Developmental increase of asynchronic glutamate release from hippocampal synapses in mutant taiep rat

Abstract

During development, regulation of the strength of synaptic transmission plays a central role in the formation of mammalian brain circuitries. In taiep rat, a neurological mutant with severe reactive astrogliosis and demyelination, we have described alterations in the synaptic transmission in central neurons, characterized by asynchronous excitatory postsynaptic currents ((ASYN)EPSCs), because of delayed neurotransmitter release. This hippocampal synaptic dysfunction has been described in juvenile mutants, concomitantly with the appearance of their main glial alterations. However, it is unknown whether this abnormal synaptic activity is correlated with some alterations of synaptic maturation during the postnatal development. Using intracellular electrophysiological recordings and immunohistochemistry assays, we studied the maturation of CA3-CA1 synapses in taiep rats. In taiep, the number of (ASYN)EPSCs evoked by conventional stimulation of Schaffer collaterals increases with age (P7-P30) and can be evoked by stimulation of single fiber. The amplitude and frequency of spontaneous EPSC (sEPSC) increased during the postnatal development in both control and taiep rats. However, in taiep, the increase of sEPSC frequency was significantly higher than in the control rats. The frequency of miniature EPSC (mEPSC) increased over the studied age range, without differences between taiep and control rats. In both control and taiep groups, the synaptophysin immunostaining (SYP-IR) in the stratum radiatum of CA1 region was significantly lower in the juvenile (P30) than in the neonatal (P10) rats, suggesting that synaptic pruning is normally occurring in taiep, even when SYP-IR was higher in taiep than control in both ages studied. These results suggest that, in taiep mutants, the asynchronic transmission is due to a dysfunction in the glutamate release mechanisms that progressively increases during development, which is not attributable to the existence of aberrant synaptic contacts. Synapse 63:502-509, 2009. (c) 2009 Wiley-Liss, Inc.

Enhanced astroglial Ca2+ signaling increases excitatory synaptic strength in the epileptic brain

“…Acute hippocampal slices were obtained from control and kindled rats as previously described (Bonansco et al, ; Fuenzalida et al, ). Briefly put, the brain was rapidly removed and placed in ice‐cold artificial cerebrospinal fluid (ACSF) at 4 °C, and gassed with a mixture of 95% O 2 and 5% CO 2 (pH 7.4).…”

“…Only events with amplitudes higher than 5.0 pA, an exponential decay and a monotonic rising‐phase were considered mEPSCs. To compare the synaptic connectivity in kindled and control rats, the multiplicity index (MI), whose values indicate changes in the number of synaptic contacts between CA3‐CA1 neurons, was calculated (Fuenzalida et al, ; Hsia et al, ). Briefly, the amplitude and frequency mean values of sEPSC and mEPSC were obtained, recorded respectively before and after adding TTX.…”

Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity

“…The brain slices were obtained as previously described (Bonansco et al. , 2002, 2007; Fuenzalida et al. , 2007, 2009).…”

“…The procedures of animal care, surgery and slice preparation were in accordance with the guidelines laid down by the Institutional Animal Care and Ethics Committee at the Faculty of Sciences, Universidad de Valparaíso and NIH, USA. The brain slices were obtained as previously described (Bonansco et al, 2002(Bonansco et al, , 2007Fuenzalida et al, 2007Fuenzalida et al, , 2009). Coronal hippocampal slices were obtained from Sprague Dawley rats (60 animals; 25-35 days old) after they were anaesthetized with ether and decapitated immediately after the pinch reflex disappeared.…”

The nestin-expressing and non-expressing neurons in rat basal forebrain display different electrophysiological properties and project to hippocampus

“…To compare the synaptic connectivity, we calculated multiplicity index, a common parameter used as a maturation index in synaptic developmental studies, defined as the number of release sites per presynaptic neuron could release neurotransmitter simultaneously onto the recorded cell [ 35 - 37 ]. Multiplicity index was calculated as the mean amplitude of action-potential-driven events divided by mean quantal size (q: mean amplitude of mEPSCs).…”