Candela Sánchez-Bellot, Rawan AlSubaie,# Karyna Mishchanchuk,# Ryan W. S. Wee, and Andrew F. MacAskillcorresponding author


"Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London, WC1E 6BT UK
Andrew F. MacAskill, Email: [email protected]
corresponding authorCorresponding author.
#Contributed equally."




"The decision to either approach or avoid a potentially threatening environment is thought to rely upon the coordinated activity of heterogeneous neural populations in the hippocampus and prefrontal cortex (PFC). However, how this circuitry is organized to flexibly promote both approach or avoidance at different times has remained elusive. Here, we show that the hippocampal projection to PFC is composed of two parallel circuits located in the superficial or deep pyramidal layers of the CA1/subiculum border. These circuits have unique upstream and downstream connectivity, and are differentially active during approach and avoidance behaviour. The superficial population is preferentially connected to widespread PFC inhibitory interneurons, and its activation promotes exploration; while the deep circuit is connected to PFC pyramidal neurons and fast spiking interneurons, and its activation promotes avoidance. Together this provides a mechanism for regulation of behaviour during approach avoidance conflict: through two specialized, parallel circuits that allow bidirectional hippocampal control of PFC.

Subject terms: Neural circuits, Inhibition-excitation balance

DOI: 10.1038/s41467-022-27977-7


Wide-field illumination was achieved via a 40 x objective with brief (0.2, 0.5, 1, 2 and 5 ms) pulses of blue light from an LED centred at 473 nm (CoolLED pE-4000, with appropriate excitation-emission filters).

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The pE-4000 Universal Illumination System offers 16 selectable wavelengths from 365 - 770 nm, making it a highly flexible illuminator covering a wide variety of fluorophores

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Nature Communications

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