scholarly journals Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 825
Author(s):  
Irantzu Rico-Barrio ◽  
Sara Peñasco ◽  
Leire Lekunberri ◽  
Maitane Serrano ◽  
Jon Egaña-Huguet ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Metabotropic Glutamate Receptors ◽  
Transient Receptor Potential ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Health Concern ◽  
Adolescent Male ◽  
Transient Receptor Potential Vanilloid ◽  
Group I

Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.

scholarly journals Lack of the Transient Receptor Potential Vanilloid 1 Shifts Cannabinoid-Dependent Excitatory Synaptic Plasticity in the Dentate Gyrus of the Mouse Brain Hippocampus

2021 ◽  
Vol 15 ◽  
Author(s):  
Jon Egaña-Huguet ◽  
Miquel Saumell-Esnaola ◽  
Svein Achicallende ◽  
Edgar Soria-Gomez ◽  
Itziar Bonilla-Del Río ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Transient Receptor Potential Vanilloid ◽  
Functional Changes ◽  
Nitric Oxide Signaling ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) participates in synaptic functions in the brain. In the dentate gyrus, post-synaptic TRPV1 in the granule cell (GC) dendritic spines mediates a type of long-term depression (LTD) of the excitatory medial perforant path (MPP) synapses independent of pre-synaptic cannabinoid CB1 receptors. As CB1 receptors also mediate LTD at these synapses, both CB1 and TRPV1 might be influencing the activity of each other acting from opposite synaptic sites. We tested this hypothesis in the MPP–GC synapses of mice lacking TRPV1 (TRPV1-/-). Unlike wild-type (WT) mice, low-frequency stimulation (10 min at 10 Hz) of TRPV1-/- MPP fibers elicited a form of long-term potentiation (LTP) that was dependent on (1) CB1 receptors, (2) the endocannabinoid 2-arachidonoylglycerol (2-AG), (3) rearrangement of actin filaments, and (4) nitric oxide signaling. These functional changes were associated with an increase in the maximum binding efficacy of guanosine-5′-O-(3-[35S]thiotriphosphate) ([35S]GTPγS) stimulated by the CB1 receptor agonist CP 55,940, and a significant decrease in receptor basal activation in the TRPV1-/- hippocampus. Finally, TRPV1-/- hippocampal synaptosomes showed an augmented level of the guanine nucleotide-binding (G) Gαi1, Gαi2, and Gαi3 protein alpha subunits. Altogether, the lack of TRPV1 modifies CB1 receptor signaling in the dentate gyrus and causes the shift from CB1 receptor-mediated LTD to LTP at the MPP–GC synapses.

scholarly journals Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Aisa N. Chepkova ◽  
Susanne Schönfeld ◽  
Olga A. Sergeeva
Keyword(s):  
Nitric Oxide ◽  
Synaptic Plasticity ◽  
Metabotropic Glutamate Receptors ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Striatal Slices ◽  
Expression Of Genes ◽  
Age Related ◽  
Group I

Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old) to old (18–24 months of age) animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO) synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor) was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD) and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age). Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

scholarly journals Long-term potentiation in hippocampal oriens interneurons: postsynaptic induction, presynaptic expression and evaluation of candidate retrograde factors

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130133 ◽  
Author(s):  
Elizabeth Nicholson ◽  
Dimitri M. Kullmann
Keyword(s):  
Ampa Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Potentiation ◽  
Metabotropic Glutamate ◽  
Ca1 Region ◽  
Group I ◽  
Term Potentiation ◽  
Trpv1 Receptors ◽  
Retrograde Signalling

Several types of hippocampal interneurons exhibit a form of long-term potentiation (LTP) that depends on Ca 2+ -permeable AMPA receptors and group I metabotropic glutamate receptors. Several sources of evidence point to a presynaptic locus of LTP maintenance. The retrograde factor that triggers the expression of LTP remains unidentified. Here, we show that trains of action potentials in putative oriens-lacunosum-moleculare interneurons of the mouse CA1 region can induce long-lasting potentiation of stimulus-evoked excitatory postsynaptic currents that mimics LTP elicited by high-frequency afferent stimulation. We further report that blockers of nitric oxide production or TRPV1 receptors failed to prevent LTP induction. The present results add to the evidence that retrograde signalling underlies N -methyl- d -aspartate (NMDA) receptor-independent LTP in oriens interneurons, mediated by an unidentified factor.

scholarly journals Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Heterosynaptic Plasticity ◽  
Spine Plasticity

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.

scholarly journals Long-term potentiation expands information content of hippocampal dentate gyrus synapses

2018 ◽  
Vol 115 (10) ◽  
pp. E2410-E2418 ◽  
Author(s):  
Cailey Bromer ◽  
Thomas M. Bartol ◽  
Jared B. Bowden ◽  
Dusten D. Hubbard ◽  
Dakota C. Hanka ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Storage Capacity ◽  
Unit Length ◽  
Long Term Potentiation ◽  
Information Storage ◽  
Perforant Path ◽  
Hippocampal Dentate Gyrus ◽  
Term Potentiation

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

Amyloid β Prevents Activation of Calcium/Calmodulin-Dependent Protein Kinase II and AMPA Receptor Phosphorylation During Hippocampal Long-Term Potentiation

2004 ◽  
Vol 92 (5) ◽  
pp. 2853-2858 ◽  
Author(s):  
Danyun Zhao ◽  
Joseph B. Watson ◽  
Cui-Wei Xie
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Dependent Protein Kinase ◽  
Term Potentiation ◽  
Dependent Protein ◽  
Dependent Site

Accumulation of amyloid β-peptides (Aβ) in the brain has been linked with memory loss in Alzheimer's disease and its animal models. However, the synaptic mechanism by which Aβ causes memory deficits remains unclear. We previously showed that acute application of Aβ inhibited long-term potentiation (LTP) in the hippocampal perforant path via activation of calcineurin, a Ca2+-dependent protein phosphatase. This study examined whether Aβ could also inhibit Ca2+/calmodulin dependent protein kinase II (CaMKII), further disrupting the dynamic balance between protein kinase and phosphatase during synaptic plasticity. Immunoblot analysis was conducted to measure autophosphorylation of CaMKII at Thr286 and phosphorylation of the GluR1 subunit of AMPA receptors in single rat hippocampal slices. A high-frequency tetanus applied to the perforant path significantly increased CaMKII autophosphorylation and subsequent phosphorylation of GluR1 at Ser831, a CaMKII-dependent site, in the dentate area. Acute application of Aβ1–42 inhibited dentate LTP and associated phosphorylation processes, but was without effect on phosphorylation of GluR1 at Ser845, a protein kinase A-dependent site. These results suggest that activity-dependent CaMKII autophosphorylation and AMPA receptor phosphorylation are essential for dentate LTP. Disruption of such mechanisms could directly contribute to Aβ-induced deficits in hippocampal synaptic plasticity and memory.

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