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bioRxiv · 10.1101/2022.06.28.497926

Coexisting persistent and dynamic representations of stimulus, time and trial outcome emerge in the hippocampus-prefrontal circuitry during learning of a temporal association

Souza, B. C.·Klee, J. L.·Mazzucato, L.·Battaglia, F. P.
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Abstract

Temporal associations between sensory stimuli separated in time rely on the interaction between the hippocampus and medial prefrontal cortex (mPFC). However, it is not known how changes in their neural activity support the emergence of temporal association learning. Here, we use simultaneous electrophysiological recordings in the hippocampal CA1 region and mPFC of mice to elucidate the neural dynamics underlying memory formation in an auditory trace conditioning task. We found that in both areas conditioned (CS+/CS-) and unconditioned stimuli (US) evoked similar temporal sequences of neural responses that progressively diverged during learning. Additionally, persistent CS representations emerged in mPFC after learning, supported by CS+ coding states whose transient reactivation reliably predicted lick onset and behavioral performance on single trials. These results show that coordination of temporal sequences in CA1 and persistent activity in mPFC may underlie temporal association learning, and that transient reactivations of engrams in mPFC predict the animal behavior. HighlightsO_LITemporal representation of CS+, but not CS- and US, strengthens in CA1 after learning. C_LIO_LISimilarity between stimulus and reward temporal representations decrease with learning, but is recovered in error trials. C_LIO_LIRepresentation of stimulus identity is strong and stable in PFC since stimulus onset, while it only emerges in CA1 during trace period. C_LIO_LINeural states defined on faster time-scales reveal the emergence of CS coding states in PFC whose onset predicts lick times and task performance. C_LIO_LIPFC-CA1 states do not increase coordination during late CS+ stimulus and trace. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/497926v2_fig0.gif" ALT="Figure 0"> View larger version (32K): org.highwire.dtl.DTLVardef@93f7a7org.highwire.dtl.DTLVardef@6804a0org.highwire.dtl.DTLVardef@107a6a2org.highwire.dtl.DTLVardef@14cfb23_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 0:C_FLOATNO Graphical Abstract C_FIG

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Souza, B. C., Klee, J. L., Mazzucato, L., Battaglia, F. P.. 2022-07-03. Coexisting persistent and dynamic representations of stimulus, time and trial outcome emerge in the hippocampus-prefrontal circuitry during learning of a temporal association. https://doi.org/10.1101/2022.06.28.497926

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