Talk by Norbert Hajos, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary and Francesco Ferraguti, Dept. Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

2019.11.20 | Frederikke Bessermann Hansen

Cortical Inhibitory Microcircuits for Aversive Learning

Francesco Ferraguti

Dept. Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria

The influence of cortical GABAergic inhibitory networks on aversive learning and other emotional valence-related behaviours has received increasing attention in recent years. However, the neural circuits responsible for the link between sensory experience with emotional valence and the exact mechanisms through which inhibitory circuits impact detection and learning of salient/novelty-driven events, are still largely unexplored. Salient event can either carry negative or positive information and their detection facilitates learning and survival. The basolateral amygdala (BLA) is a cortical-like structure known to be involved in highly adaptive forms of emotional learning necessary for survival. Local plasticity of excitatory projection neurons (PNs) in the BLA is considered to be crucial for fear learning. BLA GABAergic interneurons (INs) tightly regulate PNs excitability, however, little is known about their contribution to fear memory formation. BLA INs are highly heterogenous in their neurochemical, physiological and anatomical features. Most IN subtypes target distinct plasma membrane domains of PNs. A distinct subset of INs expressing the vasoactive intestinal polypeptide (VIP) selectively innervate other INs leading to disinhibition of PNs. Using fear conditioning as a model for associative learning, we found that salient stimuli cause learning by recruiting VIP-expressing INs. By means of calcium imaging and optogenetics in freely behaving mice, we demonstrate that BLA VIP-expressing INs are strongly activated by aversive events during associative fear learning and that they provide an instructive signal necessary for associative learning. Notably, BLA VIP-expressing IN responses are plastic and shift from instructive to predictive cues upon memory formation. Furthermore, using a mono-trans-synaptic retrograde tracing approach, we identified direct inputs to these INs from brain areas involved in sensory-emotional processing and delivery of aversive information.

Another brain area responsible for multisensory integration, emotional valence attribution and detection of saliency is the insular cortex (InsCx). We have, therefore, explored whether InsCx VIP-expressing INs are also implicated in the detection of negative salient stimuli necessary for adaptive behaviour. By means of in vivo optogenetic loss-of-function experiments, we have found that inhibition of InsCx VIP-expressing INs during the presentation of foot shocks, in a cued fear conditioning paradigm, prevented retrieval of the fear memory.

Therefore, adaptive gating by VIP interneurons might be a general operational principle that allows to discriminate important from irrelevant sensory stimuli and to facilitate stimulus-associations to ensure appropriate behavioural adaptations to salient events. 

Norbert Hajos, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

Title. Excitement in amygdala circuits caused by noxious stimuli

Abstract. Amygdala refers to a complex region composed of at least 13 functionally distinct nuclei. Of these, the lateral and basal nuclei are cortical structures based on the neuron types, connectivity and developmental characteristics. In this lecture, I will first summarize our recent data about the GABAergic interneuron types and their ratios within the lateral and basal amygdala. Then, I will focus on those amygdalar inhibitory interneurons that potently control the principal neuron spiking via innervating their perisomatic region. Lastly, I will present unpublished results showing how noxious stimuli alter spiking of neurons in these two amygdala nuclei. These latter findings prompted us to propose a novel model for information flow within the amygdala circuits.

Bio-sketch. Norbert Hájos received MSc in biology at Eotvos Lorand University, Budapest (Hungary) in 1994. After finishing the university studies, he received PhD under the supervision of Tamás F. Freund at the Institute of Experimental Medicine, Hungarian Academy of Sciences, in Budapest in 1998. During his doctoral studies, Hájos gained deep knowledge in neuroanatomical techniques, including light and electron microscopy and tracing techniques. After completing the work for the thesis, he joined István Mody’s lab at UCLA, CA to learn in vitro electrophysiological techniques, including single channel recordings and synaptic response measurements obtained in acute slice preparations. When Hájos returned to the Institute of Experimental Medicine in Budapest, his research focused on cannabinoid signaling and rhythm generation in neural networks. In 2009, he established an independent research group, the Laboratory of Network Neurophysiology within the Institute of Experimental Medicine, Budapest with the help of the Wellcome Trust International Senior Research Fellowship. The goal of the lab is to understand how defined neuronal populations contribute to circuit functions. To this end, cutting-edge techniques (optogenetics, viral tracing, in vivo electrophysiological recordings) are combined with in vitro electrophysiological and neuroanatomical methods to address these complex questions. Hájos’s research focuses primary on cellular and microcircuit processes to elucidate the principles of neural communication in cortical structures, including the basolateral amygdala and prefrontal cortex.