Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD) rats. In the present study, we ...investigated the role of metabotropic glutamate receptors (mGluRs), γ-Aminobutyric acid (GABA) B receptors (GABAB-Rs) and N-methyl-D-aspartic acid receptors (NMDARs) in the LTD of the population excitatory postsynaptic potential (pEPSP). The requirement of Ca2+ from L- and T- type voltage-gated calcium channels (VGCCs) and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca2+ from intracellular stores and GABAB-Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABAB-R antagonist, partially suppressed LTD in normally sleeping (NS) rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABAB-R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABAB-Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABAB-R1 and mGlu1αR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1αR/GABAB-R1 and mGlu1αR/GABAB-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABAB-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD) rats. In the present study, we ...investigated the role of metabotropic glutamate receptors (mGluRs), γ-aminobutyric acid (GABA) B receptors (GABA(B)-Rs) and N-methyl-D-aspartic acid receptors (NMDARs) in the LTD of the population excitatory postsynaptic potential (pEPSP). The requirement of Ca(2+) from L- and T-type voltage-gated calcium channels (VGCCs) and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca(2+) from intracellular stores and GABA(B)-Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABA(B)-R antagonist, partially suppressed LTD in normally sleeping (NS) rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABA(B)-R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABA(B)-Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABA(B)-R1 and mGlu1αR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1αR/GABA(B)-R1 and mGlu1αR/GABA(B)-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABA(B)-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Insufficient sleep has been correlated to many physiological and psychoneurological disorders. Over the years, our understanding of the state of sleep has transcended from an inactive period of rest ...to a more active state involving important cellular and molecular processes. In addition, during sleep, electrophysiological changes also occur in pathways in specific regions of the mammalian central nervous system (CNS). Activity mediated synaptic plasticity in the CNS can lead to long-term and sometimes permanent strengthening and/or weakening synaptic strength affecting neuronal network behaviour. Memory consolidation and learning that take place during sleep cycles, can be affected by changes in synaptic plasticity during sleep disturbances. G-protein coupled receptors (GPCRs), with their versatile structural and functional attributes, can regulate synaptic plasticity in CNS and hence, may be potentially affected in sleep deprived conditions. In this review, we aim to discuss important functional changes that can take place in the CNS during sleep and sleep deprivation and how changes in GPCRs can lead to potential problems with therapeutics with pharmacological interventions.
Spinal nociceptive neurons are well known to undergo a process of long-term potentiation (LTP) following conditioning by high-frequency sciatic nerve stimulation (HFS) at intensities recruiting ...C-fibers. However, little if any information exists as to whether such HFS conditioning that produces spinal LTP affects sensory transmission at supraspinal levels. The present study explored this possibility. Conventional extracellular recording methods were used to examine the consequences of HFS versus sham HFS conditioning on individual wide-dynamic range thalamic neurons located in the ventro-postero-lateral (VPL) nucleus in isoflurane-anesthetized rats. Following HFS, the ongoing firing rate and stimulus-evoked (brush, pinch, sciatic nerve) responses were markedly enhanced as were responses to juxtacellular, microiontophoretic applications of glutamate. These HFS-induced enhancements lasted throughout the recording period. Sham stimuli had no effect on VPL neuron excitability. Cortical electroencephalographic (EEG) wave activities were also measured around HFS in conjunction with VPL neuron recordings. The cortical EEG pattern under baseline conditions consisted of recurring short duration bursts of high-amplitude slow waves followed by longer periods of flat EEG. Following HFS, the EEG shifted to a continuous large-amplitude, slow-wave pattern within the 0.5-8.0 Hz bandwidth lasting throughout the recording period. Sham HFS did not alter EEG activity. Sciatic nerve conditioning at A-δ fiber strength, known to reverse spinal LTP, did not alter enhanced neuronal excitability or the EEG slow-wave pattern induced by HFS. These data support the concept that HFS conditioning of the sciatic nerve, which leads to spinal LTP, is associated with distinct, long-lasting changes in the excitability of neurons comprising thalamocortical networks.
Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD) rats. In the present study, we ...investigated the role of metabotropic glutamate receptors (mGluRs), gamma-Aminobutyric acid (GABA) B receptors (GABA.sub.B -Rs) and N-methyl-D-aspartic acid receptors (NMDARs) in the LTD of the population excitatory postsynaptic potential (pEPSP). The requirement of Ca.sup.2+ from L- and T- type voltage-gated calcium channels (VGCCs) and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca.sup.2+ from intracellular stores and GABA.sub.B -Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABA.sub.B -R antagonist, partially suppressed LTD in normally sleeping (NS) rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABA.sub.B -R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABA.sub.B -Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABA.sub.B -R1 and mGlu1alphaR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1alphaR/GABA.sub.B -R1 and mGlu1alphaR/GABA.sub.B -R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABA.sub.B -Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the central nervous system (CNS), synapses are considered to be the loci for memories. Activity dependent strengthening or weakening of synaptic strength via long-term potentiation (LTP) or ...depression (LTD), respectively, is widely postulated to underlie memory formation. Sleep, which is universally present across most species in the animal kingdom, aids learning and formation of memories. On the contrary, sleep-deprivation (short- or long- term), disrupts memory formation and task re-performance. Exactly how this happens is unclear. In the present study, we hypothesized that sleep-deprivation affects LTD, which may in-turn be responsible for cognitive deficits observed at the behavioral level. Following a 12 h period of sleep-deprivation, LTD of the population excitatory postsynaptic potentials (pEPSPs) induced using a 20 Hz, 30s tetanus to Schaffer collaterals in the CA1 region of the hippocampus, is enhanced in sleep-deprived (SD) rats. We investigated the role of metabotropic glutamate receptors (mGluRs), γ-Aminobutyric acid (GABA)-A receptors (GABAA-Rs), GABAB-Rs and N-methyl-D-aspartic acid receptors (NMDARs) in the LTD. The requirement of Ca²⁺ through L- and T- type voltage-gated calcium channels (VGCCs) and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca²⁺ from intracellular stores and GABAB-Rs are required for LTD. Studies with mGluR antagonists suggest that while mGlu1Rs are involved in both short-term depression and LTD, mGlu5Rs participate mostly in LTD. CGP-55845, a GABAB-R antagonist, partially suppressed LTD in normally sleeping (NS) rats, while completely blocking in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABAB-Rs, suppressed the pEPSP in SD, but not NS, rats. Since both mGluRs and GABAB-Rs seem to be involved in the LTD, especially in SD rats, changes in receptor expression pattern and/or dimerization were examined using immunohistochemical, co-localization and co-immunoprecipitation (co-IP) techniques. Sleep-deprivation induced an increase in GABAB-R1 and mGlu1αR expression in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1αR/GABAB-R1 and mGlu1αR/GABAB-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABAB-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.
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