scholarly journals Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus

2021 ◽  
Vol 118 (4) ◽  
pp. e2017590118
Author(s):  
Kyle R. Jensen ◽  
Coralie Berthoux ◽  
Kaoutsar Nasrallah ◽  
Pablo E. Castillo
Keyword(s):  
Cannabinoid Receptors ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Epileptic Activity ◽  
Axon Terminals ◽  
Excitatory Transmission ◽  
Term Potentiation ◽  
Dependent Learning

Recurrent excitatory neural networks are unstable. In the hippocampus, excitatory mossy cells (MCs) receive strong excitatory inputs from dentate granule cells (GCs) and project back onto the proximal dendrites of GCs. By targeting the ipsi- and contralateral dentate gyrus (DG) along the dorsoventral axis of the hippocampus, MCs form an extensive recurrent excitatory circuit (GC-MC-GC) whose dysregulation can promote epilepsy. We recently reported that a physiologically relevant pattern of MC activity induces a robust form of presynaptic long-term potentiation (LTP) of MC-GC transmission which enhances GC output. Left unchecked, this LTP may interfere with DG-dependent learning, like pattern separation—which relies on sparse GC firing—and may even facilitate epileptic activity. Intriguingly, MC axons display uniquely high expression levels of type-1 cannabinoid receptors (CB1Rs), but their role at MC-GC synapses is poorly understood. Using rodent hippocampal slices, we report that constitutively active CB1Rs, presumably via βγ subunits, selectively inhibited MC inputs onto GCs but not MC inputs onto inhibitory interneurons or CB1R-sensitive inhibitory inputs onto GCs. Tonic CB1R activity also inhibited LTP and GC output. Furthermore, brief endocannabinoid release from GCs dampened MC-GC LTP in two mechanistically distinct ways: during induction via βγ signaling and before induction via αi/o signaling in a form of presynaptic metaplasticity. Lastly, a single in vivo exposure to exogenous cannabinoids was sufficient to induce this presynaptic metaplasticity. By dampening excitatory transmission and plasticity, tonic and phasic CB1R activity at MC axon terminals may preserve the sparse nature of the DG and protect against runaway excitation.

scholarly journals GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Mike T. Lin ◽  
Xiang-ming Zha
Keyword(s):  
Passive Avoidance ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Metabotropic Receptor ◽  
Term Potentiation

Abstract Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.

In vivo injected mitochondria-targeted plastoquinone antioxidant SkQR1 prevents β-amyloid-induced decay of long-term potentiation in rat hippocampal slices

2011 ◽  
Vol 76 (12) ◽  
pp. 1367-1370 ◽  
Author(s):  
N. A. Kapay ◽  
N. K. Isaev ◽  
E. V. Stelmashook ◽  
O. V. Popova ◽  
D. B. Zorov ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Β Amyloid

In Vivo Recordings of Long-Term Potentiation and Long-Term Depression in the Dentate Gyrus of the Neonatal Rat

2004 ◽  
Vol 91 (2) ◽  
pp. 613-622 ◽  
Author(s):  
Michael P. O'Boyle ◽  
Viet Do ◽  
Brian E. Derrick ◽  
Brenda J. Claiborne
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Neonatal Rat ◽  
Perforant Path ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Old Rats

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist ( R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.

scholarly journals Activity-dependent LTP in the dentate gyrus promotes epileptic seizures

2021 ◽  
Author(s):  
Kaoutsar Nasrallah ◽  
Maria Agustina Frechou ◽  
Young J Yoon ◽  
Subrina Persaud ◽  
Tiago Goncalves ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Focal Epilepsy ◽  
Epileptic Seizures ◽  
Long Term Potentiation ◽  
Epileptic Activity ◽  
Cellular Mechanisms ◽  
Brain Disorder ◽  
Adult Mice ◽  
Term Potentiation

Epilepsy is a devastating brain disorder whose cellular mechanisms remain poorly understood. Excitatory mossy cells (MCs) in the dentate gyrus of the hippocampus are implicated in temporal lobe epilepsy, the most common form of focal epilepsy in adults. However, the role of MCs during initial seizures, before MC loss occurs, is unclear. Here, we show that initial seizures induced with kainic acid (KA) intraperitoneal injection in adult mice, a well-established model of experimental epilepsy, not only increased MC and granule cell (GC) activity in vivo, but also triggered a BDNF-dependent long-term potentiation at MC-GC synapses (MC-GC LTP). In vivo induction of MC-GC LTP worsened KA-induced seizures, whereas selective MC silencing and Bdnf genetic removal from GCs, which abolishes LTP, were both anti-epileptic. Thus, initial seizures strengthen MC-GC synaptic transmission, thereby promoting epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help develop therapeutic strategies for early intervention.

scholarly journals Preconditioning In Vivo Ischemia Inhibits Anoxic Long-Term Potentiation and Functionally Protects CA1 Neurons in the Gerbil

1998 ◽  
Vol 18 (3) ◽  
pp. 288-296 ◽  
Author(s):  
Kensuke Kawai ◽  
Tadayoshi Nakagomi ◽  
Takaaki Kirino ◽  
Akira Tamura ◽  
Nobufumi Kawai
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Forebrain Ischemia ◽  
Term Potentiation ◽  
Induced Tolerance

Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor-mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional, and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.

scholarly journals Restoration of Long-Term Potentiation in Middle-Aged Hippocampus After Induction of Brain-Derived Neurotrophic Factor

2006 ◽  
Vol 96 (2) ◽  
pp. 677-685 ◽  
Author(s):  
Christopher S. Rex ◽  
Julie C. Lauterborn ◽  
Ching-Yi Lin ◽  
Eniko A. Kramár ◽  
Gary A. Rogers ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Aged Rats ◽  
Middle Aged ◽  
Age Related ◽  
Term Potentiation

Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.

Effects of aging on axon terminals in the dentate molecular layer

1987 ◽  
Vol 45 ◽  
pp. 928-929
Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova
Keyword(s):  
Granule Cells ◽  
Molecular Layer ◽  
Age Groups ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Perforant Path ◽  
Axon Terminals ◽  
Fischer 344 ◽  
Spatial Memory Deficit ◽  
Effects Of Aging

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.

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