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.

Hikaru genki protein is secreted into synaptic clefts from an early stage of synapse formation in Drosophila

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 589-597 ◽  
Author(s):  
M. Hoshino ◽  
E. Suzuki ◽  
Y. Nabeshima ◽  
C. Hama
Keyword(s):  
Critical Period ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Motor Behavior ◽  
Early Stage ◽  
Axon Growth ◽  
Number Of Factors ◽  
Protein Functions ◽  
Abnormal Motor ◽  
Immunohistochemical Analyses

The development of neural circuits is regulated by a large number of factors that are localized at distinct neural sites. We report here the localization of one of these factors, hikaru genki (hig) protein, at synaptic clefts in the pupal and adult nervous systems of Drosophila. In hig mutants, unusually frequent bursting activity of the muscles and abnormal motor behavior during the adult stage suggest the misfunction of neuromuscular circuitry. Our immunohistochemical analyses revealed that hig protein, produced by neurons, is secreted from the presynaptic terminals into the spaces between the presynaptic and postsynaptic terminals. In addition, we have found that the localization of this protein in the synaptic spaces temporally correlates with its functional requirement during a critical period that occurs in the middle stage of pupal formation, a period when a number of dendrite and axon growth cones meet to form synapses. These findings indicate that hig protein functions in the formation of functional neural circuits from the early stages of synapse formation.

scholarly journals Astrocytic Factors Controlling Synaptogenesis: A Team Play

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2173
Author(s):  
Giuliana Fossati ◽  
Michela Matteoli ◽  
Elisabetta Menna
Keyword(s):  
Synaptic Plasticity ◽  
Critical Period ◽  
Synapse Formation ◽  
Brain Regions ◽  
Brain Areas ◽  
Astrocyte Heterogeneity ◽  
Formation Function ◽  
Circuit Development ◽  
Brain Circuit ◽  
Neuropsychiatric Conditions

Astrocytes are essential players in brain circuit development and homeostasis, controlling many aspects of synapse formation, function, plasticity and elimination both during development and adulthood. Accordingly, alterations in astrocyte morphogenesis and physiology may severely affect proper brain development, causing neurological or neuropsychiatric conditions. Recent findings revealed a huge astrocyte heterogeneity among different brain areas, which is likely at the foundation of the different synaptogenic potential of these cells in selected brain regions. This review highlights recent findings on novel mechanisms that regulate astrocyte-mediated synaptogenesis during development, and the control of synapse number in the critical period or upon synaptic plasticity.

scholarly journals An NMDA receptor-dependent mechanism for subcellular segregation of sensory inputs in the tadpole optic tectum

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ali S Hamodi ◽  
Zhenyu Liu ◽  
Kara G Pratt
Keyword(s):  
Nmda Receptor ◽  
Ab Initio ◽  
Optic Tectum ◽  
Critical Period ◽  
Sensory Inputs ◽  
Independent Process ◽  
Circuit Development ◽  
Activity Dependent ◽  
Tectal Neuron ◽  
Dependent Mechanism

In the vertebrate CNS, afferent sensory inputs are targeted to specific depths or layers of their target neuropil. This patterning exists ab initio, from the very beginning, and therefore has been considered an activity-independent process. However, here we report that, during circuit development, the subcellular segregation of the visual and mechanosensory inputs to specific regions of tectal neuron dendrites in the tadpole optic tectum requires NMDA receptor activity. Blocking NMDARs during the formation of these sensory circuits, or removing the visual set of inputs, leads to less defined segregation, and suggests a correlation-based mechanism in which correlated inputs wire to common regions of dendrites. This can account for how two sets of inputs form synapses onto different regions of the same dendrite. Blocking NMDA receptors during later stages of circuit development did not disrupt segregation, indicating a critical period for activity-dependent shaping of patterns of innervation.

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 The activity-dependent transcription factor Npas4 regulates IQSEC3 expression in somatostatin interneurons to mediate anxiety-like behavior

2019 ◽  
Author(s):  
Seungjoon Kim ◽  
Dongseok Park ◽  
Jinhu Kim ◽  
Dongsoo Lee ◽  
Dongwook Kim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Dominant Negative ◽  
Normal Brain ◽  
Gabaergic Synapse ◽  
Iq Motif ◽  
Brain Functions ◽  
Activity Dependent ◽  
Gabaergic Synaptic Transmission

AbstractOrganization of mammalian inhibitory synapses is thought to be crucial for normal brain functions, but the underlying molecular mechanisms have been still incompletely understood. IQSEC3 (IQ motif and Sec7 domain 3) is a guanine nucleotide exchange factor for ADP-ribosylation factor (ARF-GEF) that directly interacts with gephyrin. Here, we show that GABAergic synapse-specific transcription factor, Npas4 (neuronal PAS domain protein 4) directly binds to the promoter of Iqsec3 and regulates its transcription. Strikingly, an enriched environment (EE) induced Npas4 upregulation and concurrently increased IQSEC3 protein levels specifically in mouse CA1 stratum oriens layer somatostatin (SST)-expressing GABAergic interneurons, which are compromised in Npas4-knockout (KO) mice. Moreover, expression of wild-type (WT) IQSEC3, but not a dominant-negative (DN) ARF-GEF–inactive mutant, rescued the decreased GABAergic synaptic transmission in Npas4-deficient SST interneurons. Concurrently, expression of IQSEC3 WT normalized the altered GABAergic synaptic transmission in dendrites, but not soma, of Npas4-deficient CA1 pyramidal neurons. Furthermore, expression of IQSEC3 WT, but not IQSEC3 DN, in SST-expressing interneurons in CA1 SST Npas4-KO mice rescued the altered anxiety-like behavior. Collectively, our results suggest that IQSEC3 is a key GABAergic synapse component that is directed by Npas4 activity- and ARF activity-dependent gene programs in SST-expressing interneurons to orchestrate the functional excitation-to-inhibition balance.

Liprin-α proteins: scaffold molecules for synapse maturation

2007 ◽  
Vol 35 (5) ◽  
pp. 1278-1282 ◽  
Author(s):  
S.A. Spangler ◽  
C.C. Hoogenraad
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Synaptic Proteins ◽  
Model Systems ◽  
Scaffolding Proteins ◽  
Synapse Maturation ◽  
Biochemical Genetic ◽  
Processing And Storage ◽  
And Function ◽  
And Storage

Synapses are specialized communication junctions between neurons whose plasticity provides the structural and functional basis for information processing and storage in the brain. Recent biochemical, genetic and imaging studies in diverse model systems are beginning to reveal the molecular mechanisms by which synaptic vesicles, ion channels, receptors and other synaptic components assemble to make a functional synapse. Recent evidence has shown that the formation and function of synapses are critically regulated by the liprin-α family of scaffolding proteins. The liprin-αs have been implicated in pre- and post-synaptic development by recruiting synaptic proteins and regulating synaptic cargo transport. Here, we will summarize the diversity of liprin binding partners, highlight the factors that control the function of liprin-αs at the synapse and discuss how liprin-α family proteins regulate synapse formation and synaptic transmission.

scholarly journals The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jie Gao ◽  
Mate Marosi ◽  
Jinkuk Choi ◽  
Jennifer M Achiro ◽  
Sangmok Kim ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Neural Circuits ◽  
Barrel Cortex ◽  
Hippocampal Slices ◽  
E3 Ubiquitin Ligase ◽  
Protein Levels ◽  
Synaptic Circuits ◽  
Constitutive Overexpression ◽  
Synapse Maturation ◽  
Activity Dependent

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits.

scholarly journals A new organotypic model of synaptic competition reveals activity-dependent localization of C1q

2017 ◽  
Author(s):  
Ryuta Koyama ◽  
Yuwen Wu ◽  
Allison R. Bialas ◽  
Andrew Thompson ◽  
Christina A. Welsh ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Ex Vivo ◽  
Molecular Pathways ◽  
Synapse Elimination ◽  
Synaptic Competition ◽  
Coculture Model ◽  
First Time ◽  
Activity Dependent

AbstractImmature neural circuits undergo synaptic refinement, in which activity-dependent competition between synapses results in pruning of inappropriate connections and maintenance of appropriate ones. A longstanding question is how neuronal activity eliminates specific synapses based on their strength. The technical challenges of in vivo studies have made it difficult to identify a molecular link between decreased activity and synapse elimination. We developed an organotypic coculture model of the mouse retinogeniculate system that facilitates real-time imaging and elucidation of molecular mechanisms underlying the removal of less active synapses during synaptic competition. Using this model we show for the first time that complement component C1q is necessary for activity-dependent synaptic competition and preferentially localizes to less active, competing presynaptic inputs. In conjunction with classic in vivo and ex vivo models, this coculture model is a new tool to reveal molecular pathways underlying CNS circuit refinement.

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