scholarly journals Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network

2010 ◽  
Vol 108 (1) ◽  
pp. 373-378 ◽  
Author(s):  
Yo Shinoda ◽  
Tetsushi Sadakata ◽  
Kazuhito Nakao ◽  
Ritsuko Katoh-Semba ◽  
Emi Kinameri ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Late Phase ◽  
Biological Significance ◽  
Long Term Potentiation ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Dense Core Vesicle ◽  
Calcium Dependent ◽  
Postsynaptic Currents ◽  
Activator Protein

Calcium-dependent activator protein for secretion 2 (CAPS2) is a dense-core vesicle-associated protein that is involved in the secretion of BDNF. BDNF has a pivotal role in neuronal survival and development, including the development of inhibitory neurons and their circuits. However, how CAPS2 affects BDNF secretion and its biological significance in inhibitory neurons are largely unknown. Here we reveal the role of CAPS2 in the regulated secretion of BDNF and show the effect of CAPS2 on the development of hippocampal GABAergic systems. We show that CAPS2 is colocalized with BDNF, both synaptically and extrasynaptically in axons of hippocampal neurons. Overexpression of exogenous CAPS2 in hippocampal neurons of CAPS2-KO mice enhanced depolarization-induced BDNF exocytosis events in terms of kinetics, frequency, and amplitude. We also show that in the CAPS2-KO hippocampus, BDNF secretion is reduced, and GABAergic systems are impaired, including a decreased number of GABAergic neurons and their synapses, a decreased number of synaptic vesicles in inhibitory synapses, and a reduced frequency and amplitude of miniature inhibitory postsynaptic currents. Conversely, excitatory neurons in the CAPS2-KO hippocampus were largely unaffected with respect to field excitatory postsynaptic potentials, miniature excitatory postsynaptic currents, and synapse number and morphology. Moreover, CAPS2-KO mice exhibited several GABA system-associated deficits, including reduced late-phase long-term potentiation at CA3–CA1 synapses, decreased hippocampal theta oscillation frequency, and increased anxiety-like behavior. Collectively, these results suggest that CAPS2 promotes activity-dependent BDNF secretion during the postnatal period that is critical for the development of hippocampal GABAergic networks.

scholarly journals Silencing-Induced Metaplasticity in Hippocampal Cultured Neurons

2008 ◽  
Vol 100 (2) ◽  
pp. 690-697 ◽  
Author(s):  
Irina V. Sokolova ◽  
Istvan Mody
Keyword(s):  
Hippocampal Neurons ◽  
Channel Blocker ◽  
Recovery Period ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Membrane Properties ◽  
Postsynaptic Currents ◽  
Short Period ◽  
Spiking Activity

Silencing-induced homeostatic plasticity is usually expressed as a change in the amplitude or the frequency of miniature postsynaptic currents. Here we report that, prolonged (∼24 h) silencing of mature (20–22 days in vitro) cultured hippocampal neurons using the voltage-gated sodium channel blocker tetrodotoxin (TTX) produced no effects on the amplitude or frequency of the miniature excitatory postsynaptic currents (mEPSCs). However, the silencing changed the intrinsic membrane properties of the neurons, resulting in an increased excitability and rate of action potentials firing upon TTX washout. Allowing neurons to recover in TTX-free recording solution for a short period of time after the silencing resulted in potentiation of mEPSC amplitudes. This form of activity-dependent potentiation is different from classical long-term potentiation, as similar potentiation was not seen in nonsilenced neurons treated with bicuculline to raise their spiking activity to the same level displayed by the silenced neurons during TTX washout. Also, the potentiation of mEPSC amplitudes after the recovery period was not affected by the N-methyl-d-aspartate receptor blocker d-2-amino-5-phosponopentanoic acid or by the calcium/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 but was abolished by the L-type calcium channel blocker nifedipine. We thus conclude that the potentiation of mEPSC amplitudes following brief recovery of spiking activity in chronically silenced neurons represents a novel form of metaplasticity that differs from the conventional models of homeostatic synaptic plasticity.

scholarly journals Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons

2020 ◽  
Author(s):  
Yu Wu ◽  
Xinyou Lv ◽  
Haiting Wang ◽  
Kai Qian ◽  
Jinjun Ding ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Late Phase ◽  
Adaptor Protein ◽  
Long Term Potentiation ◽  
Nuclear Accumulation ◽  
Transcriptional Responses ◽  
Axon Terminals ◽  
Term Potentiation

Abstract Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal plasticity. Here, we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1. Disrupting the interaction of APPL1 with Importin α1 abolishes nuclear accumulation of APPL1, which in turn decreases the levels of histone acetylation. We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation. Thus, these results illustrate an APPL1-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.

scholarly journals Calcium-dependent activator protein for secretion 2 interacts with the class II ARF small GTPases and regulates dense-core vesicle trafficking

FEBS Journal ◽  
2011 ◽  
Vol 279 (3) ◽  
pp. 384-394 ◽  
Author(s):  
Tetsushi Sadakata ◽  
Yukiko Sekine ◽  
Megumi Oka ◽  
Makoto Itakura ◽  
Masami Takahashi ◽  
...  
Keyword(s):  
Vesicle Trafficking ◽  
Class Ii ◽  
Small Gtpases ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Calcium Dependent ◽  
Activator Protein

2-Deoxyglucose–Induced Long-Term Potentiation of Monosynaptic IPSPs in CA1 Hippocampal Neurons

2000 ◽  
Vol 83 (2) ◽  
pp. 879-887 ◽  
Author(s):  
Krešimir Krnjević ◽  
Yong-Tao Zhao
Keyword(s):  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Current Clamp ◽  
Glutamate Antagonists ◽  
Postsynaptic Potentials ◽  
Postsynaptic Currents ◽  
Inhibitory Postsynaptic Potentials ◽  
Term Potentiation

In previous experiments on excitatory synaptic transmission in CA1, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) consistently caused a marked and very sustained potentiation (2-DG LTP). To find out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentials (IPSPs; under current clamp) and inhibitory postsynaptic currents (IPSCs; under voltage clamp); 2-DG was applied both in the presence and the absence of antagonists of N-methyl-d-aspartate (NMDA). In spite of sharply varied results (some neurons showing large potentiation, lasting for >1 h, and many little or none), overall there was a significant and similar potentiation of IPSP conductance, both for the early (at ≈30 ms) and later (at ≈140 ms) components of IPSPs or IPSCs: by 35.1 ± 10.25% (mean ± SE; for n = 24, P = 0.0023) and 36.5 ± 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPSP points to a presynaptic mechanism of LTP. Overall, the LTP was statistically significant only when 2-DG was applied in the absence of glutamate antagonists. Tetanic stimulations (in presence or absence of glutamate antagonists) only depressed IPSPs (by half). In conclusion, although smaller and more variable, 2-DG–induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG–induced LTP of excitatory postsynaptic potentials previously observed in CA1.

scholarly journals Implications of Extended Inhibitory Neuron Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes
Keyword(s):  
Neural Circuit ◽  
Inhibitory Neuron ◽  
Postnatal Period ◽  
Specific Pattern ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Neuron Development ◽  
Cortical Regions ◽  
Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

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