Clinically relevant concentrations of ketamine mainly affect long-term potentiation rather than basal excitatory synaptic transmission and do not change paired-pulse facilitation in mouse hippocampal slices

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

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Metabotropic glutamate receptor agonists induce long-term potentiation of synaptic transmission and enhance 2-deoxyglucose uptake and leucine incorporation In rat hippocampal slices.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)51984-9 ◽

1993 ◽

Vol 61 ◽

pp. 281

Author(s):

Yoshitsuau Minamoto ◽

Takeshi Tanaka ◽

Shigenobu Shibata ◽

Shigenori Watanabe

Keyword(s):

Synaptic Transmission ◽

Glutamate Receptor ◽

Metabotropic Glutamate Receptor ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Leucine Incorporation ◽

Metabotropic Glutamate ◽

Term Potentiation ◽

Glutamate Receptor Agonists

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Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice

Brain Research ◽

10.1016/s0006-8993(99)01698-4 ◽

1999 ◽

Vol 840 (1-2) ◽

pp. 23-35 ◽

Cited By ~ 174

Author(s):

John Larson ◽

Gary Lynch ◽

Dora Games ◽

Peter Seubert

Keyword(s):

Synaptic Transmission ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Term Potentiation

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Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus

Endocrinology ◽

10.1210/en.2003-0395 ◽

2003 ◽

Vol 144 (9) ◽

pp. 4195-4203 ◽

Cited By ~ 87

Author(s):

Li Sui ◽

M. E. Gilbert

Keyword(s):

Thyroid Hormone ◽

Synaptic Transmission ◽

Long Term Potentiation ◽

Synaptic Function ◽

Learning Deficits ◽

Paired Pulse ◽

Area Ca1 ◽

Term Potentiation ◽

Paired Pulse Depression

Abstract Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.

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Developmental increase in CA3-CA1 presynaptic function in the hippocampal slice

Journal of Neurophysiology ◽

10.1152/jn.1995.73.5.1821 ◽

1995 ◽

Vol 73 (5) ◽

pp. 1821-1828 ◽

Cited By ~ 36

Author(s):

T. C. Dumas ◽

T. C. Foster

Keyword(s):

Hippocampal Slices ◽

Age Groups ◽

Extracellular Recording ◽

Long Term Potentiation ◽

Developmental Differences ◽

Excitatory Postsynaptic Potential ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Presynaptic Function ◽

Term Potentiation

1. We recorded extracellular and intracellular CA3-CA1 synaptic responses in hippocampal slices from neonatal rats [postnatal day (P) 15-21 and P29-35]. Presynaptic function was examined by measuring input-output relationships and paired-pulse facilitation and by quantal analysis of minimally evoked responses. 2. Extracellular recording revealed no difference in excitatory postsynaptic potential (EPSP) threshold or the fiber potential response for a given stimulus intensity between the two age groups. However, the slope of the field EPSP was consistently larger in older animals. The increase in EPSP slope was associated with a decrease in paired-pulse facilitation, suggesting an increase in presynaptic function with postnatal development. 3. Extracellular results were confirmed by intracellular recordings that revealed no difference in the minimal stimulation intensity needed to evoke a response, an increase in mean EPSP amplitude with development, and a decrease in paired-pulse facilitation. Quantal parameters were extracted by three separate methods including method of failures, coefficient of variance, and parameter optimization through noise deconvolution. All methods supported presynaptic mediation of facilitation. Comparison of quantal parameters during development indicated an increase in mean quantal content. 4. The results demonstrate that synaptic strength is altered over the course of development because of, at least in part, changes in presynaptic release mechanisms. Developmental differences in presynaptic function provide an explanation of differences in mechanisms for expression of long-term potentiation. The lower initial probability of transmitter release in neonates may permit increased presynaptic change.

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