Projects

Serotonergic neurotransmission modulates plastic changes involved in learning and memory formation as well as emotional behavior and hence, imbalances in serotonergic neurotransmission are thought to be involved in the etiology of many mental disorders. Among other findings, reduced activity of serotonergic neurotransmission has been postulated to play a role in the pathogenesis of depression. Antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs) results in elevated extracellular serotonin levels which in turn induce long-term neuroadaptive processes mediated by neurotrophic and neuroprotective factors many of which are glia-derived. In the current models of antidepressant action many different endpoints of SSRI-induced elevated extracellular serotonin are discussed. Among others this involves neurogenesis, gliogenesis, synaptogenesis and axonal sprouting due to the release of neurogenic, neurotrophic and neuroprotective factors many of which are glia-derived. Some of these factors such as cholesterol, thrombospondins, estradiol, and S100B also play an important role in proper neuronal function. In the recent years also glia-derived polyunsaturated omega-3 fatty acids have been reported to play an important role in mental disorders and learning mechanisms (McNamara and Carlson, 2006; He et al., 2009; Kan et al., 2007). Most knowledge on the effects of the above mentioned substances on brain plasticity has been obtained so far in animal experiments or in primary neuronal cultures with a focus on glutamatergic neurotransmission. Our hypothesis is that neurotrophins and glia-derived factors released upon SSRI treatment not only impact on glutamatergic and GABAergic neurons but also on serotonergic neurotransmission. We will examine the effect of these substances on the morphology and function of serotonergic neurons in vitro and translate the respective to the serotonergic system and its impact on brain plasticity in vivo.