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Prenatal stress in rats effects synaptic transmission in the dorsal raphe nucleus of their adolescent offspring

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Sowa J. G. , Hess G.

Acta Neurobiologiae Experimentalis

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2018

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tom 78

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nr Suppl.1

EN

Prenatal maternal stress (PS) can adversely affect the development of the central nervous system in offspring. The effects of PS become evident laterin life and may be in‑ volved in the pathogenesis of neurological and mental dis‑ orders. The dorsal raphe nucleus (DRN), as a major source of serotonin (5-HT) in the mammalian forebrain, plays a key role in the stress response. The DRN is also involved in the development of stress-related disorders. GABA-ergic and glutamatergic transmission in the DRN are modulated by the 5-HT7 receptor, however, little is known about the effects of PS on the activity of the DRN neuronal network. The aim of this study was to determine the effects of PS by analysing excitatory and inhibitory synaptic transmis‑ sion, and its modulation by the 5-HT7 receptor, in the DRN of rat adolescent offspring of stressed rat dams. Pregnant Sprague-Dawley rats were subjected daily to three restraint stress sessions, from the 14th day of pregnancy until birth. During each stress session, rats were placed in plastic cyl‑ inders and exposed to bright light for 45 min. Control preg‑ nant females were left undisturbed in their home cages. The effects of PS were studied in slices of the DRN prepared from adolescent male offspring of control and stressed mothers. Whole-cell recordings were carried out from pu‑ tative 5-HT neurons. Spontaneous excitatory (sEPSCs) and inhibitory (sIPSCs) postsynaptic currents were recorded to assess glutamatergic and GABA-ergic transmission, respec‑ tively. 5-CT, in the presence of WAY 100635, was applied to the ACSF to selectively activate the 5-HT7 receptor. In pre‑ natally-stressed rats an increased frequency of sEPSCs and a decreased frequency of sIPSCs were evident, compared to control animals. In slices originating from control rats, ac‑ tivation of the 5-HT7 receptor resulted in a decrease in the mean frequency of sEPSCs and an increase in the mean fre‑ quency of sIPSCs. These effects were absent from slices ob‑ tained from prenatally-stressed rats. These results suggest that prenatal maternal stress in rats causes an enhance‑ ment of glutamatergic transmission and an attenuation of GABA-ergic transmission and affects the function of the 5-HT7 receptor in the DRN of their adolescent offspring. These effects may be related to prenatal stress-induced ab‑ normalities in the functioning of the serotonergic system. Support: This study was supported by grant 2015/17/N/ NZ4/02455, National Science Centre Poland.

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Prenatal stress induces changes in excitatory and inhibitory synaptic transmission in the dorsal raphe nucleus of adolescent rats

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Sowa J. G. , Hess G.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

EN

Prenatal maternal stress (PS) adversely influences the development of the central nervous system. Its effects become evident later in life and may lead to mental and neurological disorders. The dorsal raphe nucleus (DRN) is a major source of serotonin in the mammalian brain. DRN plays a key role in regulation of the stress response and is involved in the development of stress-related psychiatric disorders. Little is known of the effect of prenatal stress on the DRN. In particular, it is not known how PS influences excitatory and inhibitory synaptic transmission and the properties of neurons in the DRN. The aim of this study was to determine the effects of prenatal stress on glutamatergic and GABAergic inputs to DRN serotonergic neurons of the rat. Pregnant Sprague-Dawley rats were subjected daily to three restraint stress sessions, from 14th day of pregnancy until the delivery. The effects of this treatment were studied in slices of the DRN prepared from adolescent male offspring of control and stressed mothers. Whole-cell recordings were carried out from putative serotonergic neurons in DRN slices. Spontaneous excitatory (sEPSCs) and inhibitory (sIPSCs) postsynaptic currents were recorded to assess glutamatergic and GABA-ergic transmission, respectively. Prenatal stress caused an increase in the frequency of sEPSCs and a decrease in the frequency of sIPSCs. Basic electrophysiological properties of serotonergic neurons in rat dorsal raphe nucleus, such as resting membrane potential, input resistance and excitability were not changed after prenatal stress. These results suggest that prenatal maternal stress causes an enhancement of glutamatergic transmission and an attenuation of GABAergic transmission in the DRN of adolescent offspring rats. These effects are likely to affect the function of the serotonergic system. FINANCIAL SUPPORT: This study was supported by grant 2015/17/N/NZ4/02455, National Science Centre Poland. Joanna Sowa is a holder of scholarship from the KNOW sponsored by Ministry of Science and Higher Education, Republic of Poland.

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5-HT7 receptor-dependent modulation of gabaergic and glutamatergic transmission in the dorsal raphe nucleus of the rat

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Tokarski K. , Kusek M. , Sowa J. G. , Hess G.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

EN

The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN are localized on the GABAergic interneurons and glutamatergic terminals which modulate the activity of 5-HT DRN projection neurons. The present study was aimed at finding how the 5‑HT7 receptor modulates the GABAergic and glutamatergic synaptic inputs to 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5‑HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist SB 269970, which induced an increase in the levels of 5-HT and its metabolite, 5 hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out from DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5‑HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of a selective 5-HT1A receptor antagonist WAY100635. Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Application of 5-CT induced a concentration-dependent increase in the frequency of sIPSCs and a decrease in sEPSCs frequency in recorded neurons. Blockade of 5‑HT7 receptors caused opposite effects. FINANCIAL SUPPORT: Supported by the grant DEC‑2013/11/B/NZ4/04743, financed by the National Science Center, Poland, and by statutory funds from the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.