Intracellular Correlates of Spatial Memory Acquisition in Hippocampal Slices: Long-Term Disinhibition of CA1 Pyramidal Cells

2001 ◽  
Vol 86 (2) ◽  
pp. 881-899 ◽  
Author(s):  
Pavel A. Gusev ◽  
Daniel L. Alkon
Keyword(s):  
Dorsal Hippocampus ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Membrane Properties ◽  
Postsynaptic Potentials ◽  
Ca1 Pyramidal Cells ◽  
The Mean ◽  
Reversal Potentials

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and naı̈ve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.

Membrane properties and synaptic currents evoked in CA1 interneuron subtypes in rat hippocampal slices

1996 ◽  
Vol 76 (1) ◽  
pp. 1-16 ◽  
Author(s):  
F. Morin ◽  
C. Beaulieu ◽  
J. C. Lacaille
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Membrane Properties ◽  
Postsynaptic Potentials ◽  
Postsynaptic Currents ◽  
Current Pulses ◽  
Intrinsic Membrane Properties ◽  
Reversal Potentials

1. Intrinsic membrane properties and pharmacologically isolated excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) were characterized with the use of whole cell current- and voltage-clamp recordings, in combination with biocytin labeling, in different subtypes of CA1 interneurons and pyramidal cells in rat hippocampal slices. 2. Three classes of interneurons were selected on the basis of their soma location in the CA1 region: 1) in stratum (str.) oriens near the alveus (O/A), 2) near str. pyramidale, and 3) near the border of str. radiatum and lacunosum-moleculare. Each class of biocytin-labeled cells demonstrated specific cellular morphology. The somata of all interneurons were nonpyramidal in shape and usually multipolar. However, the pattern of dendritic and axonal arborizations of labeled interneurons differed in each class. 3. In current-clamp recordings, all interneuron subtypes had shorter-duration and smaller-amplitude action potentials than pyramidal cells. Fast- and medium-duration afterhyperpolarizations were larger in amplitude in interneurons. Cell input resistance was greater and membrane time constant was faster in all interneuron subtypes than in pyramidal cells. 4. Depolarizing current pulses evoked regular firing in all classes of interneurons, whereas burst firing was observed in 50% of pyramidal cells. With hyperpolarizing current pulses, all nonpyramidal and pyramidal cell types displayed inward rectification followed by anodal break excitation. 5. Electrical stimulation of nearby afferents evoked excitatory postsynaptic potentials (EPSPs) in all cells. EPSPs were of short duration and usually followed by inhibitory postsynaptic potentials (IPSPs). EPSPs were mediated by glutamate, because they were blocked by non-N-methyl-D-aspartate (non-NMDA) and NMDA antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-5-phosphonopentanoic acid (AP5), respectively]. In the presence of these antagonists, IPSPs were evoked in isolation and reversed near -72 mV. 6. In voltage-clamp recordings, non-NMDA EPSCs were isolated pharmacologically in the presence of AP5 and the gamma-aminobutyric acid-A (GABAA) antagonist bicuculline (BIC). Their properties were similar in all interneuron subtypes and pyramidal cells. Current-voltage (I-V) relations were linear, and mean reversal potentials were near 5 mV. Non-NMDA EPSCs were reversibly antagonized by CNQX. 7. NMDA EPSCs were pharmacologically isolated during CNQX and BIC application and were observed in all cell types. I-V relations of NMDA EPSCs demonstrated a region of negative slope at membrane potentials between -80 and -20 mV and their reversal potential was near 7 mV. The rise time of NMDA EPSCs was significantly slower in O/A interneurons than in other cell types. NMDA EPSCs were reversibly antagonized by AP5. 8. GABAA IPSCs were pharmacologically isolated in AP5 and CNQX and their properties were similar in all cell types. I-V relations of GABAA IPSCs were linear with mean reversal potentials near -32 mV. GABAA IPSCs were reversibly blocked by BIC. 9. In conclusion, morphologically different subtypes of interneurons located in O/A, near str. pyramidale, and near the str. radiatum/lacunosum-moleculare border displayed intrinsic membrane properties that were distinct from pyramidal cells, but were similar among them. In contrast, the properties of non-NMDA, NMDA, and GABAA postsynaptic currents were similar between interneurons and pyramidal cells, except for NMDA EPSCs, which had slower rise times in O/A interneurons.

scholarly journals PKMζ traces hippocampal LTP maintenance and spatial long-term memory

2020 ◽  
Author(s):  
Changchi Hsieh ◽  
Panayiotis Tsokas ◽  
Ain Chung ◽  
Claudia Garcia-Jou ◽  
Edith Lesburguères ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Hippocampal Formation ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Term Memory ◽  
Ca1 Pyramidal Cells

PKMζ is an autonomously active, atypical PKC isoform crucial for maintaining synaptic long-term potentiation (LTP) and long-term memory. Unlike other PKCs that are transiently activated by short-lived second messengers, PKMζ is persistently activated by long-lasting increases in the amount of the autonomously active kinase during LTP and long-term memory maintenance. Thus, localizing persistent increases in PKMζ might reveal traces of physiological LTP maintenance in the circuitry of the brain during long-term memory storage. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we visualized the amount and distribution of PKMζ during LTP maintenance and spatial long-term memory storage in the hippocampal formation of wild-type mice. Strong afferent stimulation of Schaffer collateral/commissural fibers inducing LTP maintenance increases PKMζ in CA1 pyramidal cells for 2 hours in hippocampal slices. Active place avoidance spatial conditioning increases PKMζ in CA1 pyramidal cells of the hippocampal formation from 1 day to at least 1 month. The increases in PKMζ coincide with the location of cells marked during long-term memory training by Arc promoter-mediated expression of a fluorescent protein, including at dendritic spines. We conclude that increased PKMζ forms persistent traces in CA1 pyramidal cells that are sites of molecular information storage during LTP maintenance and spatial long-term memory.Graphical AbstractPKMζ-immunohistochemistry reveals persistent increased PKMζ in the hippocampus during (A) LTP maintenance, and (B) spatial long-term memory storage.

scholarly journals Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation

1999 ◽  
Vol 81 (2) ◽  
pp. 781-787 ◽  
Author(s):  
Shao-Nian Yang ◽  
Yun-Gui Tang ◽  
Robert S. Zucker
Keyword(s):  
Calcium Concentration ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Biological Information ◽  
Synaptic Modulation ◽  
Ca1 Pyramidal Cells ◽  
Caged Calcium ◽  
Term Potentiation ◽  
Calcium Compound

Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation. Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.

Mechanisms of selective long-term potentiation of excitatory synapses in stratum oriens/alveus interneurons of rat hippocampal slices

1995 ◽  
Vol 73 (2) ◽  
pp. 810-819 ◽  
Author(s):  
M. Ouardouz ◽  
J. C. Lacaille
Keyword(s):  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Peak Amplitude ◽  
Excitatory Synapses ◽  
Metabotropic Glutamate ◽  
Stratum Oriens ◽  
Term Potentiation ◽  
The Mean

1. We investigated long-term potentiation (LTP) of synaptic transmission in different populations of interneurons in the CA1 region of rat hippocampal slices using whole cell recordings. We elicited excitatory postsynaptic currents (EPSCs) in interneurons located in stratum oriens near the alveus (O/A) or in stratum lacunosum-moleculare near the stratum radiatum border (L-M) by electrical stimulation of nearby axons in stratum oriens and radiatum, respectively. 2. High-frequency stimulation (100 Hz, 1 s) of axons in conjunction with postsynaptic depolarization (to -20 mV) increased the peak amplitude of test EPSCs elicited at -80 mV in O/A interneurons. The mean peak amplitude of EPSCs was significantly potentiated relative to the control period at 10 min (39 +/- 7% increase, mean +/- SE; n = 11 cells) and 30 min (30 +/- 1% increase; n = 5 cells) after tetanization. Similar stimulation did not produce potentiation of EPSCs in L-M interneurons (n = 7 cells). 3. This selective LTP in O/A interneurons was reversibly blocked by the N-methyl-D-aspartate receptor antagonist (+/-)2-amino-5-phosphonopentanoic acid (AP-5). Tetanization in the presence of 25 microM AP-5 did not increase the amplitude of EPSCs (8 cells). After washout of AP-5 (4 cells), a second tetanization resulted in long-term potentiation of EPSCs. 4. LTP was dependent on the activation of metabotropic glutamate receptors. The peak amplitude of EPSCs was not increased 5-10 or 15-20 min after tetanization during bath application of the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (500 microM) (n = 5 cells). 5. Inclusion of the Ca2+ chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA; 25 mM) in the patch pipette blocked LTP in O/A interneurons. In five cells recorded with BAPTA-containing electrodes, the mean peak amplitude was not significantly increased after tetanization. Thus a rise in postsynaptic intracellular Ca2+ appeared necessary for the induction of LTP in these interneurons. 6. Incubation of slices with the inhibitor of nitric oxide synthase N omega-nitro-L-arginine methyl ester (100 microM) before and throughout the recording session also blocked the increase in EPSC amplitude at 5-10 min (5 cells) and 15-20 min (3 cells) after tetanization. NO synthesis may therefore be necessary for LTP in O/A interneurons. 7. These results suggest that LTP of excitatory synapses is selectively produced in O/A but not L-M interneurons, and that this LTP shares similar characteristics with LTP in hippocampal CA1 pyramidal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices

1993 ◽  
Vol 69 (1) ◽  
pp. 219-229 ◽  
Author(s):  
G. Christofi ◽  
A. V. Nowicky ◽  
S. R. Bolsover ◽  
L. J. Bindman
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Receptor Subtypes ◽  
Postsynaptic Neuron ◽  
Conditioning Procedure ◽  
Long Term Depression ◽  
Postsynaptic Potentials ◽  
The Mean ◽  
Conditioning Stimuli

1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5–3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by antidromic stimulation, the mean EPSP slope was 52.6 +/- 11.4% (mean +/- SE) of its control at 30–35 min after conditioning (n = 7). The LTD produced by intracellular conditioning was of similar magnitude: the mean EPSP slope was 57.2 +/- 11.6% of its control at 30-35 min postconditioning (n = 7). When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+ without conditioning stimuli, there was no LTD (mean EPSP slope 109 +/- 8.1% of its control at 30–35 min after reperfusion with CSF; n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Long-term potentiation at single fiber inputs to hippocampal CA1 pyramidal cells.

1996 ◽  
Vol 93 (16) ◽  
pp. 8710-8715 ◽  
Author(s):  
J. T. Isaac ◽  
G. O. Hjelmstad ◽  
R. A. Nicoll ◽  
R. C. Malenka
Keyword(s):  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Single Fiber ◽  
Ca1 Pyramidal Cells ◽  
Term Potentiation ◽  
Hippocampal Ca1

Long-term potentiation in hippocampal slices induced by temporary suppression of glycolysis

1995 ◽  
Vol 74 (6) ◽  
pp. 2763-2766 ◽  
Author(s):  
S. Tekkok ◽  
K. Krnjevic
Keyword(s):  
Nmda Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Excitatory Postsynaptic Potentials ◽  
Postsynaptic Potentials ◽  
After Effects ◽  
Population Spikes ◽  
Term Potentiation

1. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG)-long enough to abolish CA1 population spikes (PSs) and reduce field excitatory postsynaptic potentials (EPSPs) by two-thirds-is followed by a sustained rebound of EPSPs and PSs (both up by 70-150%). 2. Post 2-DG long-term potentiation (2-DG-LTP) is prevented by block of N-methyl-D-aspartate (NMDA) receptors (NMDARs). Though 2-DG-LTP is normally expressed by other receptors, in presence of picrotoxin 2-DG causes similar LTP of NMDAR-mediated EPSPs. 3. Stimulation at 1 s-1 fully depotentiates 2-DG-LTP. 4. Unlike tetanic LTP, 2-DG-LTP is not pathway-specific, is not occluded by a preceding tetanic LTP (or vice versa) and is insensitive to block of NO synthesis. 5. Hypoglycemic states may have long-lasting after-effects on cerebral synaptic function.

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