Abstract
Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs). We here investigated whether interfering with connexin43 (Cx43) HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19) into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.
Highlights
Over the few last years, evidence has accumulated pointing to a key role for connexin43 (Cx43) signaling in neurophysiology (Cheung et al, 2014)
Our results demonstrate that inhibition of Cx43 HCs with TAT-Gap19 impaired spatial short-term memory without affecting locomotor activity or spatial working memory
We first determined whether i.c.v. administered compounds could reliably affect working memory as measured with our Y maze protocol
Summary
Over the few last years, evidence has accumulated pointing to a key role for connexin (Cx43) signaling in neurophysiology (Cheung et al, 2014). This work suggested that astrocytic Cx43 HC opening, gliotransmitter release and modulation of synaptic signaling might be operational under physiological conditions In line with this idea, it has been shown that astroglial Cx43 HCs can open under resting conditions and modulate basal synaptic transmission through ATP (Chever et al, 2014a) and glutamate (Chever et al, 2014b) signaling and that deletion of astroglial Cxs alters synaptic transmission and plasticity (Pannasch and Rouach, 2013). Fear learning capacity was recovered after co-infusing a cocktail of gliotransmitters (glutamate, D-serine, glutamine, ATP, lactate and glycine). These experiments substantiate a critical role for in vivo gliotransmission mediated by Cx43 HCs in fear memory. It is known that changes in neuronal plasticity, a substrate for memory (e.g., long-term potentiation), can be modulated by astrocytic gliotransmitter release (Ben Achour and Pascual, 2010; Moraga-Amaro et al, 2014)
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