A model of synaptic plasticity: activation of mGluR I induced long-term theta oscillations in medial septal diagonal band of rat brain slice.

This study aimed to establish a model of synaptic plasticity by the activation of metabotropic glutamate receptor (mGluR) I in rat medial septal diagonal band (MSDB). Electrophysiological experiment was performed to record the theta frequency oscillation activities in rat MSDB slices. The data were recorded and analyzed with Spike 2 (CED, Cambridge, UK). Application of aminocyclopentane-1, 3-dicarboxylic acid (ACPD) to MSDB slices produced theta frequency oscillations (4-12 Hz) which persisted for hours after ACPD washout, suggesting the existence of a form of synaptic plasticity in long-term oscillations (LTOs). Addition of NMDA receptor antagonist AP5 (50 µM) caused no significant change in area power. In contrast, AMPA/Kainate receptor antagonist NBQX administration partially reduced the area power. Infusion of ZD7288, a hyperpolarization-activated channel (Ih) inhibitor, caused additional reduction to control level. Comparable effects were also observed with administration of DHPG (3, 5-dihydroxyphenylglycine) which also elicited LTOs. mGluR I activation induced theta oscillation and this activity maintained hours after drug washout. Both AMPA and hyperpolarization-activated channel make an essential contribution to LTO. Our study herein established a model of synaptic plasticity.

In vitro hippocampal gamma oscillation power as an index of in vivo CA3 gamma oscillation strength and spatial reference memory.

Neuronal synchronisation at gamma frequencies (30-100 Hz) has been implicated in cognition and memory. Gamma oscillations can be studied in various in vitro models, but their in vivo validity and their relationship with reference memory remains to be proven. By using the natural variation of wild type C57bl/6J mice, we assessed the relationships between reference memory and gamma oscillations recorded in hippocampal area CA3 in vivo and in vitro. Local field potentials (LFPs) were recorded from area CA3 in behaviourally-characterised freely moving mice, after which hippocampal slices were prepared for recordings in vitro of spontaneous gamma oscillations and kainate-induced gamma oscillations in CA3. The gamma-band power of spontaneous oscillations in vitro correlated with that of CA3 LFP oscillations during inactive behavioural states. The gamma-band power of kainate-induced oscillations correlated with the activity-dependent increase in CA3 LFP gamma-band power in vivo. Kainate-induced gamma-band power correlated with Barnes circular platform performance and object location recognition, but not with object novelty recognition. Kainate-induced gamma-band power was larger in mice that recognised the aversive context, but did not correlate with passive avoidance delay. The correlations between behavioural and electrophysiological measures obtained from the same animals show that the gamma-generating capacity of the CA3 network in vitro is a useful index of in vivo gamma strength and supports an important role of CA3 gamma oscillations in spatial reference memory.

The developmental regulation of glutamate receptor-mediated calcium signaling in primary cultured rat hippocampal neurons.

We have studied the developmental changes of glutamate-induced calcium (Ca²âº) response in primary cultured hippocampal neurons at three different stages of cultures, 3, 7-8, and 14-16 days in vitro (DIV), using fura-2 single-cell digital micro-fluorimetry. We found that glutamate-induced Ca²âº signaling was altered during development, and that two different ionotropic glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), were differently involved in the modulation of calcium response at different stages of neuronal culture. In the stages of culture at 3 and 8 DIV, glutamate-induced Ca²âº influx was mostly because of AMPAR activation and subsequent opening of voltage-dependent calcium channels, as Ca²âº response can be largely reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by nifedipine. In the advanced culture (14-17 DIV), glutamate-induced Ca²âº response was less sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione and nifedipine. Furthermore, AMPA-induced Ca²âº response increased in a time-dependent manner during the cultures of 3-8 DIV and then reduced in the advanced culture of 14-17 DIV. NMDA-induced Ca²âº influx increased in a time-dependent manner, with a marked increase in the advanced culture (14-17 DIV). These results suggest that glutamate-induced Ca²âº signaling switched from AMPA-voltage-dependent calcium channel to NMDA-calcium signaling during development.

The effect of aging-associated impaired mitochondrial status on kainate-evoked hippocampal gamma oscillations.

Oscillations in hippocampal neuronal networks in the gamma frequency band have been implicated in various cognitive tasks and we showed previously that aging reduces the power of such oscillations. Here, using submerged hippocampal slices allowing simultaneous electrophysiological recordings and imaging, we studied the correlation between the kainate-evoked gamma oscillation and mitochondrial activity, as monitored by rhodamine 123. We show that the initiation of kainate-evoked gamma oscillations induces mitochondrial depolarization, indicating a metabolic response. Aging had an opposite effect on these parameters: while depressing the gamma oscillation strength, it increases mitochondrial depolarization. Also, in the aged neurons, kainate induced significantly larger Ca2+ signals. In younger slices, acute mitochondrial depolarization induced by low concentrations of mitochondrial protonophores strongly, but reversibly, inhibits gamma oscillations. These data indicating that the complex network activity required by the maintenance of gamma activity is susceptible to changes and modulations in mitochondrial status.

Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent.

Normal ageing-associated spatial memory impairment has been linked to subtle changes in the hippocampal network. Here we test whether the age-dependent reduction in gamma oscillations can be explained by the changes in intrinsic properties of hippocampal interneurons. Kainate-induced gamma oscillations, but not spontaneous gamma oscillations, were reduced in slices from aged mice. CA3 interneurons were recorded in slices from young and aged mice using Fura-2-filled pipettes. Passive membrane properties, firing properties, medium- and slow-afterhyperpolarisation amplitudes, basal [Ca(2+)](i) and firing-induced [Ca(2+)](i) transients were not different with ageing. Kainate caused a larger depolarisation and increase in [Ca(2+)](i) signal in aged interneurons than in young ones. In contrast to young interneurons, kainate increased the medium- and slow-afterhyperpolarisation and underlying [Ca(2+)](i) transient in aged interneurons. Modulating the slow-afterhyperpolarisation by modulating L-type calcium channels with BAY K 8644 and nimodipine suppressed and potentiated, respectively, kainate-induced gamma oscillations in young slices. The age-dependent and stimulation-dependent increase in basal [Ca(2+)](i), firing-induced [Ca(2+)](i) transient and associated afterhyperpolarisation may reduce interneuron excitability and contribute to an age-dependent impairment of hippocampal gamma oscillations.

Properties of gamma frequency oscillatory activity induced in hippocampal slices from the adult GAD67-GFP (Deltaneo) mouse.

The green fluorescent protein (GFP)-linked expression of protein in transgenic mice provides an ideal tool for the correlation of structure and function in the CNS. An important target of study is the role of GABAergic neurons in oscillatory activity in the hippocampus, and this would be facilitated with transgenic mice in which GFP is linked to the expression of GABA markers. One such mouse is the GAD67-GFP (Deltaneo), and here we compare the properties of kainate- and carbachol-induced oscillatory activity generated in CA3 of hippocampal slices from heterozygous GAD67-GFP (Deltaneo) mice and wild type litter mates. For both paradigms and in both mouse preparations oscillations were generated in the 20-30Hz range, and for the kainate-, but not the carbachol-induced oscillations, there was a small but significant difference in peak frequency of the oscillations between GAD67-GFP (Deltaneo) mice (28.4+/-2.2Hz) and wild type mice (25+/-1.6Hz). For both oscillatory paradigms there was no significant difference between mouse strains in area power of the oscillatory activity in the stratum oriens lamina of CA3, but for the kainate-induced oscillations, area power became significantly diminished in the stratum radiatum lamina of the GAD67-GFP (Deltaneo) mouse compared with the wild type mouse after prolonged exposure to kainate. This gradual reduction in area power in CA3 of the transgenic mouse was rescued by inclusion of Guvacine, a GABA uptake inhibitor, suggesting that the reported lower levels of GABA in the GAD67-GFP (Deltaneo) mouse brain during development and in the adult may contribute to a reduction in the efficiency of GABA neurotransmission after prolonged stimulation of the GABAergic circuitry.