Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aβ) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aβ on astroglial and neuronal network function remains unknown.Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aβ on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aβ density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aβ, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hyporesponsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.

We characterized the ionic currents underlying the cellular excitability and the Ca 2+ -channel subtypes involved in action potential (AP) firing of rat adrenal chromaffin cells (RCCs) preserved in their natural environment, the adrenal gland slices, through the perforated patch-clamp recording technique. RCCs prepared from adrenal slices exhibit a resting potential of À54 mV, firing spontaneous APs (2-3 spikes/s) generated by the opening of Na + and Ca 2+ -channels, and terminated by the activation of voltage and Ca-channels is involved in reaching threshold potential for AP firing, and is responsible for activation of BK-channels contributing to APrepolarization and afterhyperpolarization, whereas P/Q-type Ca 2+ -channels are involved only in the repolarization phase. BK-channels carry total outward current during AP-repolarization. Blockade of L-type Ca 2+ -channels reduces BK-current 60%, whereas blockade of N-or P/Q-type produces little effect. This study demonstrates that Ca 2+ influx through L-type Ca 2+ -channels plays a key role in modulating the threshold potential from RCCs in situ.

It is currently known that in CNS the extracellular matrix is involved in synaptic stabilization and limitation of synaptic plasticity. However, it has been reported that the treatment with chondroitinase following injury allows the formation of new synapses and increased plasticity and functional recovery. So, we hypothesize that some components of extracellular matrix may modulate synaptic transmission. To test this hypothesis we evaluated the effects of chondroitin sulphate (CS) on excitatory synaptic transmission, cellular excitability, and neuronal plasticity using extracellular recordings in the CA1 area of rat hippocampal slices. CS caused a reversible depression of evoked field excitatory postsynaptic potentials in a concentration-dependent manner. CS also reduced the population spike amplitude evoked after orthodromic stimulation but not when the population spikes were antidromically evoked; in this last case a potentiation was observed. CS also enhanced paired-pulse facilitation and long-term potentiation. Our study provides evidence that CS, a major component of the brain perineuronal net and extracellular matrix, has a function beyond the structural one, namely, the modulation of synaptic transmission and neuronal plasticity in the hippocampus.