Disturbance of Membrane Function Preceding Ischemic Delayed Neuronal Death in the Gerbil Hippocampus

Slice preparations were made from the hippocampus of gerbils after 5 min of ischemia by carotid artery occlusion and the membrane properties of pyramidal neurons were examined. A majority of CA1 neurons lost the capacity for long-term potentiation following tetanic stimulation of the input fibers. CA3 pyramidal neurons, in contrast, preserved responses similar to those in the normal gerbil. Following ischemia, CA1 pyramidal neurons showed increased spontaneous firing that was highly voltage dependent and was blocked by intracellular injection of the Ca2+ chelator, EGTA. Thirty-five percent of CA1 neurons showed an abnormal slow oscillation of the membrane potential after 24 h following ischemia. Intracellular injection of GTPγS or IP3 produced facilitation of the oscillations followed by irreversible depolarization. Our results indicate that ischemia-damaged CA1 neurons suffer from abnormal Ca2+ homeostasis, involving IP3-induced liberation of Ca2+ from internal stores.

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Distinct LTP induction mechanisms: contribution of NMDA receptors and voltage-dependent calcium channels

Journal of Neurophysiology ◽

10.1152/jn.1995.73.1.270 ◽

1995 ◽

Vol 73 (1) ◽

pp. 270-279 ◽

Cited By ~ 74

Author(s):

K. M. Huber ◽

M. D. Mauk ◽

P. T. Kelly

Keyword(s):

Nmda Receptor ◽

Pyramidal Neurons ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Nmda Receptor Antagonist ◽

K Channel ◽

Combined Application ◽

Term Potentiation ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels

1. Our results indicate that there are two distinct components of long-term potentiation (LTP) induced by the K+ channel blocker tetraethylammonium chloride (TEA) at synapses of hippocampal CA1 pyramidal neurons. Preincubation of hippocampal slices in the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5 phosphonovalerate (D,L-APV, 50 microM), reduced the magnitude of TEA LTP. In addition, the L-type voltage-dependent Ca2+ channel (VDCC) antagonist nifedipine (10 microM) attenuated TEA LTP. Only the combined application of D,L-APV plus nifedipine blocked the induction of TEA LTP. 2. Occlusion experiments demonstrated that saturation of VDCC-dependent TEA LTP did not reduce or occlude NMDA-receptor-dependent TEA LTP. These results indicate that the mechanisms underlying VDCC and NMDA receptor components of TEA LTP are different and do not share a common saturable mechanism. 3. TEA LTP was strictly dependent on NMDA receptor activity in slices with CA3-CA1 connections severed (isolated CA1 slices). In contrast to results obtained in slices with intact CA3-CA1 connections, the NMDA receptor antagonists APV (50 microM) or MK-801 dizocilpine (10 microM) completely blocked TEA LTP in isolated CA1. Consistent with this observation, the properties of TEA LTP in isolated CA1 were very similar to other types of NMDA-receptor-dependent plasticity such as tetanus-induced LTP; TEA LTP required presynaptic stimulation, displayed pathway specificity, and was occluded by tetanus-induced LTP.(ABSTRACT TRUNCATED AT 250 WORDS)

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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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Mechanism of impairment of long-term potentiation by amyloid β is independent of NMDA receptors or voltage-dependent calcium channels in hippocampal CA1 pyramidal neurons

Neuroscience Letters ◽

10.1016/j.neulet.2005.08.024 ◽

2005 ◽

Vol 391 (1-2) ◽

pp. 1-6 ◽

Cited By ~ 31

Author(s):

Izumi Nomura ◽

Nobuo Kato ◽

Toru Kita ◽

Hajime Takechi

Keyword(s):

Calcium Channels ◽

Pyramidal Neurons ◽

Amyloid Β ◽

Long Term Potentiation ◽

Ca1 Pyramidal Neurons ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels

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Faculty Opinions recommendation of Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725702799.793521723 ◽

2016 ◽

Author(s):

Johannes Hell

Keyword(s):

Pyramidal Neurons ◽

Long Term Potentiation ◽

Hippocampal Pyramidal Neurons ◽

Term Potentiation

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High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

Scientific Reports ◽

10.1038/s41598-021-83008-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raul Loera-Valencia ◽

Erika Vazquez-Juarez ◽

Alberto Muñoz ◽

Gorka Gerenu ◽

Marta Gómez-Galán ◽

...

Keyword(s):

Pyramidal Neurons ◽

Memory Function ◽

Long Term Potentiation ◽

Synaptic Function ◽

Cholesterol Homeostasis ◽

Stratum Radiatum ◽

Actin Binding ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation

AbstractAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.

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Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons

Journal of Neurophysiology ◽

10.1152/jn.00526.2011 ◽

2012 ◽

Vol 107 (4) ◽

pp. 1058-1066 ◽

Cited By ~ 26

Author(s):

Peng Zhang ◽

John E. Lisman

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Synaptic Strength ◽

Ca1 Neurons ◽

Metabotropic Glutamate ◽

Group I ◽

Term Potentiation ◽

Activity Dependent

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

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Altered Short-Term Synaptic Plasticity in Mice Lacking the Metabotropic Glutamate Receptor mGlu7

The Scientific World JOURNAL ◽

10.1100/tsw.2002.146 ◽

2002 ◽

Vol 2 ◽

pp. 730-737 ◽

Cited By ~ 35

Author(s):

Trevor J. Bushell ◽

Gilles Sansig ◽

Valerie J. Collett ◽

Herman van der Putten ◽

Graham L. Collingridge

Keyword(s):

Synaptic Plasticity ◽

Molecular Mechanisms ◽

Pyramidal Neurons ◽

Metabotropic Glutamate Receptor ◽

Long Term Potentiation ◽

Short Term ◽

Metabotropic Glutamate ◽

Term Potentiation ◽

Commissural Pathway ◽

Frequency Facilitation

Eight subtypes of metabotropic glutamate (mGlu) receptors have been identified of which two, mGlu5 and mGlu7, are highly expressed at synapses made between CA3 and CA1 pyramidal neurons in the hippocampus. This input, the Schaffer collateral-commissural pathway, displays robust long-term potentiation (LTP), a process believed to utilise molecular mechanisms that are key processes involved in the synaptic basis of learning and memory. To investigate the possible function in LTP of mGlu7 receptors, a subtype for which no specific antagonists exist, we generated a mouse lacking this receptor, by homologous recombination. We found that LTP could be induced in mGlu7-/- mice and that once the potentiation had reached a stable level there was no difference in the magnitude of LTP between mGlu7-/- mice and their littermate controls. However, the initial decremental phase of LTP, known as short-term potentiation (STP), was greatly attenuated in the mGlu7-/- mouse. In addition, there was less frequency facilitation during, and less post-tetanic potentiation following, a high frequency train in the mGlu7-/- mouse. These results show that the absence of mGlu7 receptors results in alterations in short-term synaptic plasticity in the hippocampus.

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