Long-term Depression In Dentate Gyrus Research Articles

Endocannabinoid receptors contribute significantly to multiple forms of long-term depression in the rat dentate gyrus.

Cannabinoid receptors are widely expressed throughout the hippocampal formation, but are particularly dense in the dentate gyrus (DG) subregion. We, and others, have shown in mice that cannabinoid type 1 receptors (CB1Rs) are involved in a long-term depression (LTD) that can be induced by prolonged 10 Hz stimulation of the medial perforant path (MPP)-granule cell synaptic input to the DG. Here, we extend this work to examine the involvement of CB1Rs in other common forms of LTD in the hippocampus of juvenile male and female Sprague–Dawley rats (Rattus norvegicus). We found, as in mice, that prolonged 10 Hz stimulation (6000 pulses) could reliably induce a form of LTD that was dependent upon CB1R activation. In addition, we also discovered a role for both CB1R and mGluR proteins in LTD induced with 1 Hz low-frequency stimulation (1 Hz-LTD; 900 pulses) and in LTD induced by bath application of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG; DHPG-LTD). This study elucidates an essential role for endocannabinoid receptors in a number of forms of LTD in the rat DG, and identifies a novel role for CB1Rs as potential therapeutic targets for conditions that involve impaired LTD in the DG.

Differential effects of strain, circadian cycle, and stimulation pattern on LTP and concurrent LTD in the dentate gyrus of freely moving rats

Because long-term potentiation (LTP) and long-term depression (LTD) are thought to be involved in learning and memory, it is important to delineate factors that modulate their induction and persistence, especially as studied in freely moving animals. Here, we investigated the effects of rat strain, circadian cycle, and high-frequency stimulation (HFS) pattern on LTP and concurrently induced LTD in the dentate gyrus (DG). Comparison of two commonly used rat strains revealed that medial perforant path field EPSP-population spike (E-S) coupling and LTP were greater in Long-Evans than Sprague-Dawley rats. Circadian cycle experiments conducted in Long-Evans rats revealed greater E-S coupling and enhanced LTP during the dark phase. Interestingly, concurrent LTD in the lateral perforant path did not significantly differ across strains or circadian cycle. Testing HFS protocols during the dark phase revealed that theta burst stimulation (100 Hz bursts at 5 Hz intervals) was ineffective in eliciting either LTP or concurrent LTD in DG, whereas 400 Hz bursts delivered at theta (5 Hz) or delta (1 Hz) frequencies produced substantial LTP and concurrent LTD. Thus, these natural and experimental factors regulate granule cell excitability, and differentially affect LTP and concurrent LTD in the DG of freely moving rats. © 2011 Wiley Periodicals, Inc.

Brief neck restraint stress enhances long-term potentiation and suppresses long-term depression in the dentate gyrus of the mouse

We studied the effects of brief (10min) neck restraint on long-term potentiation (LTP) and long-term depression (LTD) in mouse dentate gyrus (DG) slices. Brain slices were prepared immediately after neck restraint and LTP/LTD induction was attempted 3.5h later. LTP enhancement and LTD suppression was observed in slices prepared from stressed animals. The corticosterone plasma concentration was elevated approx. fourfold just after the neck restraint session. To examine the role of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in mediating the effects of neck restraint on LTP and LTD, the animals were pretreated with either the specific GR antagonist RU38486, the specific MR antagonist spironolactone, the corticosterone synthesis inhibitor metyrapone, or vehicle Tween 80. Injection with Tween 80 and subsequent neck restraint did not influence LTP enhancement or LTD suppression, but the effects of neck restraint were prevented by RU38486, spironolactone and metyrapone pretreatment. These data indicate that acute stress caused by brief neck restraint enhances LTP and impairs LTD in the dentate gyrus and that these effects are mediated by activation of GRs and MRs.

TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus

The transient receptor potential TRPV1 is a nonselective cation channel that mediates pain sensations and is commonly activated by a wide variety of exogenous and endogenous, physical and chemical stimuli. While TRPV1 receptors are mainly found in nociceptive neurons of the peripheral nervous system, these receptors have also been described in the brain where their role is far less understood. Activation of TRPV1 reportedly regulates neurotransmitter release at several central synapses. Here we show, however, that TRPV1 suppresses excitatory transmission in rat and mouse dentate gyrus by regulating postsynaptic function in an input-specific manner. This suppression is due to a Ca2+-calcineurin and clathrin-dependent internalization of AMPA receptors. Moreover, synaptic activation of TRPV1 triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamide in a type 1 cannabinoid receptor-independent manner. Thus, our findings reveal a novel form of endocannabinoid- and TRPV1-mediated regulation of synaptic strength at central synapses.

Differential Effect of TEA on Long-Term Synaptic Modification in Hippocampal CA1 and Dentate Gyrus in vitro

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni2+ (50 μM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni2+ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 μM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni2+. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni2+. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.