Synaptic strength at the temporoammonic input to the hippocampal CA1 region in vivo is regulated by NMDA receptors, metabotropic glutamate receptors and voltage-gated calcium channels

Aksoy‐Aksel, Ayla; Manahan‐Vaughan, Denise

doi:10.1016/j.neuroscience.2015.03.014

Cited by 14 publications

(10 citation statements)

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“…In ATRX‐cKO mice, MPP‐evoked E1 response reached peak potentiation of ~110% at 45–75 min post‐TBS (Figure c, right), likely resulting from the combination of a slowly rising E1 and a shorter duration of LTP. A gradual rise in MPP‐evoked E1 response after TBS has not been reported before (Aksoy‐Aksel & Manahan‐Vaughan, ; Remondes & Schuman, ). It might be related to a protein‐synthesis‐dependent late LTP (Remondes & Schuman, ), although this remains to be demonstrated experimentally.…”

Section: Discussionmentioning

confidence: 70%

“…Moreover, LTP at apical and basal dendritic synapses has different properties and molecular modulation (Brzdak et al, ; Leung & Shen, ). For instance, proximal apical and basal dendritic LTP have different sensitivities to D4 receptor activation (Li et al, ) and NMDA receptor blockade (Leung & Shen, ), while distal apical dendritic LTP has a dual dependence on L‐type voltage‐gated Ca 2+ channels and NMDA receptors (Aksoy‐Aksel & Manahan‐Vaughan, ; Remondes & Schuman, ).…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of ATRX in forebrain excitatory neurons affects hippocampal synaptic plasticity

et al. 2019

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α-Thalassemia X-linked intellectual disability (ATR-X) syndrome is a neurodevelopmental disorder caused by mutations in the ATRX gene that encodes a SNF2-type chromatinremodeling protein. The ATRX protein regulates chromatin structure and gene expression in the developing mouse brain and early inactivation leads to DNA replication stress, extensive cell death, and microcephaly. However, the outcome of Atrx loss of function postnatally in neurons is less well understood. We recently reported that conditional inactivation of Atrx in postnatal forebrain excitatory neurons (ATRX-cKO) causes deficits in long-term hippocampus-dependent spatial memory. Thus, we hypothesized that ATRX-cKO mice will display impaired hippocampal synaptic transmission and plasticity.In the present study, evoked field potentials and current source density analysis were recorded from a multichannel electrode in male, urethane-anesthetized mice. Three major excitatory synapses, the Schaffer collaterals to basal dendrites and proximal apical dendrites, and the temporoammonic path to distal apical dendrites on hippocampal CA1 pyramidal cells were assessed by their baseline synaptic transmission, including pairedpulse facilitation (PPF) at 50-ms interpulse interval, and by their long-term potentiation (LTP) induced by theta-frequency burst stimulation. Baseline single-pulse excitatory response at each synapse did not differ between ATRX-cKO and control mice, but baseline PPF was reduced at the CA1 basal dendritic synapse in ATRX-cKO mice. While basal dendritic LTP of the first-pulse excitatory response was not affected in ATRX-cKO mice, proximal and distal apical dendritic LTP were marginally and significantly reduced, respectively. These results suggest that ATRX is required in excitatory neurons of the forebrain to achieve normal hippocampal LTP and PPF at the CA1 apical and basal dendritic synapses, respectively. Such alterations in hippocampal synaptic transmission and plasticity could explain the long-term spatial memory deficits in ATRX-cKO mice and provide insight into the physiological mechanisms underlying intellectual disability in ATR-X syndrome patients.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Inactivation of ATRX in forebrain excitatory neurons affects hippocampal synaptic plasticity

et al. 2019

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“…Whether this is due to E2's effects at SC and/or TA cannot be delineated, as intra-CA1 delivery of RO via stereotaxically placed cannulas likely spreads to proximal and distal dendrites, acting at GluN2B-containing NMDARs at both sites. Electrophysiological data (Dvorak-Carbone and Schuman, 1999;Otmakhova et al, 2002;Remondes and Schuman, 2002;Aksoy-Aksel and Manahan-Vaughan, 2015) support an important role of TA synapses in gating CA1 information processing, and it is possible that changing excitability at distal dendrites leads to altered CA1 information flow which could be linked to altered learning (Vnek et al, 1995;Kirkby and Higgins, 1998;Ferbinteanu et al, 1999;Remondes and Schuman, 2004;Hunsaker et al, 2007;Vago et al, 2007;Vago and Kesner, 2008). Therefore, it is possible that a block of enhanced E2-induced NOR is due not only to enhanced GluN2B function at SC but at TA synapses as well.…”

Section: Discussionmentioning

confidence: 87%

“…Given its position in the circuit and the particular timing of activity, the TA pathway can dictate whether SC-CA1 synapses will drive CA1 pyramidal cells to spike. Additionally, TA-CA1 synapses undergo NMDAR-dependent LTP and LTD (Dvorak-Carbone and Schuman, 1999;Remondes and Schuman, 2002;Aksoy-Aksel and Manahan-Vaughan, 2015), and as such, can either enhance or prevent plasticity at CA3-CA1 synapses (Remondes and Schuman, 2002). It is currently unknown if TA-CA1 synapses are modulated by E2.…”

Section: Introductionmentioning

confidence: 99%

17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses

Smith

Bredemann

et al. 2015

Hippocampus

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When circulating 17β estradiol (E2) is elevated to proestrous levels, hippocampus-dependent learning and memory is enhanced in female rodents, nonhuman primates, and women due to heightened synaptic function at hippocampal synapses. We previously reported that proestrous-like levels of E2 administered to young adult ovariectomized (OVX) female rats increases the magnitude of LTP at CA3 Schaffer collateral (SC)-CA1 synapses only when dendritic spine density, the NMDAR/AMPAR ratio, and current mediated by GluN2B-containing NMDA receptors (NMDARs) are simultaneously increased. We also reported that this increase in GluN2B-mediated NMDAR current in area CA1 is causally related to the E2-induced increase in novel object recognition, tying together heightened synaptic function with improved learning and memory. In addition to SC inputs, innervation from the entorhinal cortex in the temporoammonic (TA) pathway onto CA1 distal dendrites in stratum lacunosum-moleculare is critical for spatial memory formation and retrieval. It is not known whether E2 modulates TA-CA1 synapses similarly to SC-CA1 synapses. Here, we report that 24 hours post-E2 injection, dendritic spine density on CA1 pyramidal cell distal dendrites and current mediated by GluN2B-containing NMDARs at TA-CA1 synapses is increased, similarly to our previous findings at SC-CA1 synapses. However, in contrast to SC-CA1 synapses, AMPAR transmission at TA-CA1 synapses is significantly increased, and there is no effect on the LTP magnitude. Pharmacological blockade of GluN2B-containing NMDARs or ERK activation, which occurs downstream of synaptic but not extrasynaptic GluN2B-containing NMDARs, attenuates the LTP magnitude only in slices from E2-treated rats. These data show that E2 recruits a causal role for GluN2B-containing NMDARs and ERK signaling in the induction of LTP, cellular mechanisms not required for LTP induction at TA-CA1 synapses in vehicle-treated OVX female rats.

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“…At some synapses, LTP is dually dependent on NMDARs and VDCCs (Aksoy-Aksel and ManahanVaughan, 2015) . Depending on the stimulation strength, hippocampus synapses are capable of exhibiting LTP that involves L-type VDCCs (Grover and Teyler, 1990, Manahan-Vaughan et al, 1998, Freir and Herron, 2003, Aksoy-Aksel and Manahan-Vaughan, 2015.…”

Section: Introductionmentioning

confidence: 99%

The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats

Komaki

Saadat

Shahidi

et al. 2017

Brain Research Bulletin

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Synaptic strength at the temporoammonic input to the hippocampal CA1 region in vivo is regulated by NMDA receptors, metabotropic glutamate receptors and voltage-gated calcium channels

Cited by 14 publications

References 46 publications

Inactivation of ATRX in forebrain excitatory neurons affects hippocampal synaptic plasticity

Inactivation of ATRX in forebrain excitatory neurons affects hippocampal synaptic plasticity

17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses

The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats

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