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Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons
e448
Abstracts / Neuroscience Research 68S (2010) e447–e456
terol of membrane lipid rafts promotes neuronal apoptosis by increasing Kv2.1 ␣-subunit expression, which modulated by PKA pathways. doi:10.1016/j.neures.2010.07.1983
P1-a18 Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons Ju-Yun Weng , Yen-Chu Lin, Cheng-Chang Lien Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Acid-sensing ion channels (ASICs), a member of the degenerin/epithelial Na+ channel superfamily, are widely expressed in the mammalian central nervous system. Accumulating evidence suggests that ASIC current density is higher in GABAergic interneurons than that in glutamatergic pyramidal neurons (PNs) in the hippocampus. Such differential expression of ASICs in cortical networks is thought to be a key element for seizure termination. However, GABAergic interneurons are highly diverse; it is unclear whether the functional expression of ASICs differs in distinct GABAergic interneuron subtypes. Moreover, the subunit composition of ASICs in individual GABAergic interneurons remains unknown. By combining patch-clamp recording and single-cell RT-PCR analysis, we correlated ASIC currents with their gene expression in acute rat hippocampal slices. The results yielded several surprising findings. First, ASIC current density of oriens lacunosum-moleculare (O-LM) cells in the CA1 region, a classical type of dendrite-targeting interneuron, is six times greater than that of fast-spiking basket cells (BCs) in the dentate gyrus, a major class of soma-targeting interneuron. Second, the recovery of ASICs from desensitization is slowest in BCs, intermediate in PNs, and fastest in O-LM cells. Third, the tarantula venom Psalmotoxin 1, the specific blocker for ASIC1a homomers, inhibits ASIC currents in BCs but not in O-LM cells. Finally, single-cell RT-PCR analysis reveals co-expression of ASIC1a and ASIC2 subunit transcripts in O-LM cells, whereas only ASIC1a subunit transcript is detected in most BCs. Thus, differential expression of ASICs in inhibitory microcircuits likely contributes to the distinct roles of GABAergic interneurons in normal physiology and pathophysiology. doi:10.1016/j.neures.2010.07.1984
P1-a19 Contribution of BK channel in firing pattern characteristic of ataxic Purkinje neurons Iran Goudarzi Biology, Damghan University of Basic Sciences, Damghan, Iran The cerebellum underlies the control of posture, balance and fine coordination of motor movement. Since Purkinje neurons constituents the sole output of cerebellar cortex, they play vital roles in maintaining balance and regulating movement by modulating the firing response of deep cerebellar nuclei (DCN). Purkinje neuronal function impairment would be expected to cause ataxia. BK channel alpha subunit knockout (BK(/() mice suffer from cerebral ataxia and Purkinje cell dysfunction, elevated blood pressure, progressive hearing loss. Blockade of these KCa channels results in bursting and irregular firing in Purkinje cells and their knockdown or knockout causes ataxia. Thus, we studied to using of whole cell patch clamp recording under current clamp condition, firing behavior and role BK channel in firing pattern of Purkinje cell in a rat model of ataxia. Ataxia induced by 3AP injection. Our results showed block of BK channels with iberiotoxin (IbTX), a specific blocker of BK channels, affect Na+ spike configuration in both the tonic and burst firing in ataxic PCs. These finding suggested that IbTX-sensitive BK current contribute in regulating of spike configuration in tonic and burst firing of ataxic PCs. doi:10.1016/j.neures.2010.07.1985
P1-a32 Role of noradrenaline in basolateral amygdala modulation of hippocampal-prefrontal cortical long-term potentiation Ee Peng
Lim 1,2
, Gavin S.
Dawe 1,2 ,
Therese M.
Jay 3,4
1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 2 Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore 3 INSERM, U894, Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France 4 Universite Paris Descartes, Faculte de Medecine Paris Descartes, Paris, France Noradrenaline (NA), released by the locus coeruleus (LC), has been shown to play a key role in mediating the effects of stress on memory functions. The
LC provides diffuse projections which target many forebrain nuclei. Major targets relevant to stress include the hippocampus (HPC), the prefrontal cortex (PFC), and the basolateral amygdala (BLA). The HPC–PFC pathway, on the other hand, is involved in various PFC-related cognitive functions. This study was conducted to examine the effects of infusion of noradrenergic agents into the BLA on the synaptic plasticity in the rat HPC–PFC pathway in vivo. The evoked potential was recorded in the mPFC following stimulation of the CA1/subicular region of the ventral HPC in pentobarbital-anaesthetized male Sprague–Dawley rats. Infusion cannulas were implanted at the BLA prior to hippo-mPFC recording. Following baseline recording, animals received either noradrenaline (1 g/0.2 l or 3 g/0.2 l), clonidine (1.25 g/0.2 l), idazoxan (6 g/0.2 l), or saline infusion into the BLA. Long-term potentiation (LTP) was induced 20 min later. Two series of high frequency stimulation applied to the HPC induced a stable LTP in the saline-infused group (n = 9; 144.3 ± 4.2%). Noradrenaline at 1 g/0.2 l resulted in an enhancement of LTP (n = 5; 169.9 ± 3.3%) while the higher dose impaired LTP (n = 5; 126.4 ± 4.7%). Stimulating alpha-2 adrenoceptors in the BLA with clonidine enhanced LTP (n = 4; 166.7 ± 5.6%) while blocking alpha-2 adrenoceptors with idazoxan impaired LTP (n = 5; 127.9 ± 7.4%). These results suggest that the BLA may modulate in vivo synaptic plasticity at HPC–PFC synapse via noradrenergic mechanisms. doi:10.1016/j.neures.2010.07.1986
P1-b04 Differential concentration dependence of methadone on activation of -opioid receptors and block of GIRK and NMDA conductance in rat locus coeruleus Aya Matsui , John T. Williams Neuroscience Graduate Program, Vollum Institute, Oregon Health & Science University, United States Methadone activates opioid receptors to increase a potassium conductance mediated by g-protein coupled inwardly rectifying potassium (GIRK) channels. In addition, methadone blocks GIRK channels and NMDA receptors. In the present study, the concentration dependence of l- and d-methadone to activate -opioid receptors (MORs) and block GIRK and NMDA channels was examined using intracellular and whole cell recording from locus coeruleus neurons in brain slices. The EC-50 measured by the amplitude of the hyperpolarization induced by l-methadone was 37 nM and 610 nM for d-methadone. The maximum hyperpolarization evoked by both enantiomers (∼30 mV) was the same as that induced by [Met]5 enkephalin (ME), but the maximum outward current measured with whole cell voltage-clamp recording was smaller than the current induced by ME. The conclusion is that both enantiomers of methadone were partial agonists. When the concentration both l- and dmethadone was increased (10–30 M), the hyperpolarization produced by activation of ␣2-adrenoceptors was decreased, suggesting that methadone partially blocked GIRK channels. In addition, both l- and d-methadone blocked the NMDA receptor dependent current. The block of NMDA dependent current was voltage dependent suggesting that methadone acted as a channel blocker. The results indicate that methadone activates MORs at low concentrations in a stereospecific manner. GIRK and NMDA receptor channel block was not stereospecific and required at substantially higher concentrations. The separation in the concentration range suggests that the activation of MORs rather than the channel blocking properties mediate both the therapeutic and toxic actions of methadone. doi:10.1016/j.neures.2010.07.1987
P1-b08 Intracellular mechanisms underlying the inhibitory effect of alpha-2A-adrenoceptor stimulation on excitatory synaptic transmission in the rat medial prefrontal cortex Feng Yi Institute of Neurobiology, Fudan University, China Stimulation of alpha-2A-adrenoceptors (ARs) in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. Alpha-2-adrenergic agonist guanfacine has been used experimentally and clinically for treatment of psychiatric disorders such as attentiondeficit/hyperactivity disorder (ADHD). A previous study in our laboratory showed that stimulation of alpha-2A-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex (mPFC) of rat. However, the underlying mechanism is still unclear. In the present study, we recorded evoked excitatory postsynaptic current (eEPSC) in the mPFC of rats, using
Abstracts / Neuroscience Research 68S (2010) e447–e456
terol of membrane lipid rafts promotes neuronal apoptosis by increasing Kv2.1 ␣-subunit expression, which modulated by PKA pathways. doi:10.1016/j.neures.2010.07.1983
P1-a18 Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons Ju-Yun Weng , Yen-Chu Lin, Cheng-Chang Lien Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei, Taiwan Acid-sensing ion channels (ASICs), a member of the degenerin/epithelial Na+ channel superfamily, are widely expressed in the mammalian central nervous system. Accumulating evidence suggests that ASIC current density is higher in GABAergic interneurons than that in glutamatergic pyramidal neurons (PNs) in the hippocampus. Such differential expression of ASICs in cortical networks is thought to be a key element for seizure termination. However, GABAergic interneurons are highly diverse; it is unclear whether the functional expression of ASICs differs in distinct GABAergic interneuron subtypes. Moreover, the subunit composition of ASICs in individual GABAergic interneurons remains unknown. By combining patch-clamp recording and single-cell RT-PCR analysis, we correlated ASIC currents with their gene expression in acute rat hippocampal slices. The results yielded several surprising findings. First, ASIC current density of oriens lacunosum-moleculare (O-LM) cells in the CA1 region, a classical type of dendrite-targeting interneuron, is six times greater than that of fast-spiking basket cells (BCs) in the dentate gyrus, a major class of soma-targeting interneuron. Second, the recovery of ASICs from desensitization is slowest in BCs, intermediate in PNs, and fastest in O-LM cells. Third, the tarantula venom Psalmotoxin 1, the specific blocker for ASIC1a homomers, inhibits ASIC currents in BCs but not in O-LM cells. Finally, single-cell RT-PCR analysis reveals co-expression of ASIC1a and ASIC2 subunit transcripts in O-LM cells, whereas only ASIC1a subunit transcript is detected in most BCs. Thus, differential expression of ASICs in inhibitory microcircuits likely contributes to the distinct roles of GABAergic interneurons in normal physiology and pathophysiology. doi:10.1016/j.neures.2010.07.1984
P1-a19 Contribution of BK channel in firing pattern characteristic of ataxic Purkinje neurons Iran Goudarzi Biology, Damghan University of Basic Sciences, Damghan, Iran The cerebellum underlies the control of posture, balance and fine coordination of motor movement. Since Purkinje neurons constituents the sole output of cerebellar cortex, they play vital roles in maintaining balance and regulating movement by modulating the firing response of deep cerebellar nuclei (DCN). Purkinje neuronal function impairment would be expected to cause ataxia. BK channel alpha subunit knockout (BK(/() mice suffer from cerebral ataxia and Purkinje cell dysfunction, elevated blood pressure, progressive hearing loss. Blockade of these KCa channels results in bursting and irregular firing in Purkinje cells and their knockdown or knockout causes ataxia. Thus, we studied to using of whole cell patch clamp recording under current clamp condition, firing behavior and role BK channel in firing pattern of Purkinje cell in a rat model of ataxia. Ataxia induced by 3AP injection. Our results showed block of BK channels with iberiotoxin (IbTX), a specific blocker of BK channels, affect Na+ spike configuration in both the tonic and burst firing in ataxic PCs. These finding suggested that IbTX-sensitive BK current contribute in regulating of spike configuration in tonic and burst firing of ataxic PCs. doi:10.1016/j.neures.2010.07.1985
P1-a32 Role of noradrenaline in basolateral amygdala modulation of hippocampal-prefrontal cortical long-term potentiation Ee Peng
Lim 1,2
, Gavin S.
Dawe 1,2 ,
Therese M.
Jay 3,4
1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 2 Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore 3 INSERM, U894, Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France 4 Universite Paris Descartes, Faculte de Medecine Paris Descartes, Paris, France Noradrenaline (NA), released by the locus coeruleus (LC), has been shown to play a key role in mediating the effects of stress on memory functions. The
LC provides diffuse projections which target many forebrain nuclei. Major targets relevant to stress include the hippocampus (HPC), the prefrontal cortex (PFC), and the basolateral amygdala (BLA). The HPC–PFC pathway, on the other hand, is involved in various PFC-related cognitive functions. This study was conducted to examine the effects of infusion of noradrenergic agents into the BLA on the synaptic plasticity in the rat HPC–PFC pathway in vivo. The evoked potential was recorded in the mPFC following stimulation of the CA1/subicular region of the ventral HPC in pentobarbital-anaesthetized male Sprague–Dawley rats. Infusion cannulas were implanted at the BLA prior to hippo-mPFC recording. Following baseline recording, animals received either noradrenaline (1 g/0.2 l or 3 g/0.2 l), clonidine (1.25 g/0.2 l), idazoxan (6 g/0.2 l), or saline infusion into the BLA. Long-term potentiation (LTP) was induced 20 min later. Two series of high frequency stimulation applied to the HPC induced a stable LTP in the saline-infused group (n = 9; 144.3 ± 4.2%). Noradrenaline at 1 g/0.2 l resulted in an enhancement of LTP (n = 5; 169.9 ± 3.3%) while the higher dose impaired LTP (n = 5; 126.4 ± 4.7%). Stimulating alpha-2 adrenoceptors in the BLA with clonidine enhanced LTP (n = 4; 166.7 ± 5.6%) while blocking alpha-2 adrenoceptors with idazoxan impaired LTP (n = 5; 127.9 ± 7.4%). These results suggest that the BLA may modulate in vivo synaptic plasticity at HPC–PFC synapse via noradrenergic mechanisms. doi:10.1016/j.neures.2010.07.1986
P1-b04 Differential concentration dependence of methadone on activation of -opioid receptors and block of GIRK and NMDA conductance in rat locus coeruleus Aya Matsui , John T. Williams Neuroscience Graduate Program, Vollum Institute, Oregon Health & Science University, United States Methadone activates opioid receptors to increase a potassium conductance mediated by g-protein coupled inwardly rectifying potassium (GIRK) channels. In addition, methadone blocks GIRK channels and NMDA receptors. In the present study, the concentration dependence of l- and d-methadone to activate -opioid receptors (MORs) and block GIRK and NMDA channels was examined using intracellular and whole cell recording from locus coeruleus neurons in brain slices. The EC-50 measured by the amplitude of the hyperpolarization induced by l-methadone was 37 nM and 610 nM for d-methadone. The maximum hyperpolarization evoked by both enantiomers (∼30 mV) was the same as that induced by [Met]5 enkephalin (ME), but the maximum outward current measured with whole cell voltage-clamp recording was smaller than the current induced by ME. The conclusion is that both enantiomers of methadone were partial agonists. When the concentration both l- and dmethadone was increased (10–30 M), the hyperpolarization produced by activation of ␣2-adrenoceptors was decreased, suggesting that methadone partially blocked GIRK channels. In addition, both l- and d-methadone blocked the NMDA receptor dependent current. The block of NMDA dependent current was voltage dependent suggesting that methadone acted as a channel blocker. The results indicate that methadone activates MORs at low concentrations in a stereospecific manner. GIRK and NMDA receptor channel block was not stereospecific and required at substantially higher concentrations. The separation in the concentration range suggests that the activation of MORs rather than the channel blocking properties mediate both the therapeutic and toxic actions of methadone. doi:10.1016/j.neures.2010.07.1987
P1-b08 Intracellular mechanisms underlying the inhibitory effect of alpha-2A-adrenoceptor stimulation on excitatory synaptic transmission in the rat medial prefrontal cortex Feng Yi Institute of Neurobiology, Fudan University, China Stimulation of alpha-2A-adrenoceptors (ARs) in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. Alpha-2-adrenergic agonist guanfacine has been used experimentally and clinically for treatment of psychiatric disorders such as attentiondeficit/hyperactivity disorder (ADHD). A previous study in our laboratory showed that stimulation of alpha-2A-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex (mPFC) of rat. However, the underlying mechanism is still unclear. In the present study, we recorded evoked excitatory postsynaptic current (eEPSC) in the mPFC of rats, using