scholarly journals Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit

2019 ◽  
Author(s):  
Christopher K. Salmon ◽  
Horia Pribiag ◽  
W. Todd Farmer ◽  
Scott Cameron ◽  
Emma V. Jones ◽  
...  
Keyword(s):  
Neural Activity ◽  
Pyramidal Neurons ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Reversal Potential ◽  
Glutamatergic Synapse ◽  
Inhibitory Neurotransmitter ◽  
Key Factor ◽  
Circuit Development ◽  
Activity Dependent

ABSTRACTGABA is the main inhibitory neurotransmitter in the mature brain but has the paradoxical property of depolarizing neurons during early development. Depolarization provided by GABAA transmission during this early phase regulates neural stem cell proliferation, neural migration, neurite outgrowth, synapse formation, and circuit refinement, making GABA a key factor in neural circuit development. Importantly, depending on the context, depolarizing GABAA transmission can either drive neural activity, or inhibit it through shunting inhibition. The varying roles of depolarizing GABAA transmission during development, and its ability to both drive and inhibit neural activity, makes it a difficult developmental cue to study. This is particularly true in the later stages of development, when the majority of synapses form and GABAA transmission switches from depolarizing to hyperpolarizing. Here we addressed the importance of depolarizing but inhibitory (or shunting) GABAA transmission in glutamatergic synapse formation in hippocampal CA1 pyramidal neurons. We first showed that the developmental depolarizing-to-hyperpolarizing switch in GABAA transmission is recapitulated in organotypic hippocampal slice cultures. Based on the expression profile of K+-Cl- co-transporter 2 (KCC2) and changes in the GABA reversal potential, we pinpointed the timing of the switch from depolarizing to hyperpolarizing GABAA transmission in CA1 neurons. We found that blocking depolarizing but shunting GABAA transmission increased excitatory synapse number and strength, indicating that depolarizing GABAA transmission can restrain glutamatergic synapse formation. The increase in glutamatergic synapses was activity-dependent, but independent of BDNF signalling. Importantly, the elevated number of synapses was stable for more than a week after GABAA inhibitors were washed out. Together these findings point to the ability of immature GABAergic transmission to restrain glutamatergic synapse formation and suggest an unexpected role for depolarizing GABAA transmission in shaping excitatory connectivity during neural circuit development.

scholarly journals Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
Joshua Titlow ◽  
Francesca Robertson ◽  
Aino Järvelin ◽  
David Ish-Horowicz ◽  
Carlas Smith ◽  
...  
Keyword(s):  
Single Molecule ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Synapse Formation ◽  
Long Distance ◽  
Key Factor ◽  
Larval Neuromuscular Junction ◽  
Rnp Granules ◽  
Activity Dependent

Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.

scholarly journals Syncrip/hnRNPQ is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation

2019 ◽  
Author(s):  
Josh Titlow ◽  
Francesca Robertson ◽  
Aino Järvelin ◽  
David Ish-Horowicz ◽  
Carlas Smith ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Single Molecule ◽  
Rna Binding ◽  
Synapse Formation ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Long Distance ◽  
Key Factor ◽  
Activity Dependent

AbstractMemory and learning involve activity-driven expression of proteins and cytoskeletal reorganisation at new synapses, often requiring post-transcriptional regulation a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organises actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is not yet known. Here, we show that the local translation of msp300 is promoted during activity-dependent plasticity by the conserved RNA binding protein Syncrip/hnRNP Q, which binds to msp300 transcripts and is essential for plasticity. Single molecule imaging shows that Syncrip is associated in vivo with msp300 mRNA in ribosome-rich particles. Elevated neural activity alters the dynamics of Syncrip RNP granules at the synapse, suggesting a change in particle composition or binding that facilitates translation. These results introduce Syncrip as an important early-acting activity-dependent translational regulator of a plasticity gene that is strongly associated with human ataxias.Syncrip regulates synaptic plasticity via msp300Titlow et al. find that Syncrip (hnRNPQ RNA binding protein) acts directly on msp300 to modulate activity-dependent synaptic plasticity. In vivo biophysical experiments reveal activity-dependent changes in RNP complex sizes compatible with an increase in translation at the synapse.

scholarly journals Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

2021 ◽  
Author(s):  
TSUYOSHI HATTORI ◽  
Stanislav M Cherepanov ◽  
Ryo Sakaga ◽  
Jureepon Roboon ◽  
Dinh Thi Nguyen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Medial Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Social Memory ◽  
Behavioral Abnormalities ◽  
Survival And Reproduction

Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

scholarly journals Depolarizing GABA Transmission Restrains Activity-Dependent Glutamatergic Synapse Formation in the Developing Hippocampal Circuit

2020 ◽  
Vol 14 ◽  
Author(s):  
Christopher K. Salmon ◽  
Horia Pribiag ◽  
Claire Gizowski ◽  
W. Todd Farmer ◽  
Scott Cameron ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Glutamatergic Synapse ◽  
Gaba Transmission ◽  
Activity Dependent

scholarly journals Molecular Mechanisms Underlying Activity-Dependent GABAergic Synapse Development and Plasticity and Its Implications for Neurodevelopmental Disorders

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Bidisha Chattopadhyaya
Keyword(s):  
Neurodevelopmental Disorders ◽  
Critical Period ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Normal Function ◽  
Gabaergic Synapse ◽  
Synapse Maturation ◽  
Circuit Development ◽  
Activity Dependent

GABAergic interneurons are critical for the normal function and development of neural circuits, and their dysfunction is implicated in a large number of neurodevelopmental disorders. Experience and activity-dependent mechanisms play an important role in GABAergic circuit development, also recent studies involve a number of molecular players involved in the process. Emphasizing the molecular mechanisms of GABAergic synapse formation, in particular basket cell perisomatic synapses, this paper draws attention to the links between critical period plasticity, GABAergic synapse maturation, and the consequences of its dysfunction on the development of the nervous system.

scholarly journals Spatial and Temporal Dynamics in the Ionic Driving Force for GABAAReceptors

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
R. Wright ◽  
J. V. Raimondo ◽  
C. J. Akerman
Keyword(s):  
Driving Force ◽  
Neural Circuit ◽  
Temporal Dynamics ◽  
Spatial And Temporal Dynamics ◽  
Mature Brain ◽  
Gabaergic Synapses ◽  
Circuit Development ◽  
And Function ◽  
Activity Dependent

It is becoming increasingly apparent that the strength of GABAergic synaptic transmission is dynamic. One parameter that can establish differences in the actions of GABAergic synapses is the ionic driving force for the chloride-permeable GABAAreceptor (GABAAR). Here we review some of the sophisticated ways in which this ionic driving force can vary within neuronal circuits. This driving force for GABAARs is subject to tight spatial control, with the distribution of Cl−transporter proteins and channels generating regional variation in the strength of GABAAR signalling across a single neuron. GABAAR dynamics can result from short-term changes in their driving force, which involve the temporary accumulation or depletion of intracellular Cl−. In addition, activity-dependent changes in the expression and function of Cl−regulating proteins can result in long-term shifts in the driving force for GABAARs. The multifaceted regulation of the ionic driving force for GABAARs has wide ranging implications for mature brain function, neural circuit development, and disease.

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