Johannes J. Letzkus (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland)

The Bernstein Center Freiburg

Bernstein Seminar

Johannes J. Letzkus

Friedrich Miescher Institute for Biomedical Research
Basel, Switzerland

 

A disinhibitory microcircuit for associative
fear learning in auditory cortex

Abstract:
Memory formation is one of the most fundamental brain functions. While synaptic plasticity as the putative cellular mechanism of learning has been studied in great detail, we know much less about how interactions between different types of neurons within local circuits contribute to memory formation. To address this question, we recorded activity in identified neurons in auditory cortex during foot-shocks, which drive formation of associative fear memory when coinciding with tones. Two-photon calcium imaging and targeted patch-clamp recordings in anaesthetized mice indicate that foot-shocks activate cholinergic projections from the basal forebrain, thereby recruiting a disinhibitory microcircuit in the superficial layers of auditory cortex. Disinhibition of pyramidal neurons in turn strongly enhanced processing of auditory stimuli, potentially gating activity-dependent synaptic plasticity either locally or in downstream target areas. Importantly, counteracting the observed disinhibition of auditory cortex exclusively during and after the foot-shock by optogenetic means leads to almost complete block of fear memory formation in behaving mice, suggesting that this microcircuit is required for associative learning.

Host: Marlene Bartos