fusi, S. & Salzman, C. D. Abstract context representations in primate amygdala and prefrontal cortex. Neuron 87, 869–881 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kyriazi, P., Headley, D. B. & Paré, D. Different multidimensional representations across the amygdalo-prefrontal network during an approach-avoidance task. Neuron 107, 717–730.e5 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Holmes, N. M., Wong, F. S., Bouchekioua, Y. & Westbrook, R. F. Not “either-or” but “which-when”: a review of the evidence for integration in sensory preconditioning. Neurosci. Biobehav. Rev. 132, 1197–1204 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Iordanova, M. D., Burnett, D. J., Aggleton, J. P., Good, M. & Honey, R. C. The role of the hippocampus in mnemonic integration and retrieval: complementary evidence from lesion and inactivation studies. Eur. J. Neurosci. 30, 2177–2189 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bornstein, A. M. & Daw, N. D. Cortical and hippocampal correlates of deliberation during model-based decisions for rewards in humans. PLoS Comput. Biol. 9, e1003387 (2013).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barron, H. C. et al. Neuronal computation underlying inferential reasoning in humans and mice. Cell 183, 228–243.e21 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wimmer, G. E. & Shohamy, D. Preference by association: how memory mechanisms in the hippocampus bias decisions. Science 338, 270–273 (2012).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Jun, H. et al. Prefrontal and lateral entorhinal neurons co-dependently learn item–outcome rules. Nature 633, 864–871 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rizley, R. C. & Rescorla, R. A. Associations in second-order conditioning and sensory preconditioning. J. Comp. Physiol. Psychol. 81, 1–11 (1972).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gostolupce, D., Lay, B. P. P., Maes, E. J. P. & Iordanova, M. D. Understanding associative learning through higher-order conditioning. Front. Behav. Neurosci. 16, 845616 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghosh, K. K. et al. Miniaturized integration of a fluorescence microscope. Nat. Methods 8, 871–878 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Courtin, J. et al. A neuronal mechanism for motivational control of behavior. Science 375, eabg7277 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wheeler, D. S., Sherwood, A. & Holland, P. C. Excitatory and inhibitory learning with absent stimuli. J. Exp. Psychol. Anim. Behav. Process. 34, 247–255 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hall, G. Learning about associatively activated stimulus representations: implications for acquired equivalence and perceptual learning. Anim. Learn. Behav. 24, 233–255 (1996).

    Article 

    Google Scholar
     

  • Yiu, A. P. et al. Neurons are recruited to a memory trace based on relative neuronal excitability immediately before training. Neuron 83, 722–735 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, Y. et al. CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nat. Neurosci. 12, 1438–1443 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cai, D. J. et al. A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534, 115–118 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rashid, A. J. et al. Competition between engrams influences fear memory formation and recall. Science 353, 383–387 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zaki, Y. et al. Offline ensemble co-reactivation links memories across days. Nature 637, 145–155 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mocle, A. J. et al. Excitability mediates allocation of pre-configured ensembles to a hippocampal engram supporting contextual conditioned threat in mice. Neuron 112, 1487–1497.e6 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Johansen, J. P. et al. Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation. Proc. Natl Acad. Sci. USA 111, E5584–E5592 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ozawa, T. et al. A feedback neural circuit for calibrating aversive memory strength. Nat. Neurosci. 20, 90–97 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Holmes, N. M., Fam, J. P., Clemens, K. J., Laurent, V. & Westbrook, R. F. The neural substrates of higher-order conditioning: a review. Neurosci. Biobehav. Rev. 138, 104687 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Carr, M. F., Jadhav, S. P. & Frank, L. M. Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat. Neurosci. 14, 147–153 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aly, M. H., Abdou, K., Okubo-Suzuki, R., Nomoto, M. & Inokuchi, K. Selective engram coreactivation in idling brain inspires implicit learning. Proc. Natl Acad. Sci. USA 119, e2201578119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ormond, J., Serka, S. A. & Johansen, J. P. Enhanced reactivation of remapping place cells during aversive learning. J. Neurosci. 43, 2153–2167 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quirk, G. J., Armony, J. L. & LeDoux, J. E. Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala. Neuron 19, 613–624 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maren, S. & Holmes, A. Stress and fear extinction. Neuropsychopharmacology 41, 58–79 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Milad, M. R. & Quirk, G. J. Fear extinction as a model for translational neuroscience: ten years of progress. Annu. Rev. Psychol. 63, 129–151 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Johansen, J. P., Cain, C. K., Ostroff, L. E. & LeDoux, J. E. Molecular mechanisms of fear learning and memory. Cell 147, 509–524 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Branco, T. & Redgrave, P. The neural basis of escape behavior in vertebrates. Annu. Rev. Neurosci. 43, 417–439 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Anderson, D. J. & Adolphs, R. A framework for studying emotions across species. Cell 157, 187–200 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • LeDoux, J. E. & Pine, D. S. Using neuroscience to help understand fear and anxiety: a two-system framework. Am. J. Psychiatry 173, 1083–1093 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press, 2007).

  • Gründemann, J. et al. Amygdala ensembles encode behavioral states. Science 364, eaav8736 (2019).

    Article 
    PubMed 

    Google Scholar
     

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