Neural circuits of safety learning

• Applicant: Nadine Gogolla, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391081777

A central endeavour of modern neuroscience is to understand the neural basis of learning and how the selection of distinct circuits modulates experience-dependent changes in behaviour. Decades of research allowed a global understanding of the computations occurring in hard-wired networks during associative learning, in particular fear behaviour. While recent technical advances in neuronal circuit mapping and manipulation have allowed the dissection of the neuronal circuitry mediating fear behaviour in great detail, much less is known about the neuronal mechanisms mediating learned safety: the learning about the non-contingency of safety cues with harmful outcomes. At the circuit level, the neuronal elements involved in safety learning are much less understood. One essential part of the safety network is the posterior part of the insular cortex. Several studies in rodents demonstrate that physical lesions or pharmacological inactivation of the insula prevent learning of safety signals in different paradigms. Next to the insular cortex, also the amygdala and medial prefrontal cortex play important roles in learned safety as shown with electrophysiological recordings. While it has become increasingly clear that neuronal circuits mediating fear and safety learning overlap, it is not understood, how the brain learns about safety. In particular, while fear associations require the coincidence of the aversive event and a neural conditioned stimulus, the opposite is true for safety learning, which relies on the explicit temporal separation of a neutral stimulus and the aversive event. Thus, it is of strong interest to understand how learning of the CS-/US non-contingency is represented and how the regions implicated in safety associations impinge onto fear circuits to inhibit fear behaviour? In this proposal we will use a multidisciplinary approach combining a wide range of techniques aimed at addressing this question at multiple levels. Behaviourally, we will use a model in which two different conditioned stimulus are associated with opposite behavioural responses (fear vs safety responses). This will provide a quantitative framework for identifying the neurobiological underpinnings with increasing degrees of resolution from local oscillations to single unit recordings, calcium imaging and tracing of inputs and outputs. Our recordings will focus on identifying cell assemblies nested within insular cortex oscillations and their modulation by local inhibitory networks. Unprecedented optogenetic manipulations of oscillations and cell assemblies will establish a causal link between the emergence of specific oscillatory patterns, circuit selection through the formation of assemblies and appropriate fear responses.

• DFG Programme: Research Grants
• International Connection: France
• Partner Organisation: Agence Nationale de la Recherche / The French National Research Agency
• Cooperation Partner: Cyril Herry, Ph.D.