Amplitude Of Field Excitatory Postsynaptic Potentials Research Articles

Calcium-permeable AMPA receptors are essential to the synaptic plasticity induced by epileptiform activity in rat hippocampal slices

Abnormal neuronal activity during epileptic seizures alters the properties of synaptic plasticity, and, consequently, leads to cognitive impairment. The molecular mechanism of these alterations in synaptic plasticity is still unclear. In the present study, using a 4-aminopyridine (4-AP) in vitro model, we demonstrated that epileptiform activity in rat hippocampal slices initially causes substantial enhancement of field excitatory postsynaptic potential amplitude. However, the potentiation of CA3-CA1 synapses was temporary and switched to long-term depression (LTD) within an hour. Previous studies showed that transient incorporation of calcium-permeable AMPA receptors (CP-AMPARs) is crucial for the consolidation of long-term potentiation (LTP). We confirmed that, in normal conditions, the blockage of CP-AMPARs prevented the consolidation of LTP induced by theta-burst stimulation (TBS). In contrast, the blockage of CP-AMPARs preserved synaptic potentiation induced by epileptiform activity. One hour after a period of epileptiform activity in the hippocampal slices, synaptic plasticity was substantially altered, and the TBS protocol was unable to produce LTP. Moreover, if CP-AMPARs were blocked, the TBS protocol induced LTD. Our results indicate that CP-AMPARs play an essential role in the molecular mechanism of the disturbances of synaptic plasticity caused by epileptiform activity.

Activation of β-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that β-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of β-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of β-adrenoceptor) and isoproterenol (an agonist of β-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of β-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of β-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

Radix Angelica Sinensis Promotes Synaptic Plasticity During Cognitive Recovery in Chronically Stressed Rats.

The accumulation of chronic stress is associated with cognitive dysfunction. Radix Angelica Sinensis (RAS) has been shown to have neuroprotective potential for treating Alzheimer's disease and vascular dementia. However, the impact of RAS on cognitive impairment induced by chronic stress has not been studied. In the present study, RAS significantly alleviated cognitive deficits in rats subjected to chronic restraint stress. This neuroprotective effect was associated with enhancement of synaptic efficacy by improving field excitatory postsynaptic potential amplitudes, alleviating adverse alterations in the structure of synapses and neurons in the hippocampus, and increasing the levels of brain-derived neurotrophic factor, microtubule-associated protein-2, and synaptophysin in the hippocampus. These findings provide initial evidence for the therapeutic potential of RAS for the treatment of neuronal deterioration caused by chronic stress.

Neprilysin-sensitive Synapse-associated Amyloid-β Peptide Oligomers Impair Neuronal Plasticity and Cognitive Function

Neprilysin-sensitive Synapse-associated Amyloid-β Peptide Oligomers Impair Neuronal Plasticity and Cognitive Function

Plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex in the rat in vivo: paired-pulse facilitation, long-term potentiation and short-term depression

Several neurophysiological and computational theories of the rodent navigational system suggest that the differing cortices of the frontal lobe and thalamus share information and therefore undergo changes in synaptic strength. We examine here for the first time three forms of synaptic plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex: we demonstrate that this projection is capable of expressing paired-pulse facilitation, long-term potentiation, and short-term depression. Furthermore, input/output curves show that field excitatory post-synaptic potential amplitude increased at all stimulus intensities following high-frequency stimulation. These findings add important information to our understanding of synaptic plasticity in this important pathway, which has been widely hypothesized to play important roles in memory and spatial representation in the rodent.

Kainate receptor-mediated inhibition of presynaptic Ca2+ influx and EPSP in area CA1 of the rat hippocampus.

1. The effect of a low concentration (1 microM) of kainate (kainic acid; KA) on presynaptic calcium (Ca2+) influx at the Schaffer collateral-commissural (SCC) synapse was examined in rat hippocampal slices. 2. Following selective loading of the presynaptic terminals with the fluorescent Ca2+ indicator rhod-2 AM, transient increases in the presynaptic Ca2+ concentration (pre[Ca2+]t) and field excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the SCC pathway were recorded simultaneously. 3. Bath application of 1 microM KA reversibly suppressed field EPSPs and pre[Ca2+]t to 37.7 +/- 4.0 % and 72.9 +/- 2.4 % of control, respectively. Excitatory postsynaptic currents (EPSCs) recorded with the use of the whole-cell patch-clamp technique were also suppressed by 1 microM KA to 42.6 +/- 6.3 % of control. A quantitative analysis of the decreases in pre[Ca2+]t and the amplitude of field EPSP during KA application suggests that KA inhibits transmission primarily by reducing the pre[Ca2+]t. 4. Consistent with a presynaptic site for these effects, paired-pulse facilitation (PPF) was enhanced by 1 microM KA. 5. A substantial KA-induced suppression of NMDA receptor-mediated EPSPs was detected when AMPA receptors were blocked by the AMPA receptor-selective antagonist GYKI 52466 (100 microM). 6. The suppressive effect of KA on field EPSPs and pre[Ca2+]t was antagonized by the KA antagonist NS-102 (10 microM). 7. These results suggest that the presynaptic inhibitory action of KA at the hippocampal CA1 synapse is primarily due to the inhibition of Ca2+ influx into the presynaptic terminals.

The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats.

In some central systems, excitatory postsynaptic potential (EPSP) amplitude increases substantially during repetitive synaptic stimulation ("frequency potentiation"), as does the probability of spike generation. An apparently analogous phenomenon at the neuromuscular junction ("frequency facilitation") depends on residual Ca2+ in nerve terminals. However, the mechanisms of central frequency potentiation are not completely defined and it is therefore not clear whether the patterns of Ca2+-dependent synaptic plasticity are fully analogous in central and peripheral systems. In addition, an age-related deficit in hippocampal frequency potentiation has been previously described, and the degree of sensitivity of this deficit to Mg2+-to-Ca2+ balance could yield important insights into its nature. In these studies, we used the hippocampal slice preparation to examine the effects of varying Mg2+-to-Ca2+ ratios in the artificial cerebrospinal fluid (ACF) on frequency potentiation in aged and young rats. Extracellular and intracellular methods were used to assess the responses of hippocampal CA1 neurons during orthodromic stimulation of the monosynaptic Schaffer-commissural pathway. In experiment 1, frequency potentiation of the hippocampal population spike during 7-Hz stimulation was found to be significantly greater in an ACF with a high Mg2+-to-Ca2+ ratio (2.7) than in an ACF with a normal Mg2+-to-Ca2+ ratio (0.5), for both young and aged rat slices. Aged slices exhibited less frequency potentiation than young in both media. In experiment 2, the field EPSP and population spike were monitored concurrently, and the differences in Mg2+-to-Ca2+ ratio between the high Mg2+-to-Ca2+ ACF ratio (2.0) and normal Mg2+-to-Ca2+ ACF ratio (1.0) were reduced, to determine whether aged and young brains differed in sensitivity to smaller variations in Mg2+-to-Ca2+ balance. Under these conditions, the effects of high Mg2+-to-Ca2+ ratios on frequency potentiation (at 7 Hz) were found to be most pronounced in aged rat slices, particularly for potentiation of the spike. No effects were seen of age or Mg2+-to-Ca2+ ratios on presynaptic fiber volley amplitudes. Field EPSP (but not spike) amplitudes were reduced with aging, in an input-output (I/O) stimulation series at control frequency (0.2 Hz). However, the high Mg2+-to-Ca2+ ACF ratio of (2.0), which improved field EPSP frequency potentiation, did not decrease control field EPSP amplitudes in the I/O series. Therefore, the effects of high MG2+-to-Ca2+ ACF ratio on brain frequency potentiation seem to be mediated in part by mechanisms other than the classical reduction of release probability.(ABSTRACT TRUNCATED AT 400 WORDS)

BILIRUBIN REVERSIBLY REDUCES SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES

Bilirubin increases latencies and reduces amplitudes in the auditory brainstem response (ABR). However, the basic mechanisms involved are not known. The aim of the present study was to investigate the neurotoxic effects of bilirubin on synaptic transmission in an in vitro system. Hippocampal slices were prepared from 5-7 weeks old male Sprague-Dawley rats and incubated at 30-33°C in an artificial cerebrospinal fluid equilibrated with 95% O2 and 5% CO2 to pH 7.4. We stimulated the Schaffer collaterals of the CA3 cells. Recordings were made of the amplitudes of the presynaptic fibre volley (PV) and the field excitatory postsynaptic potential (EPSP) in the apical dendritic layer of the CA1 region, and of the population spike (PS) in the corresponding cell body layer. The slices were exposed to bilirubin at concentrations up to 1mM, in an 8:1 molar ratio with bovine serum albumin (BSA). Over periods of 30-120 minutes a gradual reduction in the field EPSP amplitude was noted. In parallel with this the peak latency of the PS increased. The stimulus/response relationships were examined with stimulus voltage from 1.0 to 3.4V. Bilirubin caused the PV/EPSP curve to shift to the right, while the EPSP/PS curve shifted to the left. These changes were reversed when bilirubin was removed from the perfusion fluid. The effect of bilirubin on rat hippocampal slices consists of a gradual and reversible decrease in synaptic transmission. This is consistent with the findings reported from ABR studies.