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Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray

Abstract

A form of aversively motivated learning called fear conditioning occurs when a neutral conditioned stimulus is paired with an aversive unconditioned stimulus (UCS). UCS-evoked depolarization of amygdala neurons may instruct Hebbian plasticity that stores memories of the conditioned stimulus–unconditioned stimulus association, but the origin of UCS inputs to the amygdala is unknown. Theory and evidence suggest that instructive UCS inputs to the amygdala will be inhibited when the UCS is expected, but this has not been found during fear conditioning. We investigated neural pathways that relay information about the UCS to the amygdala by recording neurons in the amygdala and periaqueductal gray (PAG) of rats during fear conditioning. UCS-evoked responses in both amygdala and PAG were inhibited by expectation. Pharmacological inactivation of the PAG attenuated UCS-evoked responses in the amygdala and impaired acquisition of fear conditioning, indicating that PAG may be an important part of the pathway that relays instructive signals to the amygdala.

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Figure 1: Activity of LAn neurons during acquisition of fear conditioning.
Figure 2: LAn/basal neurons responded more to unsignaled (unsig) than signaled (sig) shocks.
Figure 3: Attenuation of shock-evoked responding in LAn neurons by PAG inactivation.
Figure 4: Effects of PAG inactivation on fear conditioning.
Figure 5: Activity of PAG neurons during acquisition of fear conditioning.
Figure 6: PAG neurons responded more to unsignaled than to signaled shocks.

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Acknowledgements

We are grateful to S. Nicola and A. Welday for comments on an earlier version of the manuscript and M. Fanselow, D. Buonomano, R. Thompson, D. Schiller and Y. Niv for valuable discussions. This work was supported by a National Science Foundation Graduate Research Fellowship to J.P.J. and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award and US National Institutes of Health grant (R01 MH073700-01) to H.T.B.

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All authors contributed to the planning and design of the study. Data collection was performed by J.P.J. and J.W.T. Data analysis and writing of the manuscript were performed by J.P.J., J.W.T. and H.T.B. The neurophysiology and fear conditioning experiments were conducted in the laboratory of H.T.B. and the blocking experiments were conducted in the laboratory of J.E.L.

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Correspondence to Jason W Tarpley or Hugh T Blair.

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The authors declare no competing financial interests.

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Johansen, J., Tarpley, J., LeDoux, J. et al. Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat Neurosci 13, 979–986 (2010). https://doi.org/10.1038/nn.2594

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