Serotonin 5-HT1A Receptor-Mediated Reduction of Excitatory Synaptic Transmission in Layers II/III of the Parasubiculum

Carter, Francis; Chapman, C. Andrew

doi:10.1016/j.neuroscience.2019.03.024

Cited by 4 publications

(3 citation statements)

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“…Loss of cholinergic inputs during AD may therefore contribute to excitotoxicity by enhancing glutamate release. Similarly, serotonin hyperpolarizes neurons and suppresses excitatory synaptic transmission in the EC (Carter and Chapman, 2019;Ma et al, 2007), and loss of serotonergic inputs may also facilitate synaptic transmission during the progression of AD.…”

Section: Loss Of Modulatory Transmitters In the Ecmentioning

confidence: 99%

Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease

2021

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The entorhinal cortex (EC) is a vital component of the medial temporal lobe, and its contributions to cognitive processes and memory formation are supported through its extensive interconnections with the hippocampal formation. During the pathogenesis of Alzheimer's disease (AD), many of the earliest degenerative changes are seen within the EC. Neurodegeneration in the EC and hippocampus during AD has been clearly linked to impairments in memory and cognitive function, and a growing body of evidence indicates that molecular and functional neurodegeneration within the EC may play a primary role in cognitive decline in the early phases of AD. Defining the mechanisms underlying molecular neurodegeneration in the EC is crucial to determining its contributions to the pathogenesis of AD. Surprisingly few studies have focused on understanding the mechanisms of molecular neurodegeneration and selective vulnerability within the EC. However, there have been advancements indicating that early dysregulation of cellular and molecular signaling pathways in the EC involve neurodegenerative cascades including oxidative stress, neuroinflammation, glia activation, stress kinases activation, and neuronal loss. Dysfunction within the EC can impact the function of the hippocampus, which relies on entorhinal inputs, and further degeneration within the hippocampus can compound this effect, leading to severe cognitive disruption. This review assesses the molecular and cellular mechanisms underlying early degeneration in the EC during AD. These mechanisms may underlie the selective vulnerability of neuronal subpopulations in this brain region to the disease development and contribute both directly and indirectly to cognitive loss.This paper has an associated Future Leader to Watch interview with the first author of the article.

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Section: Loss Of Modulatory Transmitters In the Ecmentioning

confidence: 99%

Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease

2021

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“…Paired-pulse tests were used to determine whether changes in fEPSP amplitude induced by E2 or G1 could be due to either enhanced presynaptic transmitter release or enhanced postsynaptic responsiveness (Carter & Chapman, 2019;Kumar et al, 2015). Ten pairs of pulses, with an interpulse interval of 20 ms, were delivered once every 30 s at the beginning of the baseline period, to reduce possible effects at the onset of drug application, at the end of the drug-application period, and at the end of the washout period.…”

Section: Pharmacologymentioning

confidence: 99%

“…The application of E2 ( 10 (Carter & Chapman, 2019;Kumar et al, 2015). In comparison with paired-pulse responses recorded at the start of the baseline period, after the 20-min application of E2 there was an increase in the amplitude of the response to the first pulse (109.7 ± 2.6% of baseline; F 2,36 = 5.53, p < .01), but no significant change in paired-pulse ratios, which were 0.588 ± 0.053 during baseline and 0.559 ± 0.048 in E2 (n = 19, F 2,36 = 1.94, p = .16) (Figure 1c).…”

Section: E2 Progesterone and Allopregnanolonementioning

confidence: 99%

G protein‐coupled estrogen receptor‐1 enhances excitatory synaptic responses in the entorhinal cortex

et al. 2021

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Activation of estrogen receptors is thought to modulate cognitive function in the hippocampus, prefrontal cortex, and striatum by affecting both excitatory and inhibitory synaptic transmission. The entorhinal cortex is a major source of cortical sensory and associational input to the hippocampus, but it is unclear whether either estrogens or progestogens may modulate cognitive function through effects on synaptic transmission in the entorhinal cortex. This study assessed the effects of the brief application of either 17-β estradiol (E2) or progesterone on excitatory glutamatergic synaptic transmission in the female rat entorhinal cortex in vitro. Rats were ovariectomized on postnatal day (PD) 63 and also received subdermal E2 implants to maintain constant low levels of circulating E2 on par with estrus. Electrophysiological recordings from brain slices were obtained between PD70 and PD86, and field excitatory postsynaptic potentials (fEPSPs) reflecting the activation of the superficial layers of the entorhinal cortex were evoked by the stimulation of layer I afferents.The application of E2 (10 nM) for 20 min resulted in a small increase in the amplitude of fEPSPs that reversed during the 30-min washout period. The application of the ERα agonist propylpyrazoletriol (PPT) (100 nM) or the β agonist DPN (1 μM) did not significantly affect synaptic responses. However, the application of the G proteincoupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible increase in fEPSP amplitude similar to that induced by E2. Furthermore, the potentiation of responses induced by G1 was blocked by the GPER1 antagonist G15 (1 μM).

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Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors

et al. 2019

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Serotonin modulates cognitive processes and is related to various psychiatric disorders, including major depression. Administration of citalopram reduces the amplitude of auditory evoked potentials in depressed people and animal models, suggesting that 5-HT has an inhibitory role. Here, we characterize the modulation of excitatory post-synaptic currents by application of either 5-HT or agonists of 5-HT1A and 5-HT2 receptors, or by endogenous 5-HT evoked by citalopram on pyramidal neurons from layer II/III of rat auditory cortex. We found that application of 5-HT concentration-dependently reduces excitatory post-synaptic currents amplitude without changing the paired-pulse ratio, suggesting a post-synaptic modulation. We observed that selective agonists of 5-HT1A and 5-HT2 receptors [8-OH-DPAT (10 µM) and DOI (10 µM), respectively] mimic the effect of 5-HT on the excitatory post-synaptic currents. Effect of 5-HT was entirely blocked by co-application of the antagonists NAN-190 (1 µM) and ritanserin (200 nM). Similarly, citalopram application (1 μM) reduced the amplitude of the evoked excitatory post-synaptic currents. Reduction in the magnitude of the excitatory post-synaptic currents by endogenous 5-HT was interpolated in the dose-response curve elicited by exogenous 5-HT, yielding that citalopram raised the extracellular 5-HT concentration to 823 nM. Effect of citalopram was blocked by the previous application of NAN-190 but not ritanserin, indicating that citalopram reduces glutamatergic synaptic transmission via 5-HT1A receptors in layer II/III of the auditory cortex. These results suggest that the local activity of 5-HT contributes to decrease in the basal excitability of the auditory cortex for enhancing the detection of external relevant acoustic signals.

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Serotonin 5-HT1A Receptor-Mediated Reduction of Excitatory Synaptic Transmission in Layers II/III of the Parasubiculum

Cited by 4 publications

References 55 publications

Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease

Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease

G protein‐coupled estrogen receptor‐1 enhances excitatory synaptic responses in the entorhinal cortex

Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors

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