Selective Localization of Shanks to VGLUT1-Positive Excitatory Synapses in the Mouse Hippocampus

Heise, Christopher E.; Schroeder, Jan C.; Schoen, Michael; Halbedl, Sonja; Reim, Dominik; Woelfle, Sarah; Kreutz, Michael R.; Schmeißer, Michael J.; Boeckers, Tobias M.

doi:10.3389/fncel.2016.00106

Cited by 20 publications

(34 citation statements)

References 51 publications

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“…This did not reveal co-immunolabeling ( Supplementary Fig. 2b), consistent with earlier evidence for nonoverlapping distribution of vGlut1 and vGlut2 (Heise et al 2016), and demonstrating that these 2 populations of excitatory subicular neurons project onto the same superficial layers of RSC. Overall, projection from vGlut1 + and vGlut2 + neurons labeled by infusing virus with cannula into DH ( Supplementary Fig.…”

Section: Projections From Dh To Rsc Are Molecularly Distinctsupporting

confidence: 90%

Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories

et al. 2018

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Learning to associate stressful events with specific environmental contexts depends on excitatory transmission in the hippocampus, but how this information is transmitted to the neocortex for lasting memory storage is unclear. We identified dorsal hippocampal (DH) projections to the retrosplenial cortex (RSC), which arise mainly from the subiculum and contain either the vesicular glutamate transporter 1 (vGlut1) or vGlut2. Both vGlut1+ and vGlut2+ axons strongly excite and disynaptically inhibit RSC pyramidal neurons in superficial layers, but vGlut2+ axons trigger greater inhibition that spreads to deep layers, indicating that these pathways engage RSC circuits via partially redundant, partially differentiated cellular mechanisms. Using contextual fear conditioning in mice to model contextual associative memories, together with chemogenetic axonal silencing, we found that vGlut1+ projections are principally involved in processing recent context memories whereas vGlut2+ projections contribute to their long-lasting storage. Thus, within the DH→RSC pathway, engagement of vGlut1+ and vGlut2+ circuits differentially contribute to the formation and persistence of fear-inducing context memories.

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Section: Projections From Dh To Rsc Are Molecularly Distinctsupporting

confidence: 90%

Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories

et al. 2018

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“…This study utilized confocal microscopy to examine developmental SHANK1 co‐expression with various cellular markers in the hippocampus, a critical brain region for learning and memory. Consistent with numerous studies, our findings demonstrated that SHANK1 strongly co‐expressed with the dendritic marker MAP2 (Lim et al, ; Naisbitt et al, ; Hung et al, ; Heise et al, ). Furthermore, our subsequent analyses demonstrated that SHANK1 MAP2 co‐expression peaked at P15, suggesting an increased amount of SHANK1 localized to CA1 dendrites.…”

Section: Discussionsupporting

confidence: 92%

SHANK1 is differentially expressed during development in CA1 hippocampal neurons and astrocytes

Collins

Belagodu

Reed

et al. 2017

Developmental Neurobiology

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Recent studies have strongly suggested a role for the synaptic scaffolding protein SHANK1 in normal synaptic structure and signaling. Global SHANK1 knockout (SHANK1-/-) mice demonstrate reduced dendritic spine density, an immature dendritic spine phenotype and impairments in various cognitive tasks. SHANK1 overexpression is associated with increased dendritic spine size and impairments in fear conditioning. These studies suggest proper regulation of SHANK1 is crucial for appropriate synaptic structure and cognition. However, little is known regarding SHANK1's developmental expression in brain regions critical for learning. The current study quantified cell specific developmental expression of SHANK1 in the hippocampus, a brain region critically involved in various learning paradigms shown to be disrupted by SHANK1 dysregulation. Consistent with prior studies, SHANK1 was found to be strongly co-expressed with dendritic markers, with significant increased co-expression at postnatal day (P) 15, an age associated with increased synaptogenesis in the hippocampus. Interestingly, SHANK1 was also found to be expressed in astrocytes and microglia. To our knowledge, this is the first demonstration of glial SHANK1 localization; therefore, these findings were further examined via a glial purified primary cell culture fraction using magnetic cell sorting. This additional analysis further demonstrated that SHANK1 was expressed in glial cells, supporting our immunofluorescence co-expression findings. Developmentally, astroglial SHANK1 co-expression was found to be significantly elevated at P5 with a reduction into adulthood, while SHANK1 microglial co-expression did not significantly change across development. These data collectively implicate a more global role for SHANK1 in mediating normal cellular signaling in the brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 363-373, 2018.

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“…Shank2, which is mainly localized at excitatory synapses (Boeckers et al, 1999 ; Tao-Cheng et al, 2015 ; Heise et al, 2016 ), may regulate excitatory synapse formation and function in dendrites and consequently the output functions of PV-positive neurons, suggesting a potential mechanism for the resistance to PTZ-induced seizures in Pv-Cre;Shank2 fl/fl mice. Notably, excitatory transmission, neuronal firing, and inhibitory transmission to target neurons are reduced in PV-positive neurons in Shank1 global KO mice (Mao et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Shank2 Deletion in Parvalbumin Neurons Leads to Moderate Hyperactivity, Enhanced Self-Grooming and Suppressed Seizure Susceptibility in Mice

Lee

Kim

et al. 2018

Front. Mol. Neurosci.

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Shank2 is an abundant postsynaptic scaffolding protein implicated in neurodevelopmental and psychiatric disorders, including autism spectrum disorders (ASD). Deletion of Shank2 in mice has been shown to induce social deficits, repetitive behaviors, and hyperactivity, but the identity of the cell types that contribute to these phenotypes has remained unclear. Here, we report a conditional mouse line with a Shank2 deletion restricted to parvalbumin (PV)-positive neurons (Pv-Cre;Shank2fl/fl mice). These mice display moderate hyperactivity in both novel and familiar environments and enhanced self-grooming in novel, but not familiar, environments. In contrast, they showed normal levels of social interaction, anxiety-like behavior, and learning and memory. Basal brain rhythms in Pv-Cre;Shank2fl/fl mice, measured by electroencephalography, were normal, but susceptibility to pentylenetetrazole (PTZ)-induced seizures was decreased. These results suggest that Shank2 deletion in PV-positive neurons leads to hyperactivity, enhanced self-grooming and suppressed brain excitation.

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Selective Localization of Shanks to VGLUT1-Positive Excitatory Synapses in the Mouse Hippocampus

Cited by 20 publications

References 51 publications

Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories

Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories

SHANK1 is differentially expressed during development in CA1 hippocampal neurons and astrocytes

Shank2 Deletion in Parvalbumin Neurons Leads to Moderate Hyperactivity, Enhanced Self-Grooming and Suppressed Seizure Susceptibility in Mice

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