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Hess, G.

Publications and source records attributed to Hess, G..

3 recordsLinked to original sources

Activation of 5-HT7 receptors in the mouse dentate gyrus selectively enhances GABAergic inhibition of hilar mossy cells without affecting plasticity at the perforant path synapse

BackgroundThe study examined the effects of 5-HT7 receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input. MethodsImmunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT7 receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells -- two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT7 receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input. ResultsIt was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT7 receptors. However, activation of 5-HT7 receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT7 receptor activation on perforant path plasticity either with intact or blocked GABAA receptor signaling. ConclusionThe presence of 5-HT7 receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.

neuroscience↗

The 5-HT7 receptor antagonist SB 269970 ameliorates maternal fluoxetine exposure-induced impairment of synaptic plasticity in the prefrontal cortex of the offspring female mice

BackgroundAlthough the use of a selective serotonin reuptake inhibitor fluoxetine in depression during pregnancy is considered safe, it might increase the risk of affective disorders and cognitive symptoms in progeny. In animal models, maternal exposure to fluoxetine throughout gestation and lactation negatively affects the behavior of the offspring. Little is known about the effects of maternal fluoxetine on synaptic transmission and plasticity in the offspring cerebral cortex. MethodsDuring pregnancy and lactation C57BL/6J mouse dams received fluoxetine (7.5 mg/kg/day) with drinking water. Female offspring mice received intraperitoneal injections of the selective 5-HT7 receptor antagonist SB 269970 (2.5 mg/kg) for 7 days. Whole-cell and field potential electrophysiological recordings were performed in the medial prefrontal cortex (mPFC) ex vivo brain slices. ResultsPerinatal exposure to fluoxetine resulted in decreased field potentials and impaired long-term potentiation (LTP) in layer II/III of the mPFC of female young adult offspring. Neither the intrinsic excitability nor spontaneous excitatory postsynaptic currents were altered in layer II/III mPFC pyramidal neurons. In mPFC slices obtained from fluoxetine-treated mice that were administered SB 269970 both field potentials and LTP magnitude were restored and did not differ from controls. ConclusionsTreatment of fluoxetine-exposed mice with a selective 5-HT7 receptor antagonist, SB269970, normalizes synaptic transmission and restores the potential for plasticity in the mPFC of mice exposed in utero and postnatally to fluoxetine.

neuroscience↗

Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are a class of antidepressant drugs commonly prescribed to women during pregnancy and breastfeeding to treat depression. There is evidence that prenatal exposure to SSRIs may be associated with a higher risk of adverse cognitive outcomes and affective disorders in later life. In animal models, exposure to SSRIs during brain development results in behavioral alterations as well as structural abnormalities of cerebral cortical neurons. Little is known about the consequences of SSRI- induced excess of 5-HT during development on the brain serotonergic system itself. In this study, an SSRI - fluoxetine (FLX) - was administered to C57BL/6J mouse dams during pregnancy and lactation. We found that maternal FLX decreased field potentials, impaired long-term potentiation, facilitated induction of long-term depression and tended to increase the density of 5-HTergic fibers in the medial prefrontal cortex (mPFC) of female but not male adolescent offspring. These effects were accompanied by deteriorated performance in the temporal order memory task and reduced sucrose preference with no change in marble burying behavior in FLX-exposed female offspring. We also found that maternal FLX reduced the axodendritic tree complexity of 5-HT dorsal raphe nucleus (DRN) neurons in female but not male offspring. Whole-cell recordings demonstrated no changes in the excitability of DRN 5-HT neurons in FLX-exposed offspring of either sex. While no effects of maternal FLX on inhibitory postsynaptic currents (sIPSCs) in DRN neurons were found, we observed a significant influence of FLX exposure on kinetic characteristics of spontaneous excitatory postsynaptic currents (sEPSCs) in DRN neurons. Finally, we report that no changes in field potentials and synaptic plasticity were evident in the mPFC of the offspring after maternal exposure during pregnancy and lactation to a new antidepressant, vortioxetine. These findings show that in contrast to the mPFC, long-term consequences of maternal FLX exposure on the structure and function of DRN 5-HT neurons are mild and suggest a sex-dependent, distinct sensitivity of cortical and brainstem neurons to FLX exposure in early life. Regarding side effects on brain development, vortioxetine might be a safer alternative to FLX.

neuroscience↗