Neuronal circuits of the ventral CA1 hippocampus and anxiety

Anxiety is an emotional experience that prevails in anticipation of potential threats. Thus, anxiety serves as an important alert signal to avoid and recognize potential dangers, but unbalanced anxiety levels have a major impact on the quality of life. Anxiety is thought to be reflected in neuronal circuits involving several brain areas including the hippocampus, prefrontal cortex and amygdala. Recently we have identified neuronal correlates of anxiety in the firing patterns of neurons in the ventral CA1 hippocampus. We have identified neurons which increase their activity at places which are associated with increased levels of anxiety like exposed and unsecured, elevated platforms. In the present project we aim to determine how these activity patterns of hippocampal neurons evolve from the first encounter of an anxiogenic situation to the habituation and familiarization of such an experience. For this we will record the activity of neurons in the ventral CA1 hippocampus during the free decision to explore an anxiogenic location as well as when a familiar and previously safe location is suddenly turned into a potentially dangerous environment. We will test the hypothesis that firing patterns in the hippocampus reflect not only the first encounter of an anxious situation but these firing patterns also subside together with the habituation and familiarization of the potentially dangerous environment. Furthermore we will use optogenetic manipulation of neuronal activity in the ventral hippocampus and we will test whether such manipulation can alter the anxiety-related behaviour and risk taking. In another set of experiments we will investigate the downstream processing of neuronal signalling in the ventral CA1 hippocampus. I particular, we will determine how neurons in the prefrontal cortex receive anxiety-related information from the hippocampus, how this information in proicess further and to which oterh brain regions anxiety-related information is conveyed. This will elucidate how anxiety-related information is conveyed from the hippocampus to the prefrontal cortex and beyond. In this project we will use a multi-dimensional approach combining behavioural paradigms and optogenetic manipulations with electzrophysiological recording and labelling of neurons in the ventral hippocampus and prefrontal cortex. This approach will allow us to define temporal dynamics in the neuronal circuits of the ventral CA1 hippocampus and prefrontal cortex underlying the initiation, maintenance and easing of anxiogenic experiences.

Anxiety is an emotional experience that prevails in anticipation of potential threats. Thus, anxiety serves as an important alert signal to avoid and recognize potential dangers, but unbalanced anxiety levels have a major impact on the quality of life. Anxiety is thought to be reflected in neuronal circuits involving several brain areas including the hippocampus, prefrontal cortex and amygdala. We have identified neuronal correlates of anxiety in the firing patterns of neurons in the ventral CA1 hippocampus. Previously, we have identified neurons which increase their activity at places which are associated with increased levels of anxiety like exposed and unsecured, elevated platforms. In the present project, we determined how these activity patterns of hippocampal neurons evolve from the first encounter of an anxiogenic situation to the habituation and familiarization of such an experience. For this we recorded the activity of neurons in the ventral CA1 hippocampus during the free decision to explore an anxiogenic location as well as when a familiar and previously safe location was suddenly turned into a potentially dangerous environment. We successfully test the hypothesis that firing patterns in the hippocampus reflect not only the first encounter of an anxious situation but these firing patterns also subside together with the habituation and familiarization of the potentially dangerous environment. Furthermore, we developed a novel behavioural paradigm that allowed us to investigate in a quantitative manner how anxiety-related behaviour and risk taking is reflected in the activity of neurons of the ventral hippocampus. We showed how an important group of neurons, called GABAergic interneurons, set the tone for more risky or more conservative behaviour when confronted with an anxiogenic situation. We showed that these neurons exhibit different neuronal activity patterns in individuals with higher anxiety. We elucidated how anxiety-related information is processed in the hippocampus. In this project, we used a multi-dimensional approach combining behavioural paradigms with electrophysiological recording and identification of neurons in the ventral hippocampus. This approach will allowed us to define temporal dynamics in the neuronal circuits of the ventral CA1 hippocampus underlying the initiation, maintenance and easing of anxiogenic experiences.