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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 and Prof. Dr. Rainer Schwarting (Behavioral Neuroscience)

PhD Student: Mathangi Ganesan

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 neurobiological approaches with behavioral studies in rats.

Further reading:

Braun MD, Kisko TM, Witt SH, RietscheI M, Schwarting RKW & Wöhr M (2019). Long-term environmental impact on object recognition, spatial memory, and reversal learning capabilities in Cacna1c haploinsufficient rats. Human Molecular Genetics, 28, 4113-4131.

Brenes JC,  Lackinger M, Höglinger GU, Schratt G, Schwarting RKW & Wöhr M (2016). Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. Journal of Comparative Neurology, 524, 1586-1607.

Houwing DJ, Staal L, Swart JM, Ramsteijn AS, Wöhr M, de Boer SF, Olivier JDA (2019). Subjecting dams to early life stress and perinatal fluoxetine treatment differentially alters social behavior in young and adult rat offspring. Frontiers in Neuroscience, 13, e229.

Lukas M & Wöhr M (2015). Endogenous vasopressin, innate anxiety, and the emission of pro-social 50-kHz ultrasonic vocalizations during social play behavior in juvenile rats. Psychoneuroendocrinology, 56, 35-44.

Rief W, Barsky AJ, Bingel U, Döring B, Schwarting RKW, Wöhr M & Schweiger U (2016). Rethinking psychopharmacotherapy: The role of treatment context and brain plasticity in antidepressant and antipsychotic interventions. Neuroscience and Biobehavioral Reviews, 60, 51-64.

Valluy J, Bicker S, Aksoy-Aksel A, Lackinger M, Sumer S, Fiore R, Wüst T, Seffer D, Metge F, Dietrich C, Wöhr M, Schwarting RKW & Schratt G (2015). A coding-independent function of an alternative Ube3a transcript during neuronal development. Nature Neuroscience, 18, 666-673.

Wöhr M, Orduz D, Gregory P, Moreno H, Khan U, Vörckel KJ, Wolfer DP, Welzl H, Gall D, Schiffmann S & Schwaller B (2015). Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morpho-functional abnormalities. Translational Psychiatry, 5, 525.

Wöhr M, Rippberger H, Schwarting RKW & van Gaalen M (2015). Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats. Psychopharmacology, 232, 1817-1829.

Yee N, Schwarting RKW, Fuchs E & Wöhr M (2012). Enhanced production of affective ultrasonic vocalizations during fear learning in adult male rats exposed to maternal immune activation. Journal of Psychiatric Research, 46, 1199-1205.

More information on Prof. Dr. Markus Wöhr and Prof. Dr. Rainer Schwarting

More information on our PhD Students