| 1. |
- Adermark, Louise, 1974, et al.
(författare)
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Combined activation of L-type Ca2+ channels and synaptic transmission is sufficient to induce striatal long-term depression.
- 2007
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 27:25, s. 6781-7
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Tidskriftsartikel (refereegranskat)abstract
- Changes in synaptic strength at striatal synapses, such as long-term depression (LTD), may be involved in striatal-based learning and memory. Several molecular mechanisms have been implicated in striatal LTD, but it is not clear which mechanisms are crucial for LTD induction. We found that the activation of L-type calcium channels by 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methylester (FPL64176), combined with modest postsynaptic depolarization and synaptic activation, is sufficient to induce robust LTD (FPL-LTD). The L-channel activator 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2(trifluoromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (Bay K 8644) has a similar action. FPL-LTD occludes LTD induced by high-frequency stimulation (HFS-LTD) and requires elevated postsynaptic calcium and retrograde endocannabinoid signaling, properties similar to those of HFS-LTD. In contrast, FPL-LTD does not require the activation of metabotropic glutamate receptors (mGluRs), phospholipase C, or dopamine D2 receptors. FPL-LTD induction also requires afferent stimulation. These findings suggest a scenario in which L-type calcium channel activation is a crucial switch for LTD induction, and mGluRs and D2 receptors can be bypassed if this channel is activated.
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| 2. |
- Adermark, Louise, 1974, et al.
(författare)
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Electrophysiological properties and gap junction coupling of striatal astrocytes.
- 2008
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Ingår i: Neurochemistry international. - : Elsevier BV. - 0197-0186. ; 52:7, s. 1365-72
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is the biggest nucleus of the basal ganglia and receives input from almost all cortical regions, substantia nigra and the thalamus. Striatal neuronal circuitry is well characterized, but less is known about glial physiology. To this end, we evaluated astrocyte electrophysiological properties using whole-cell patch-clamp recording in dorsal striatal brain slices from P15 to P21 rat. The majority of cells (95%) were passive astrocytes that do not express any detectable voltage-gated channels. Passive astrocytes were subcategorized into three groups based on time-dependent current properties. The observed proportion of the different astrocyte subtypes did not change within the age range evaluated here, but was modulated during reduction of specific conductances and gap junction coupling. Striatal astrocytes were extensively interconnected and closure of gap junctions with octanol (1mM), carbenoxolone (100 microM) or increased intracellular calcium (2mM), significantly altered intrinsic properties. When simultaneously blocking potassium channels and gap junction coupling almost no passive conductance was detected, implying that the major currents in striatal astrocytes derive from potassium and gap junction conductance. Uncoupling of the syncytium reduced currents activated in response to a hyperpolarizing pulse, suggesting that changes in gap junction coupling alters astrocyte electrophysiological responses. Our findings indicate that the prevalent gap junction coupling is vital for astrocyte function in the striatum, and that whole-cell recordings will be distorted by currents activated in neighboring cells.
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| 3. |
- Adermark, Louise, 1974, et al.
(författare)
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Endocannabinoid-dependent plasticity at GABAergic and glutamatergic synapses in the striatum is regulated by synaptic activity.
- 2009
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Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 29:1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- Long-term depression (LTD) at striatal synapses is mediated by postsynaptic endocannabinoid (eCB) release and presynaptic cannabinoid 1 receptor (CB(1)R) activation. Previous studies have indicated that eCB mobilization at excitatory synapses might be regulated by afferent activation. To further address the role of neuronal activity in synaptic plasticity we examined changes in synaptic strength induced by the L-type calcium channel activator 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methyl ester (FPL 64176, FPL) at glutamatergic and gamma-aminobutyric acid (GABA)ergic synapses in the striatum. We found that the basic mechanisms for FPL-mediated eCB signaling are the same at glutamatergic and GABAergic synapses. FPL-induced LTD (FPL-LTD) was blocked in slices treated with the CB(1)R antagonist AM251 (2 microm), but established depression was not reversed by AM251. FPL-LTD was temperature dependent, blocked by protein translation inhibitors and prevented by intracellular loading of the anandamide transporter inhibitor VDM11 (10 microm) at both glutamatergic and GABAergic synapses. FPL-LTD at glutamatergic synapses required paired-pulse afferent stimulation, while FPL-LTD at GABAergic synapses could be induced even in the absence of explicit afferent activation. By evaluating tetrodotoxin-insensitive spontaneous inhibitory postsynaptic currents we found that neuronal firing is vital for eCB release and LTD induction at GABAergic synapses, but not for short-term depression induced by CB(1)R agonist. The data presented here suggest that the level of neuronal firing regulates eCB signaling by modulating release from the postsynaptic cell, as well as interacting with presynaptic mechanisms to induce LTD at both glutamatergic and GABAergic synapses in the striatum.
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| 4. |
- Adermark, Louise, 1974, et al.
(författare)
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Ethanol effects on electrophysiological properties of astrocytes in striatal brain slices.
- 2006
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 51:7-8, s. 1099-108
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Tidskriftsartikel (refereegranskat)abstract
- Ethanol (EtOH) is known to alter neuronal physiology, but much less is known about the actions of this drug on glial function. To this end, we examined acute effects of ethanol on resting and voltage-activated membrane currents in striatal astrocytes using rat brain slices. Ten minutes exposure to 50mM EtOH reduced slope conductance by 20%, increased input resistance by 25% and decreased capacitance by 38% but did not affect resting membrane potential. Current generated by a hyperpolarizing pulse was inhibited in a concentration dependent manner in passive astrocytes, while no significant EtOH effect was observed in complex astrocytes or neurons. The EtOH effect was blocked when intracellular KCl was replaced with CsCl, but not during chelation of intracellular calcium with BAPTA. During blockage of gap junction coupling with high intracellular CaCl(2) or extracellular carbenoxolone the EtOH effect persisted but was reduced. Interestingly, EtOH effects were largely irreversible when gap junctions were open, but were fully reversible when gap junctions were closed. Ethanol also reduced the spread to other cells of Lucifer Yellow dye from individual glia filled via the patch pipette. These data suggest that EtOH inhibits a calcium-insensitive potassium channel, most likely a passive potassium channel, but also affects gap junction coupling in a way that is sustained after ethanol withdrawal. Astrocytes play a critical role in brain potassium homeostasis, and therefore EtOH effects on astrocytic function could influence neuronal activity.
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| 5. |
- Adermark, Louise, 1974, et al.
(författare)
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Frequency-dependent inversion of net striatal output by endocannabinoid-dependent plasticity at different synaptic inputs.
- 2009
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 29:5, s. 1375-80
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how striatal neurons integrate glutamatergic and GABAergic inputs is essential for understanding the control of movement and the formation of striatal-based memories. Here we show that GABAergic synapses on striatal medium spiny neurons (MSNs) are more sensitive than glutamatergic synapses on the same cells to endocannabinoid (eCB) signaling, and that protocols that induce short-lasting cannabinoid 1 receptor (CB(1)R)-dependent depression at glutamatergic synapses are sufficient to induce long-term depression (LTD) at GABAergic synapses. We also show that the frequency and duration of glutamatergic input are strong determinants of the net effect of eCB signaling, and key factors in determining if LTD has a net disinhibitory or inhibitory action in striatum. Plastic changes in net output from striatal MSNs are thus a complex function of disinhibitory and inhibitory LTD combined with other forms of synaptic plasticity such as long-term potentiation at excitatory synapses.
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| 6. |
- Adermark, Louise, 1974, et al.
(författare)
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Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step.
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 104:51, s. 20564-9
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Tidskriftsartikel (refereegranskat)abstract
- Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic strength by retrograde transsynaptic signaling. Previous studies have suggested that an eCB mobilization or release step in the postsynaptic neuron is involved in this retrograde signaling. However, it is not known whether this release process occurs automatically upon eCB synthesis or whether it is regulated by other synaptic factors. To address this issue, we loaded postsynaptic striatal medium spiny neurons (MSNs) with the eCBs anandamide (AEA) or 2-arachidonoylglycerol and determined the conditions necessary for presynaptic inhibition. We found that presynaptic depression of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent activation that varied between the different synaptic types. Synaptic depression at excitatory synapses was temperature-dependent and blocked by the eCB membrane transport blockers, VDM11 and UCM707, but did not require activation of metabotropic glutamate receptors, l-calcium channels, nitric oxide, voltage-activated Na(+) channels, or intracellular calcium. Application of the CB(1)R antagonist, AM251, after depression was established, reversed the decrease in EPSC, but not in IPSC, amplitude. Direct activation of the CB(1) receptor by WIN 55,212-2 initiated synaptic depression that was independent of afferent stimulation. These findings indicate that retrograde eCB signaling requires a postsynaptic release step involving a transporter or carrier that is activated by afferent stimulation/synaptic activation.
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| 7. |
- Blackwell, Kim T., et al.
(författare)
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Molecular mechanisms underlying striatal synaptic plasticity : relevance chronic alcohol consumption and seeking
- 2019
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 49:6, s. 768-783
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Tidskriftsartikel (refereegranskat)abstract
- The striatum, the input structure of the basal ganglia, is a major site learning and memory for goal-directed actions and habit formation. iny projection neurons of the striatum integrate cortical, thalamic, d nigral inputs to learn associations, with cortico-striatal synaptic asticity as a learning mechanism. Signaling molecules implicated in naptic plasticity are altered in alcohol withdrawal, which may ntribute to overly strong learning and increased alcohol seeking and nsumption. To understand how interactions among signaling molecules oduce synaptic plasticity, we implemented a mechanistic model of gnaling pathways activated by dopamine D1 receptors, acetylcholine ceptors, and glutamate. We use our novel, computationally efficient mulator, NeuroRD, to simulate stochastic interactions both within and tween dendritic spines. Dopamine release during theta burst and 20-Hz imulation was extrapolated from fast-scan cyclic voltammetry data llected in mouse striatal slices. Our results show that the combined tivity of several key plasticity molecules correctly predicts the currence of either LTP, LTD, or no plasticity for numerous perimental protocols. To investigate spatial interactions, we imulate two spines, either adjacent or separated on a 20-mu m ndritic segment. Our results show that molecules underlying LTP hibit spatial specificity, whereas 2-arachidonoylglycerol exhibits a atially diffuse elevation. We also implement changes in NMDA ceptors, adenylyl cyclase, and G protein signaling that have been asured following chronic alcohol treatment. Simulations under these nditions suggest that the molecular changes can predict changes in naptic plasticity, thereby accounting for some aspects of alcohol use sorder.
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| 8. |
- Yin, Henry H, et al.
(författare)
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Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum.
- 2007
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Ingår i: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 25:11, s. 3226-32
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is important to understand the effects of this drug on striatal function. In this study we examined the effects of ethanol on long-term synaptic plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a central role in the acquisition and selection of goal-directed actions. Ethanol was found to impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent long-term potentiation (LTP) dose-dependently in the DMS, and to promote long-term depression (LTD) at the highest concentration (50 mm) used. These results suggest that ethanol, at a concentration usually associated with mild intoxication, could significantly change experience-dependent modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions.
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| 9. |
- Yin, Henry H, et al.
(författare)
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Neurotensin reduces glutamatergic transmission in the dorsolateral striatum via retrograde endocannabinoid signaling.
- 2008
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 54:1, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- Neurotensin is a peptide that has been suggested to mimic the actions of antipsychotics, but little is known about how it affects synaptic transmission in the striatum, the major input nucleus of the basal ganglia. In this study we measured the effects of neurotensin on EPSCs from medium spiny projection neurons in the sensorimotor striatum, a region implicated in habit formation and control of motor sequences. We found that bath-applied neurotensin reduced glutamate release from presynaptic terminals, and that this effect required retrograde endocannabinoid signaling, as it was prevented by the CB1 cannabinoid receptor antagonist AM251. Neurotensin-mediated inhibition of striatal EPSCs was also blocked by antagonists of D2-like dopamine receptors and group I metabotropic glutamate receptors, as well as by intracellular calcium chelation and phospholipase C inhibition. These results suggest that neurotensin can indirectly engage an endocannabinoid-mediated negative feedback signal to control glutamatergic input to the basal ganglia.
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