Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy

Abstract

Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established. In rat hypothalamic paraventricular nucleus, we demonstrate an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine that requires the release of ATP from glial cells. The increase in quantal efficacy, which likely results from an insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors, an increase in postsynaptic calcium and the activation of phosphatidylinositol 3-kinase. The gliotransmitter ATP, therefore, contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.

Connexin 30 controls the extension of astrocytic processes into the synaptic cleft through an unconventional non-channel function

“…The physiological relevance of the astrocyte plasticity identifi ed here is not well understood, but the authors suggest that it might contribute to the maturation of efficient synaptic strength during the postnatal development of the brain and basic cognitive functions in the adult brain by controlling the access of astrocytic processes to synaptic glutamate. It is noteworthy that similar changes in the glial coverage of synapses were previously observed in the hypothalamus, contributing to the regulation of several key processes such as lactation [9] , osmoregulation [10] , reproductive function [11] and more recently, feeding behavior [12] . Since astroglial …”

Two Forms of Astrocyte Calcium Excitability Have Distinct Effects on NMDA Receptor-Mediated Slow Inward Currents in Pyramidal Neurons

“…2) (12/12 cells). To further explore the hypothesis that the PAR-1 receptorevoked SICs are of astrocyte origin, we used fluoroacetate (FA; slices were pretreated with 10 M FA for 2 h) to selectively impair astrocyte function in brain slices (Fonnum et al, 1997;Gordon et al, 2005) and BAPTA-AM (Liu et al, 2004) to chelate astrocyte intracellular calcium (200 M BAPTA-AM for 1.5 h followed by 30 min at room temperature). We loaded Fluo-4 AM together with BAPTA-AM, as well as into slices treated with FA, to verify that the [Ca 2ϩ ] i transients were abolished in astrocytes.…”

Brief Bursts of Parallel Fiber Activity Trigger Calcium Signals in Bergmann Glia

“…Studies in the hippocampus, retina, thalamus, and other areas suggest that the most likely candidates for a transmitter released from astrocytes are glutamate and ATP (Kang et al, 1998;Guthrie et al, 1999;Parri et al, 2001;Newman, 2003;Angulo et al, 2004;Gordon et al, 2005). Release of these transmitters appears to be driven by calciumdependent vesicle-mediated exocytosis, although other mechanisms have been postulated (Evanko et al, 2004).…”

“…Studies performed at the neuromuscular junction (Robitaille, 1998), the retina (Newman and Volterra, 2004), the hippocampus (Kang et al, 1998;Pascual et al, 2005), and hypothalamus (Gordon et al, 2005) suggest that transmitter release from glia can also modulate ongoing synaptic transmission by acting on presynaptic receptors. Here, we tested this idea for BGs, by monitoring presynaptic calcium influx at PFs before and after brief PF bursts that trigger calcium signals in BGs.…”