NEUROGPLACECELLADS

Role of adult-generated neurons in hippocampal network activity for stress integration and antidepressant effects

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Stress-related disorders, including major depression, represent the most leading cause of health problem worldwide and a large part of depressive patients remain insensitive to treatments. Hence, the uncovering of the relevant processes involved in these disorders is of crucial importance. Recent works suggest that hippocampal neurogenesis is involved in the pathophysiology and the treatment of these disorders. The ability of the adult mammals, including humans, to produce new neurons is a fascinating process that has generated considerable interests, but their precise function remains poorly understood. In this project, we aim to understand how the production of new neurons can influence hippocampal network activity and underlie antidepressant effects. We hypothesize that antidepressants, by increasing neurogenesis, may strengthen stress integration by improving the coupling between contextual information and emotional state. Accordingly, we will examine whether chronic stress, antidepressant and viral-mediated inhibition of neurogenesis in animal models can alter hippocampal cell activity, behavioral performance and stress system (HPA) activation in “emotionally-relevant” environments. A putative alteration of hippocampal activity in chronic stressed animals could be responsible for disrupted behavioral responses and emotional state, as occurring in depression. Inhibition of hippocampal neurogenesis will help to determine whether antidepressants require new neurons to reverse the detrimental effects of chronic stress on hippocampal activity, facilitating suited behavioral responses and recovery. In conclusion, investigating the specific contribution of hippocampal neurogenesis in these processes will be essential for the understanding of the normal brain functioning in encoding new representations as well as for the characterization of pathological conditions associated to stress-related disorders and of the therapeutic potentialities of manipulating neurogenesis.'

Introduzione (Teaser)

Despite initial belief, adult mammals including humans can produce new neurons. A European effort investigating the precise function of these neurons shed light into the mechanisms of antidepressant effects on the brain hippocampus.

Descrizione progetto (Article)

According to the World Health Organisation, major depression and other stress-related disorders represent a heavy global socioeconomic burden of lifelong prevalence. Administration of antidepressants is not always effective, necessitating a deeper understanding into the pathogenesis of these disorders. The hippocampus is one of the brain regions that the majority of drugs have targeted for treating depression.

Hippocampal neurons can undergo rearrangements upon environmental changes or alter their signal transmission rate if given a different sensory cue. Based on this, scientists of the EU-funded NEUROGPLACECELLADS project wished to investigate the effect of antidepressant treatments on neuronal activity and information processing in the hippocampus.

In this context, scientists implanted microelectrodes into rodent brains and recorded electrophysiology data from specific hippocampal areas. Control or antidepressant-treated rats were subjected to changes in their immediate surroundings in the form of different room or wall colour.

Treatment with antidepressants significantly affected the behavioural pattern of rodents in the unfamiliar surroundings by altering the peak firing rates of hippocampal neurons. These observations clearly indicated that antidepressants can affect information processing and reduce interferences, suggesting an improved discriminating capacity among contextual differences. Long-term this may be translated into context-appropriate behavioural responses.

Apart from revealing the mechanism of action of antidepressant drugs, the results of the project also have significant clinical implications. They demonstrate that antidepressants can restore the hippocampal control on stress systems and constitute a valid option for treating pathological conditions associated with stress.