Hippocampal Interneurons Express a Novel Form of Synaptic Plasticity

Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Neuron (Impact Factor: 15.05). 03/1997; 18(2):295-305. DOI: 10.1016/S0896-6273(00)80269-X
Source: PubMed


Individual GABAergic interneurons in hippocampus can powerfully inhibit more than a thousand excitatory pyramidal neurons. Therefore, control of interneuron excitability provides control over hippocampal networks. We have identified a novel mechanism in hippocampus that weakens excitatory synapses onto GABAergic interneurons. Following stimulation that elicits long-term potentiation at neighboring synapses onto excitatory cells, excitatory synapses onto inhibitory interneurons undergo a long-term synaptic depression (interneuron LTD; iLTD). Unlike most other forms of hippocampal synaptic plasticity, iLTD is not synapse specific: stimulation of an afferent pathway triggers depression not only of activated synapses but also of inactive excitatory synapses onto the same interneuron. These results suggest that high frequency afferent activity increases hippocampal excitability through a dual mechanism, simultaneously potentiating synapses onto excitatory neurons and depressing synapses onto inhibitory neurons.

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Available from: Lori Mcmahon, Aug 29, 2014
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    • "Therefore, we conclude that this potentiation is a real synaptic change induced by CSD, as suggested previously [13] [18]. Although there are several physiological processes that could explain the potentiation data, we think that two types of mechanisms deserve special attention, namely mechanisms that involve the activation of glutamatergic synapses [5] and disinhibition mechanisms that act on inhibitory synapses [19]. These mechanisms are not necessarily mutually exclusive; rather, they could act independently, but this requires further investigation. "
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    ABSTRACT: Cortical spreading depression (CSD) is characterized by reversible reduction of spontaneous and evoked electrical activity of the cerebral cortex. Experimental evidence suggests that CSD may modulate neural excitability and synaptic activity, with possible implications for long-term potentiation. Systemic factors like anesthetics and insulin-induced hypoglycemia can influence CSD propagation. In this study, we examined whether the post-CSD ECoG potentiation can be modulated by anesthetics and insulin-induced hypoglycemia. We found that awake adult rats displayed increased ECoG potentiation after CSD, as compared with rats under urethane+chloralose anesthesia or tribromoethanol anesthesia. In anesthetized rats, insulin-induced hypoglycemia did not modulate ECoG potentiation. Comparison of two cortical recording regions in awake rats revealed a similarly significant (p <0.05) potentiation effect in both regions, whereas in the anesthetized groups the potentiation was significant only in the recording region nearer to the stimulating point. Our data suggest that urethane+chloralose and tribromoethanol anesthesia modulate the post-CSD potentiation of spontaneous electrical activity in the adult rat cortex, and insulin-induced hypoglycemia does not modify this effect. Data may help to gain a better understanding of excitability-dependent mechanisms underlying CSD-related neurological diseases. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Feb 2015 · Neuroscience Letters
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    • "This has been reported in CA1 FS cells (Wang and Kelly, 2001), and in stratum radiatum interneurons in CA3 (Laezza and Dingledine, 2004) and CA1 (Lamsa et al., 2005). High frequency (100e200 Hz) tetanic stimulation has however been reported to have variable effects, including either LTP in CA3 and CA1 RSNP interneurons (Christie et al., 2000; Lamsa et al., 2007a) and LTD (McMahon and Kauer, 1997). LTS interneurons in the somatosensory cortex exhibit spike timing NMDAR-dependent LTP when the pyramidal neuron spikes before the interneuron (Lu et al., 2007), which is consistent with pre-before-post STDP rules usually observed in pyramidal neurons. "
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    ABSTRACT: NMDA receptors have been known to play a central role in long-term potentiation at glutamatergic synapses in principal cells for thirty years. In contrast, their roles in the development and activity-dependent plasticity of synapses in inhibitory circuits have only recently begun to be understood. Progress has, to a great extent, been hampered by the extensive diversity of GABAergic cell types in the CNS. However, anatomical, immunohistochemical and electrophysiological methods have allowed distinct types to be identified, with the result that consistent patterns of synaptic plasticity have begun to emerge. This review summarises recent evidence on the role of NMDA receptors in the development and plasticity at GABAergic synapses on principal cells and at glutamatergic synapses on identified interneurons. A major challenge is to understand how NMDA receptors affect the routing of information in healthy inhibitory circuits, and how changes in NMDA receptor function may contribute to altered circuit function in disorders such as schizophrenia. This article is part of a Special Issue entitled "Glutamate receptor-dependent synaptic plasticity".
    Full-text · Article · Mar 2013 · Neuropharmacology
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    • "LTD of glutamatergic inputs onto hippocampal interneurons can also be triggered by several induction protocols (McMahon and Kauer, 1997; Laezza et al., 1999; Gibson et al., 2008; Nissen et al., 2010; Le Duigou et al., 2011; Edwards et al., 2012). When tested, LTD in cortical GABAergic interneurons was found to be insensitive to treatment with CB 1 antagonists (Lu et al., 2007; Gibson et al., 2008; Edwards et al., 2010; Le Duigou et al., 2011), which was surprising, because synthetic cannabinoid ligands effectively suppress excitatory inputs onto hippocampal interneurons including fast-spiking basket cells (Gibson et al., 2008; Holderith et al., 2011). "
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    ABSTRACT: Although endocannabinoids have emerged as essential retrograde messengers in several forms of synaptic plasticity, it remains controversial whether they mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and somatostatin/metabotropic glutamate receptor 1(a) (mGlu(1a))-positive GABAergic interneurons express diacylglycerol lipase-α (DGL-α), a synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than principal cells. Moreover, this lipase accumulates postsynaptically around afferent excitatory synapses in all three cell types. To address the role of retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by postsynaptic spiking paired with subsequent presynaptic stimulation or (2) induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). Neither form of LTD was evoked in the presence of the mGlu(5) antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the intracellularly applied Ca(2+) chelator BAPTA in CA1 pyramidal cells, fast-spiking interneurons (representing parvalbumin-containing cells) and interneurons projecting to stratum lacunosum-moleculare (representing somatostatin/mGlu(1a)-expressing interneurons). Both forms of LTD were completely absent in CB(1) cannabinoid receptor knock-out mice, whereas pharmacological blockade of CB(1) led to inconsistent results. Notably, in accordance with their lower DGL-α level, a higher stimulation frequency or higher DHPG concentration was required for LTD induction in interneurons compared with pyramidal cells. These findings demonstrate that hippocampal principal cells and interneurons produce endocannabinoids to mediate LTD in a qualitatively similar, but quantitatively different manner. The shifted induction threshold implies that endocannabinoid-LTD contributes to cortical information processing during distinct network activity patterns in a cell type-specific manner.
    Full-text · Article · Oct 2012 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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