Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 35

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
BACKGROUND AND AIMS: The hypothalamic paraventricular nucleus (PVN) plays a key role in the activation of the hypothalamic-pituitary-adrenal axis (HPA). In response to stress, corticotropin releasing hormone (CRH) is released from parvocellular PVN neurosecretory neurons into hypophysial portal vessels that access the anterior pituitary gland to stimulate the production of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce glucocorticoid hormones.  It is known that excitatory and inhibitory inputs that regulate the activity of parvocellular PVN neurosecretory neurons may undergo stress-related modifications. However, the influence of acute restraint stress on the function of glutamatergic and GABAergic synapses in PVN is not fully understood. METHODS: Adolescent male Wistar rats were subjected to acute restraint lasting 10 min. Animals were decapitated either immediately after the stress session or 24 hours later. Whole-cell patchclamp was used to record spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs/mEPSCs, sIPSCs/ mIPSCs) from parvocellular neuroendocrine neurons of the PVN ex vivo. RESULTS: In animals decapitated immediately after the stress session, an increase in the mean frequency of sEPSCs/mEPSCs was observed. These effects were accompanied by a decrease in the mean frequency of sIPSCs/mIPSCs. The kinetics and amplitude of the currents remained unchanged. In slices prepared 24 h after the restraint there was no change in the frequency and amplitude of all recorded currents. Also the basal electrophysiological properties and the excitability of the neurosecretory parvocellular neurons remained unchanged in all tested slices. CONCLUSIONS: Acute immobilization stress results in a transient (less than 24 h) enhancement of the glutamatergic and an attenuation of the GABAergic synaptic input to neurosecretory parvocellular neurons in the rat PVN. Support: Grant 2012/07/N/NZ4/02687.
The barrel cortex is part of rodent primary somatosensory cortex, engaged in processing tactile information from the vibrissae. This part of the cortex contains layer IV cytoarchitectonic units – barrels, each corresponds to one of the contralateral vibrissae. Short-term, classical conditioning paradigm, consisting of three daily sessions of tactile stimulation of a row of vibrissae paired with electrical shock to the tail, induces expansion of the representation of stimulated vibrissae, pronounced in layer IV of adult mice barrel cortex. This effect has been accompanied by elevation in mRNA and protein level of GAD67, selective up-regulation of GABA and GAD67 in neurons within centres of the barrels receiving inputs from stimulated vibrissae, and an increase in the number of GADimmunoreactive puncta. To investigate whether classical conditioning affects synaptic transmission in layer IV of the barrel cortex we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using ex vivo brain slices prepared from adult mice previously subjected to conditioning. We show that this associative learning paradigm results in a selective increase in the frequency of sIPSCs in layer IV excitatory neurons located within the barrel representing stimulated vibrissae, evident 24 h after the end of training. These data indicate that aversive training results in a selective and long-lasting enhancement of GABAergic transmission within the cortical representation of stimulated vibrissae.
INTRODUCTION: Experimental evidence points to the 5-HT7 receptor as a potential therapeutic target for affective and neurodevelopmental disorders. The cellular/ ionic mechanisms following the activation of the 5-HT7 receptor signaling pathway have not yet been fully characterized. Our preliminary recordings from hippocampal neurons have shown that 5-HT7 activation, in addition to increasing neural excitability, shortens action potential latency, which suggests involvement of voltage-gated potassium channels in the neural response to 5-HT7 activation. AIM(S): The aim of our study was to directly investigate modulatory effects of 5‑HT7 activation on voltage‑gated potassium channels in rat CA1 pyramidal cells, as well as to examine the functional consequences of such effects on the hippocampal circuitry. METHOD(S): We performed whole-cell voltage clamp recordings from rat CA1 pyramidal cells and tested the effects of 5‑HT7 agonists on A‑type and delayed rectifier potassium currents. To examine the influence of the 5-HT7-mediated channel modulation on synaptic transmission, we stimulated Schaffer collaterals and recorded evoked AMPA currents before and after 5-HT7 activation, as well as before and after blocking Kv4.3/Kv4.4 and/or HCN channel subunits. RESULTS: Activation of 5-HT7 receptors markedly attenuated A-type potassium currents in CA1 pyramidal cells. Furthermore, 5-HT7 activation increased AMPA postsynaptic currents evoked by stimulation of Schaffer collaterals, and this effect was partially dependent on the inhibition of A-type potassium channels. CONCLUSIONS: We found that 5-HT7 receptors can strongly influence neural activity by inhibiting A‑type potassium currents, which affects both neural excitability and response dynamics, as well as CA3 -> CA1 synaptic transmission. FINANCIAL SUPPORT: The study was supported by Ministry of Science and Higher Education (Warsaw, Poland) grant no 2016/21/B/NZ4/03618 and statutory funds from the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. M.S. and J.E.S. are beneficiaries of the KNOW PhD scholarship sponsored by the Ministry of Science and Higher Education, Poland.
Hippocampal GABAergic interneurons modulate the activity of principal glutamatergic cells. Hippocampus receives 5-HT innervation originating in raphe nuclei. In this study we aimed at establishing whether the 5-HT7 receptor-dependent modulation of hippocampal functions also involves local inhibitory circuits. We investigated the effects of 5-HT7 receptor activation on the glutamatergic input to stratum lacunosum moleculare GABAergic interneurons and on the GABAergic input to pyramidal cells of the CA1 area. The experiments were performed on hippocampal slices using whole-cell patch-clamp technique. Neurons were visualized and identified by the shape of the soma as well as by the spiking pattern. For the recording of sIPSCs neurons were voltage clamped at 0 mV and sEPSCs were recorded at -76 mV. The amplitude and the frequency of sIPSCs recorded from pyramidal neurons as well as the amplitude and the frequency of sEPSCs recorded from GABA interneurons were measured. To activate the 5-HT7 receptor, 5-CT (a nonselective 5-HT7 receptor agonist) was applied in the presence of WAY 100635 (the 5-HT1A receptor antagonist). The application of 5-CT increased the mean frequency of sIPSCs and sEPSCs while the mean amplitudes of sIPSCS and sEPSCs were not altered. In the presence of a nonselective glutamate receptor antagonist, kynurenic acid, 5-CTmediated increase in the sIPSCs frequency was still present. These data suggest that the activation of the 5-HT7 receptor results in an enhancement of the GABAergic transmission via two mechanisms. The first one is an enhancement of excitatory glutamatergic input to GABAergic interneurons and the second - an increase of the excitability of GABAergic cells and /or an increase of GABA release due the activation of 5-HT7 receptors located in the perisomatic region of GABAergic cells and/or on GABAergic terminals. Support: MNiSW grant 0259/B/P01/2010/38.
The hypothalamic paraventricular nucleus (PVN) plays a key role in the activation of the hypothalamic-pituitary-adrenal axis (HPA) in response to stressors. Wistar rats were subjected to restraint lasting 10 min and repeated twice daily for 3 days. Brain slices were prepared 24 h after the last restraint session and studied ex vivo. Whole-cell patch-clamp method was used to record spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) from presumed parvocellular neurosecretory neurons in slices containing a part of the PVN. Repeated restraint stress resulted in an increase in the mean frequency of sEPSCs and in a decrease in the rise time and the decay time constant of sEPSCs. There were no changes in the mean amplitude of sEPSC. All measured parameters of sIPSCs remained unaltered. The relationship between the injected current and the spiking rate of parvocellular neurons was reduced. These data indicate that restraint stress, repeated for 3 days, selectively enhances the excitatory inputs to parvocellular neurons of the PVN, most likely via a combination of pre- and postsynaptic mechanisms. These changes are accompanied by a decrease in the intrinsic excitability of PVN neurons. Support: “DeMeTer” and statutory funds from the Institute of Pharmacology.
Using extracellular recording we studied changes in the reactivity of rat hippocampal slices to an agonist of the 5-HT7 receptor, 5-carboxamidotryptamine (5-CT; 0.025-1 µM), induced by an earlier treatment of animals with corticosterone. Spontaneous bursting activity was recorded in ex vivo slices incubated in the presence of 2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635; 2 µM), an antagonist of the 5-HT1A receptor, in the medium devoid of Mg2+ ions. Saturation binding assays were performed using [3H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), a specific antagonist of the 5-HT7 receptor. Repetitive, but not single, corticosterone administration lasting 7 and 21 days, resulted in an enhancement of the effect related to the 5-HT7 receptor activation without changes in its binding properties. In a separate set of experiments rats were treated with corticosterone for 3 weeks and additionally with imipramine, beginning on the eighth day of corticosterone administration. In the corticosterone plus imipramine group the excitatory effect of 5-CT was weaker than in the corticosterone group, indicating that corticosterone-induced functional modifications in the reactivity of the 5-HT7 receptor were reversed and further weakened by imipramine treatment. This effect was accompanied by a reduction in the density of [3H]-SB 269970 binding sites. Thus, imipramine treatment counteracts the corticosterone-induced increase in the reactivity of the hippocampal circuitry to the activation of the 5-HT7 receptor.
INTRODUCTION: Emerging evidence suggests the 5-HT7 receptor as a therapeutic target in stress-related disorders. Precise effects of the 5‑HT7‑mediated regulation of neuronal excitability remain to be elucidated. Preliminary recordings from rat CA1 piramidal neurons showed that 5-HT7 activation shortens the latency of the first spike in response to depolarization. Due to their rapid kinetics and fast recovery from inactivation, A-type potassium channels (KA) are prime candidates for mediating this effect. AIM(S): The aim of our study was to assess whether the changes in neuronal excitability and response dynamics of CA1 pyramidal cells following the activation of 5-HT7 receptors are due to inhibition of A-type K+ channels. METHOD(S): Whole-cell patch-clamp recordings were performed in current-clamp mode. Neurons were held at −65 mV and their excitability was assessed using depolarizing current pulses. To activate 5-HT7 receptors, 5‑CT (250 nM) was applied along with WAY 100635 (2 µM), a 5-HT1A antagonist. Further recordings were performed in the presence of specific blockers of A‑type and H‑type channels. RESULTS: Activation of 5-HT7 receptors increased the excitability of CA1 pyramidal cells as well as decreased the latency to 1st spike, and effect which was prevented by using a specific Kv4.3/Kv4.4 channel blocker. Blockade of HCN channels did not affect the decrease in spike latency. CONCLUSIONS: Our data show that activation of 5-HT7 influences neuronal excitability in CA1 pyramidal cells partly by inhibiting fast-inactivating A-type potassium channels. These results help further explain the physiological role of the 5-HT7 receptor, hopefully leading to better understanding of its role in nervous system physiology and pathology. FINANCIAL SUPPORT: This study was supported by the Ministry of Science and Higher Education (Warsaw, Poland) grant no 2016/21/B/NZ4/03618 and statutory founds from the Department of Physiology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. J.E.S ans M.S. are beneficiaries of the KNOW PhD scholarship sponsored by the Ministry of Science and Higher Education, Poland.
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.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.