Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice

Pannexin 1 (Panx1) is an ubiquitously expressed protein that forms plasma membrane channels permeable to anions and moderate-sized signaling molecules (e.g., ATP, glutamate). In the nervous system, activation of Panx1 channels has been extensively shown to contribute to distinct neurological disorders (epilepsy, chronic pain, migraine, neuroAIDS, etc.), but knowledge of the extent to which these channels have a physiological role remains restricted to three studies supporting their involvement in hippocampus dependent learning. Given that Panx1 channels may provide an important mechanism for activity-dependent neuron-glia interaction, we used Panx1 transgenic mice with global and cell-type specific deletions of Panx1 to interrogate their participation in working and reference memory. Using the eight-arm radial maze, we show that long-term spatial reference memory, but not spatial working memory, is deficient in Panx1-null mice and that both astrocyte and neuronal Panx1 contribute to the consolidation of long-term spatial memory. Field potential recordings in hippocampal slices of Panx1-null mice revealed an attenuation of both long-term potentiation (LTP) of synaptic strength and long-term depression (LTD) at Schaffer collateral-CA1 synapses without alterations of basal synaptic transmission or pre-synaptic paired-pulse facilitation. Our results implicate both neuronal and astrocyte Panx1 channels as critical players for the development and maintenance of long-term spatial reference memory in mice.

Automated summary

Pannexin 1 (Panx1) is a widely expressed protein that forms plasma membrane channels allowing the passage of anions and moderate-sized signaling molecules. Previous studies have shown that activation of Panx1 channels contributes to various neurological disorders, and limited research suggests their involvement in hippocampus dependent learning. In this study, Panx1-null mice were used to investigate their role in working and reference memory and it was found that Panx1 channels in both astrocytes and neurons are critical for long-term spatial reference memory formation and consolidation. Recordings in hippocampal slices of Panx1-null mice showed a decrease in long-term potentiation and long-term depression, without affecting basal synaptic transmission or pre-synaptic paired-pulse facilitation.