The impact of astroglial dysfunction on excitatory synaptic transmission in neuropathological conditions: the epileptic hippocampus
Fecha
2015-08
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Universidad de Valparaíso
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Facultad de Ciencias
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Instituto de Neurociencia
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Doctor en Ciencias con Mención en Neurociencia
Resumen
Astroglial cells are essential components of brain machinery. Indeed, astrocytes modulate
synaptic transmission, neuronal excitability and plasticity in healthy brain, through the Ca2+-
dependent release of neuroactive substances, process referred to as gliotransmision.
Despite that altered astroglial physiology has been observed in several neuropathological
conditions including epilepsy, whether the astroglial Ca2+-dependent modulation of synaptic
transmission is also altered in such pathologies remains poorly understood. By using a
chronic model of epilepsy, the kindling, we investigated how astroglial physiology is affected
by the epileptogenesis induction, and what is the functional impact of altered astroglial
physiology on neuronal transmission. Because spontaneous astroglial Ca2+-mediated
glutamate gliotransmission is believed to modulate the hippocampal excitatory synaptic
efficacy, spontaneous astroglial Ca2+ elevations as well as CA3-CA1 synapses
electrophysiological properties were recorded from control and epileptic rats. Astrocytes from
epileptic slices display slow spontaneous Ca2+ transients and higher frequency of glutamate
gliotransmission -evaluated the astrocyte-dependent slow inward currents (SICs) recorded
form CA1 neurons- than control slices. CA1 SC-evoked, spontaneous and miniature
excitatory postsynaptic currents (eEPSC, sEPSC and mEPSC respectively) from epileptic
slices showed an increased synaptic efficacy compare to control slices. The increased
mEPSC frequency with no changes in mEPSC amplitude, the lowered pair-pulse facilitation
index (PPF) and the increased number of successful responses evoked by minimal
stimulation (meEPSC) obtained in epileptic slices suggest that the elevated excitatory
synaptic efficacy was mainly mediated by an increase in the probability of neurotransmitter
release (Pr). Remarkably, when astroglial Ca2+ signal were blocked by the intracellular
dialysis of BAPTA, there was a strong decrease on the synaptic efficacy of CA3-CA1
synapses from epileptic slices down to control values. P2Y purinergic receptors and group I glutamatergic metabotropic receptors (mGluR) antagonists also produced a decrease of the
Pr. Specifically, the data suggests that P2Y1R are involved in the astroglial Ca2+-signal
required for gliotransmission; and mGluR5 presynaptic receptors directly modulate
neurotransmitter release. These findings showed that astroglial Ca2+-signaling is increased
in the epileptic tissue strongly impacting synaptic function, which likely contribute to the
pathophysiology of epilepsy.
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ASTROCITOS, CELULAS ASTROGLIALES, NEUROLOGIA