Postsynaptic Expression of a New Calcium Pathway in Hippocampal CA3 Neurons and Its Influence on Mossy Fiber Long-Term Potentiation

The excitatory synaptic response evoked by stimulating the mossy fiber synaptic input to hippocampal CA3 neurons in normally accompanied by concomitant feedforward or recurrent inhibition. The purpose of the present study was to determine whether a decrease in the inhibitory conductance of this mixed synaptic response contributes to the enhanced synaptic efficacy observed during long-term potentiation (LTP). Intracellular recordings were made from CA3 neurons of rat hippocampal brain slices. Current- and voltage-clamp measurements of the mixed excitatory/inhibitory evoked synaptic response were made, using a single-electrode clamp system. Outward and inward rectification were reduced, respectively, by intracellular injection and bath application of Cs+. Biophysical analysis of the evoked synaptic conductance sequence was performed before and 15 min to 1 h after inducing LTP. As expected, measurements made in the early part of the conductance sequence, which represents primarily the monosynaptic excitatory input, demonstrated an increase in the slope conductance during LTP. Measurements made later in the conductance sequence, when the excitatory component appeared to have declined to a negligible value, revealed no decrease in the slope conductance of the inhibitory component of the mixed response. We conclude that a decrease in the conductance associated with the inhibitory component of the mixed synaptic response plays little or no role in the increase in synaptic efficacy observed during LTP of this synaptic system.

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Ultrastructure of light-activated axons following optogenetic stimulation to produce late-phase long-term potentiation

10.1101/799890 ◽

2019 ◽

Author(s):

Masaaki Kuwajima ◽

Olga I. Ostrovskaya ◽

Guan Cao ◽

Seth A. Weisberg ◽

Kristen M. Harris ◽

...

Keyword(s):

Late Phase ◽

Long Term Potentiation ◽

State Dependent ◽

Term Potentiation ◽

Section Electron ◽

Hippocampal Ca3 ◽

Ultrastructure And Function ◽

Ca3 Neurons ◽

And Function

AbstractAnalysis of neuronal compartments has revealed many state-dependent changes in geometry but establishing synapse-specific mechanisms at the nanoscale has proven elusive. We co-expressed channelrhodopsin2-GFP and mAPEX2 in a subset of hippocampal CA3 neurons and used trains of light to induce late-phase long-term potentiation (L-LTP) in area CA1. L-LTP was shown to be specific to the labeled axons by severing CA3 inputs, which prevented back-propagating recruitment of unlabeled axons. Membrane-associated mAPEX2 tolerated microwave-enhanced chemical fixation and drove tyramide signal amplification to deposit Alexa Fluor dyes in the light-activated axons. Subsequent post-embedding immunogold labeling resulted in outstanding ultrastructure and clear distinctions between labeled (activated), and unlabeled axons without obscuring subcellular organelles. The gold-labeled axons in potentiated slices were reconstructed through serial section electron microscopy; presynaptic vesicles and other constituents could be quantified unambiguously. The genetic specification, reliable physiology, and compatibility with established methods for ultrastructural preservation make this an ideal approach to link synapse ultrastructure and function in intact circuits.

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Photolysis of Postsynaptic Caged Ca2+ Can Potentiate and Depress Mossy Fiber Synaptic Responses in Rat Hippocampal CA3 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.01073.2003 ◽

2004 ◽

Vol 91 (4) ◽

pp. 1596-1607 ◽

Cited By ~ 17

Author(s):

Jun Wang ◽

Mark F. Yeckel ◽

Daniel Johnston ◽

Robert S. Zucker

Keyword(s):

Tyrosine Kinases ◽

Pyramidal Neurons ◽

Mossy Fiber ◽

Long Term Potentiation ◽

Ca1 Neurons ◽

Term Potentiation ◽

Hippocampal Ca3 ◽

Ca3 Pyramidal Neurons ◽

Cell Somata

The induction of mossy fiber-CA3 long-term potentiation (LTP) and depression (LTD) has been variously described as being dependent on either pre- or postsynaptic factors. Some of the postsynaptic factors for LTP induction include ephrin-B receptor tyrosine kinases and a rise in postsynaptic Ca2+ ([Ca2+]i). Ca2+ is also believed to be involved in the induction of the various forms of LTD at this synapse. We used photolysis of caged Ca2+ compounds to test whether a postsynaptic rise in [Ca2+]i is sufficient to induce changes in synaptic transmission at mossy fiber synapses onto rat hippocampal CA3 pyramidal neurons. We were able to elevate postsynaptic [Ca2+]i to approximately 1 μm for a few seconds in pyramidal cell somata and dendrites. We estimate that CA3 pyramidal neurons have approximately fivefold greater endogenous Ca2+ buffer capacity than CA1 neurons, limiting the rise in [Ca2+]i achievable by photolysis. This [Ca2+]i rise induced either a potentiation or a depression at mossy fiber synapses in different preparations. Neither the potentiation nor the depression was accompanied by consistent changes in paired-pulse facilitation, suggesting that these forms of plasticity may be distinct from synaptically induced LTP and LTD at this synapse. Our results are consistent with a postsynaptic locus for the induction of at least some forms of synaptic plasticity at mossy fiber synapses.

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Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system.

The Journal of Cell Biology ◽

10.1083/jcb.131.6.1789 ◽

1995 ◽

Vol 131 (6) ◽

pp. 1789-1800 ◽

Cited By ~ 101

Author(s):

Y Takei ◽

A Harada ◽

S Takeda ◽

K Kobayashi ◽

S Terada ◽

...

Keyword(s):

Mossy Fiber ◽

Long Term Potentiation ◽

Synapsin I ◽

Term Potentiation ◽

Gene Mutant ◽

Associated Proteins ◽

Hippocampal Ca3

Synapsin I is one of the major synaptic vesicle-associated proteins. Previous experiments implicated its crucial role in synaptogenesis and transmitter release. To better define the role of synapsin I in vivo, we used gene targeting to disrupt the murine synapsin I gene. Mutant mice lacking synapsin I appeared to develop normally and did not have gross anatomical abnormalities. However, when we examined the presynaptic structure of the hippocampal CA3 field in detail, we found that the sizes of mossy fiber giant terminals were significantly smaller, the number of synaptic vesicles became reduced, and the presynaptic structures altered, although the mossy fiber long-term potentiation remained intact. These results suggest significant contribution of synapsin I to the formation and maintenance of the presynaptic structure.

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