Long-range connections of neurons determine their behavioral roles

Together with former co-workers from Basel, Johannes Letzkus (since September 2013 working as a Max Planck Research Group Leader at the Max Planck Institute for Brain Research) investigated the mechanisms of fear learning and extinction. Using electrophysiology and optogenetics, the team found that amygdala neurons sending information to different downstream target areas have opposite roles in memory formation. These results are among the first to demonstrate that - although intermingled locally- the long-range connectivity of neurons determines their behavioral function.

Although ascribed to olfaction in the thirties, it is clear since around 1952 that the amygdala, named after its almond-like shape, plays a crucial role in fear and emotion. Furthermore, it is nowadays clear that complex neural processes critically depend on long-range interactions between different brain areas. The nature and specificity of these interactions is however not well understood. Johannes Letzkus and colleagues investigated the role of two specific populations of neurons in the basal amygdala, defined by connections to different subdivisions of the distant medial prefrontal cortex.

They found in mice that the two different types of neurons are activated in opposite states of fear: In the case of high fear, neurons projecting to the prelimbic subdivision are recruited, whereas fear extinction selectively activates amygdala neurons sending information to the infralimbic part of the prefrontal cortex. What´s more, the team could show that optogenetic activation of the two populations promotes states of high and low fear, respectively. Letzkus: "These results are even more amazing if you consider that the different types of neurons are intermingled in a salt-and-pepper fashion in the amygdala. It is likely that local interactions between the two neuron types enables the animal to switch rapidly between states of high and low fear".