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Jeanclaude Lacaille - One of the best experts on this subject based on the ideXlab platform.

  • trpc1 mediates slow excitatory synaptic transmission in hippocampal oriens Alveus interneurons
    Molecular Brain, 2020
    Co-Authors: Andre Kougioumoutzakis, Joe Guillaume Pelletier, Isabel Laplante, Abdessattar Khlaifia, Jeanclaude Lacaille
    Abstract:

    Hippocampal GABAergic interneurons play key roles in regulating principal cell activity and plasticity. Interneurons located in stratum oriens/Alveus (O/A INs) receive excitatory inputs from CA1 pyramidal cells and express a Hebbian form of long-term potentiation (LTP) at their excitatory input synapses. This LTP requires the activation of metabotropic glutamate receptors 1a (mGluR1a) and Ca2+ entry via transient receptor potential (TRP) channels. However, the type of TRP channels involved in synaptic transmission at these synapses remains largely unknown. Using patch-clamp recordings, we show that slow excitatory postsynaptic currents (EPSCs) evoked in O/A INs are dependent on TRP channels but may be independent of phospholipase C. Using reverse transcription polymerase chain reaction (RT-PCR) we found that mRNA for TRPC 1, 3–7 was present in CA1 hippocampus. Using single-cell RT-PCR, we found expression of mRNA for TRPC 1, 4–7, but not TRPC3, in O/A INs. Using co-immunoprecipitation assays in HEK-293 cell expression system, we found that TRPC1 and TRPC4 interacted with mGluR1a. Co-immunoprecipitation in hippocampus showed that TRPC1 interacted with mGluR1a. Using immunofluorescence, we found that TRPC1 co-localized with mGluR1a in O/A IN dendrites, whereas TRPC4 localization appeared limited to O/A IN cell body. Down-regulation of TRPC1, but not TRPC4, expression in O/A INs using small interfering RNAs prevented slow EPSCs, suggesting that TRPC1 is an obligatory TRPC subunit for these EPSCs. Our findings uncover a functional role of TRPC1 in mGluR1a-mediated slow excitatory synaptic transmission onto O/A INs that could be involved in Hebbian LTP at these synapses.

  • mglur1 5 subtype specific calcium signalling and induction of long term potentiation in rat hippocampal oriens Alveus interneurones
    The Journal of Physiology, 2006
    Co-Authors: Lisa Topolnik, Andre Kougioumoutzakis, Mounia Azzi, Jeanclaude Lacaille
    Abstract:

    Hippocampal inhibitory interneurones demonstrate pathway- and synapse-specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long-term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two-photon calcium imaging and whole-cell recordings to determine the Ca2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluR1α and mGluR5) and their role in hebbian long-term potentiation (LTP) in oriens/Alveus (O/A) interneurones. We demonstrate that mGluR1α activation elicits dendritic Ca2+ signals resulting from Ca2+ influx via transient receptor potential (TRP) channels and Ca2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca2+ transients mediated exclusively by intracellular Ca2+ release. Using Western blot analysis and immunocytochemistry, we show mGluR1α-specific extracellular signal-regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluR1α/TRP Ca2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluR1α-specific Ca2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone-specific Ca2+ signalling, critical in regulating synaptic excitability in hippocampal networks.

  • group i metabotropic glutamate receptor actions in oriens Alveus interneurons of rat hippocampal ca1 region
    Brain Research, 2004
    Co-Authors: Christine E Gee, Jeanclaude Lacaille
    Abstract:

    Abstract Group I metabotropic glutamate receptors (mGluRs) are important for hippocampal interneuron function. We used whole-cell recording and confocal imaging to characterize group I mGluR actions in CA1 oriens/Alveus interneurons in slices. In tetrodotoxin and ionotropic glutamate receptor antagonists, the group I mGluR specific agonist DHPG increased intradendritic Ca2+ levels and depolarized interneurons, whereas the group II mGluR specific agonist DCG-IV and the group III mGluR specific agonist L -AP4 did not. DHPG-induced depolarizing and Ca2+ responses were antagonized by the group I mGluR antagonist 4CPG, but only Ca2+ responses were significantly inhibited by the mGluR1 antagonist CPCCOEt. DHPG-induced depolarizing responses were not blocked by the inositol-1,4,5-trisphosphate (IP3) receptor inhibitor heparin, the protein kinase C (PKC) antagonists GF-109203X, or the inhibitor of phospholipase C (PLC) U73122. Thus, these responses to DHPG may not be transduced by the PLC→IP3/diacylglycerol (DAG) pathway classically linked to group I mGluRs. DHPG-induced depolarizations were not blocked by intracellular GDPβS or bath-application of N-ethylmaleimide (NEM), suggesting the involvement of a G protein-independent pathway. Our findings indicate that group I mGluRs induce a depolarization of oriens/Alveus interneurons via a G protein-independent mechanism different from their classic signalling pathway. Since depolarizations are associated with intracellular Ca2+ rises, these actions may be important for their synaptic plasticity and vulnerability to excitotoxicity.

  • sensitivity of synaptic gabaa receptors to allosteric modulators in hippocampal oriens Alveus interneurons
    Synapse, 2001
    Co-Authors: Christian Patenaude, Suzanne Nurse, Jeanclaude Lacaille
    Abstract:

    GABA(A) receptors are heteropentamers that are heterogeneously distributed at different synapses in the central nervous system. Although the modulation of GABA(A) receptors received much attention in hippocampal pyramidal cells, information is scarce regarding the pharmacology of these receptors in inhibitory interneurons. We investigated the pharmacological properties of GABA(A)-mediated miniature inhibitory postsynaptic currents (mIPSCs) using whole-cell voltage clamp recordings in two morphologically identified types of hippocampal CA1 interneurons, horizontal and vertical cells of stratum oriens-Alveus. The negative modulators zinc (200 microM) and furosemide (600 microM) significantly decreased the amplitude of mIPSCs. Benzodiazepine agonists also produced significant effects: 10 microM zolpidem increased the amplitude, rise time, and decay time constant (decay tau) of mIPSCs, whereas 10 microM flunitrazepam affected similarly the amplitude and decay tau, but not the rise time. The neurosteroid allopregnanolone (10 microM) prolonged the decay tau of mIPSCs. Since these modulators act on different GABA(A) receptor subunits, this pharmacological profile suggests that GABA(A) receptors at spontaneously active inhibitory synapses onto vertical and horizontal interneurons are heterogeneous and formed by co-assembly of different combinations of subunits (alpha(1-5)beta(1-3)gamma(1-3)). Furthermore, these synaptic GABA(A) receptors appear in large part pharmacologically similar to those of pyramidal cells.

  • synaptically activated calcium responses in dendrites of hippocampal oriens Alveus interneurons
    Journal of Neurophysiology, 2001
    Co-Authors: Christine E Gee, Gavin L Woodhall, Jeanclaude Lacaille
    Abstract:

    Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels ([Ca2+]i) in interneurons of stratum oriens/Alveus (OA) of the hippocampus. We examined th...

Chris J Mcbain - One of the best experts on this subject based on the ideXlab platform.

  • the hyperpolarization activated current ih and its contribution to pacemaker activity in rat ca1 hippocampal stratum oriens Alveus interneurones
    The Journal of Physiology, 1996
    Co-Authors: Gianmaria Maccaferri, Chris J Mcbain
    Abstract:

    1. The hyperpolarization-activated current (Ih) and its role in pacemaking activity in rat hippocampal stratum oriens-Alveus interneurones was studied using whole-cell and perforated patch-clamp configurations. 2. Voltage-clamp recordings revealed Ih as a slowly activating, inward current, activated by hyperpolarizing steps (holding potential, Vh = -40 mV), with a reversal potential close to -30 mV. Its activation curve ranged from approximately -50 to -120 mV with a mid-activation point of -84.1 mV. 3. Ih was blocked by external application of Cs+ (2-5 mM) and ZD7288 (100 microM), but not by Ba2+ (1 mM). 4. Ih was potentiated by both noradrenaline and isoprenaline by a mechanism consistent with a shift in the Ih activation curve. 5. Under current-clamp conditions (Vh = -60 mV), ZD7288 induced a membrane hyperpolarization concomitant with an increase in the membrane input resistance and abolished the voltage sag generated by hyperpolarizing current injection. 6. Analysis of the current-discharge relationship revealed that block of Ih differentially increased the firing frequency of spikes occurring early in the train compared with those occurring late in the discharge. 7. When applied to spontaneously firing cells, ZD7288 reduced the firing frequency by selectively altering the time course of the interspike interval, while minimally affecting other action potential characteristics. Similarly, isoprenaline increased the spontaneous firing frequency by an effect exclusively on the after-hyperpolarization and interspike interval. 8. These results provide evidence for the involvement of Ih in the excitability and generation of spontaneous firing in hippocampal stratum oriens-Alveus interneurones.

  • voltage gated potassium currents in stratum oriens Alveus inhibitory neurones of the rat ca1 hippocampus
    The Journal of Physiology, 1995
    Co-Authors: Li Zhang, Chris J Mcbain
    Abstract:

    1. Voltage-activated K+ currents were recorded from visually identified inhibitory interneurones of the CA1 stratum oriens-Alveus region in neonatal rat hippocampal slices using outside-out patch and whole-cell voltage clamp techniques. 2. Outward currents comprised both a transient and a sustained component when elicited from a holding potential of -90 mV. Tail current analysis of current reversal potentials showed that outward currents were carried by potassium ions. 3. The transient current, IA, was activated with a time to peak within 5 ms, inactivated with a time constant of approximately 15 ms at 0 mV and possessed half-activation at -14 mV. Half-inactivation of the transient current occurred at -71 mV. At -90 mV, the transient current recovered from inactivation with a time constant of 142 ms. 4. Activation of currents from a holding potential of -50 mV permitted isolation of the sustained current, IK. In Ca(2+)-free conditions the sustained current showed rapid activation, reaching about 80% of its maximum within 1.5 ms, and showed little inactivation during 1 s depolarizing steps. The majority of sustained outward currents showed no voltage-dependent inactivation. In approximately 20% of cells, a slow time-dependent inactivation of the sustained current was observed, suggesting the presence of a second type of sustained current in these cells. 5. A Ca(2+)-dependent K+ current comprised a significant portion of the total sustained current; this current was activated at voltages positive to -30 mV and showed no time-dependent inactivation over a 1 s depolarizing step. This current component was removed in Ca(2+)-free conditions or by iberiotoxin. 6. Low concentrations of 4-AP (50 microM) attenuated both the transient and sustained current components recorded in a Ca(2+)-free solution. Higher concentrations of 4-AP (< 10 mM) were without further effect on the sustained current but completely blocked the transient current with an IC50 of 1.8 mM. TEA blocked the sustained current with an IC50 of 7.9 mM without significantly reducing the transient current. Both current components were resistant to dendrotoxin (500 nM).

  • passive propagation of ltd to stratum oriens Alveus inhibitory neurons modulates the temporoammonic input to the hippocampal ca1 region
    Neuron, 1995
    Co-Authors: Gianmaria Maccaferri, Chris J Mcbain
    Abstract:

    Excitatory synaptic activity in horizontal stratum oriens-Alveus interneurons (OAIs) is driven by the recurrent collaterals of CA1 pyramidal cells and is strongly influenced by protocols that elicit synaptic plasticity in these principal neurons. Induction of LTD in the Schaffer collateral-CA1 pyramidal neuron synapse causes a passive down-regulation of stratum radiatum-evoked excitatory synaptic responses onto OAIs. In addition, we show that the strength of the temporoammonic input to the CA1 pyramidal neuron distal dendrites is regulated by OAI activity. The passive propagation of LTD to OAIs consequently disinhibits the direct entorhinal cortex-CA1 input, resulting in an enhanced excitation of CA1 pyramidal neurons by a mechanism not requiring activation of the trisynaptic pathway.

Christine E Gee - One of the best experts on this subject based on the ideXlab platform.

  • group i metabotropic glutamate receptor actions in oriens Alveus interneurons of rat hippocampal ca1 region
    Brain Research, 2004
    Co-Authors: Christine E Gee, Jeanclaude Lacaille
    Abstract:

    Abstract Group I metabotropic glutamate receptors (mGluRs) are important for hippocampal interneuron function. We used whole-cell recording and confocal imaging to characterize group I mGluR actions in CA1 oriens/Alveus interneurons in slices. In tetrodotoxin and ionotropic glutamate receptor antagonists, the group I mGluR specific agonist DHPG increased intradendritic Ca2+ levels and depolarized interneurons, whereas the group II mGluR specific agonist DCG-IV and the group III mGluR specific agonist L -AP4 did not. DHPG-induced depolarizing and Ca2+ responses were antagonized by the group I mGluR antagonist 4CPG, but only Ca2+ responses were significantly inhibited by the mGluR1 antagonist CPCCOEt. DHPG-induced depolarizing responses were not blocked by the inositol-1,4,5-trisphosphate (IP3) receptor inhibitor heparin, the protein kinase C (PKC) antagonists GF-109203X, or the inhibitor of phospholipase C (PLC) U73122. Thus, these responses to DHPG may not be transduced by the PLC→IP3/diacylglycerol (DAG) pathway classically linked to group I mGluRs. DHPG-induced depolarizations were not blocked by intracellular GDPβS or bath-application of N-ethylmaleimide (NEM), suggesting the involvement of a G protein-independent pathway. Our findings indicate that group I mGluRs induce a depolarization of oriens/Alveus interneurons via a G protein-independent mechanism different from their classic signalling pathway. Since depolarizations are associated with intracellular Ca2+ rises, these actions may be important for their synaptic plasticity and vulnerability to excitotoxicity.

  • synaptically activated calcium responses in dendrites of hippocampal oriens Alveus interneurons
    Journal of Neurophysiology, 2001
    Co-Authors: Christine E Gee, Gavin L Woodhall, Jeanclaude Lacaille
    Abstract:

    Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels ([Ca2+]i) in interneurons of stratum oriens/Alveus (OA) of the hippocampus. We examined th...

  • membrane potential and intracellular ca2 oscillations activated by mglurs in hippocampal stratum oriens Alveus interneurons
    Journal of Neurophysiology, 1999
    Co-Authors: Gavin L Woodhall, Christine E Gee, Richard Robitaille, Jeanclaude Lacaille
    Abstract:

    Woodhall, Gavin, Christine E. Gee, Richard Robitaille, and Jean-Claude Lacaille. Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/Alveus inte...

Aristotle N Voineskos - One of the best experts on this subject based on the ideXlab platform.

  • manual segmentation of the fornix fimbria and Alveus on high resolution 3t mri application via fully automated mapping of the human memory circuit white and grey matter in healthy and pathological aging
    NeuroImage, 2016
    Co-Authors: Robert S C Amaral, Min Tae M Park, Gabriel A Devenyi, Vivian Lynn, Jon Pipitone, Julie L Winterburn, Sofia Chavez, Mark M Schira, Nancy J Lobaugh, Aristotle N Voineskos
    Abstract:

    Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (Alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the Alveus and cornu ammonis (CA) 1 were well preserved (all p's<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the Alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required.

  • manual segmentation of the fornix fimbria and Alveus on high resolution 3t mri application via fully automated mapping of the human memory circuit white and grey matter in healthy and pathological aging
    NeuroImage, 2016
    Co-Authors: Robert S C Amaral, Min Tae M Park, Gabriel A Devenyi, Vivian Lynn, Jon Pipitone, Julie L Winterburn, Sofia Chavez, Mark M Schira, Nancy J Lobaugh, Aristotle N Voineskos
    Abstract:

    Abstract Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (Alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases . Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the Alveus and cornu ammonis (CA) 1 were well preserved (all p's

Gavin L Woodhall - One of the best experts on this subject based on the ideXlab platform.