5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress.
Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced in single stress exposed animals. This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany.
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Gruber
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
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Gilling
Sagol Department of Neurobiology and Department of Psychology, University of Haifa, Mount Carmel, 31905, Israel; Department of Genetics and Molecular Neurobiology, Institute of Biology, and Center for Behavioral Brain Sciences, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
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Albrecht
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
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Bartsch
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany.
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Çalışkan
Sagol Department of Neurobiology and Department of Psychology, University of Haifa, Mount Carmel, 31905, Israel.
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Richter-Levin
Department of Genetics and Molecular Neurobiology, Institute of Biology, and Center for Behavioral Brain Sciences, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
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Stork
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany.
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Heinemann
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, 14195 Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Medical School Brandenburg, 16816 Neuruppin, Germany. Electronic address: joachim.behr@charite.de.
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Behr
D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013315:Stress, Psychological / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid
5-HT receptors; GABAergic transmission; dentate gyrus; synaptic plasticity; two-hit stress model