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Project 14: Expectation maintenance vs. change in animal models: serotonin – orchestrating associative learning and neuronal plasticity processes

Prof. Dr. Markus Wöhr (Behavioral Neuroscience)

PhD Student: Parnian Saberi

We plan to investigate neurobiological mechanisms underlying psychological processes involved in expectation maintenance vs. change after expectation violations by means of a translational approach in rats. The serotonergic (5-HT) system has been repeatedly implicated in cognitive flexibility, with alterations in its components resulting in exaggerated persistence of expectations, as reflected by impairments in extinction and/or reversal learning. Brain 5-HT synthesis depends on the rate limiting enzyme tryptophan hydroxylase 2 (gene: TPH2), with extracellular levels of 5-HT being primarily regulated by reuptake through the 5-HT transporter (SERT; gene: SLC6A4). SERT is the target of the selective serotonin reuptake inhibitors (SSRIs), a widely used class of antidepressants. SSRIs increase the extracellular levels of serotonin by limiting its reuptake into the presynaptic cell through blocking the serotonin transporter. However, as antidepressant effects are only detected after prolonged treatment for several weeks, it is unlikely that the acute increase in extracellular serotonin is responsible for their mood enhancing properties. The delayed onset rather indicates that relatively slow changes in neuronal plasticity processes are crucial candidates to ensure antidepressant effects, most notably adult hippocampal neurogenesis. In fact, a recent series of studies found that the antidepressant effects of SSRIs depend on the treatment context and that adult hippocampal neurogenesis driving these effects is strongly regulated by environmental factors, such as environmental enrichment and juvenile social isolation. Here, we therefore plan to study the interplay between serotonin and environmental factors in expectation maintenance vs. change after expectation violations through an integration of genetic, pharmacological, and/ or neurobiological approaches with behavioral studies in rats.

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