AstroModulation · Astroglial control of axonal excitability, adaptation and analogue signalling

Astroglial control of axonal excitability, adaptation and analogue signalling

Neurons enjoy an elite status in biology as a diverse group of highly specialized cells responsible of high cognitive functions. Glial cells, by comparison, are still viewed by many as those sweeping the extracellular milieu free of excess potassium, neurotransmitter, and cellular debris, or wrapping axons with insulating lipid to facilitate conduction of nerve impulses. Only relatively recently, astrocytes in particular came into light as active contributors to signaling and information processing in the brain. Action potentials (APs) are usually considered as an elementary unit of information conveyed by presynaptic neurons to their postsynaptic target. Thus, neuronal signals in brain circuits are traditionally thought to occur in an all-or none, or digital, fashion. However, an increasing amount of studies indicates that subthreshold analogue variation in presynaptic membrane potential modulates spike-evoked transmission. One of the main proposed mechanisms involved in this process is the modification of the AP shape via the regulation of axonal potassium and sodium conductances. Our main hypothesis is that astrocytes engage their potassium channels and potassium-sodium exchange pumps, and probably release glutamate, to affect action potential shape and propagation speed in the nearby axons. Thus, local network activity sensed and integrated by individual astrocytes could modify presynaptic calcium entry and therefore synaptic efficacy. We aim to establish physiological mechanisms underlying this modification and the ensuing changes in short and long synaptic plasticity. Overall objectives are as follow: A) To establish through which molecular and cellular machinery the astrocyte activity controls axonal excitability and thus AP shape in the area they cover. B) To test whether modification of axonal signalling by the astrocyte plays a role in adaptation of the synaptic transmission, including short-term use-dependent efficacy changes. C) To establish whether modification of synaptic transmission by the astrocyte plays a role in long-term plasticity rules such as Spike-Timing Dependent Plasticity (STDP)

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