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Stanton, P. K.

Publications and source records attributed to Stanton, P. K..

2 recordsLinked to original sources

Astrocyte and neuronal Panx1 support long-term reference memory in mice

Pannexin 1 (Panx1) are ubiquitously expressed proteins that form plasma membrane channels permeable to anions and moderate sized signaling molecules (e.g., ATP, glutamate). In the nervous system, activation of Panx1 channels have been extensively shown to contribute to distinct neurological disorders (epilepsy, chronic pain, migraine, neuroAIDS, etc.) but knowledge of 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 8-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 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.

neuroscience↗

Developmental time course of SNAP-25 isoform regulation of hippocampal long-term synaptic plasticity and hippocampus-dependent learning

SNAP-25 is essential in activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During development and adulthood, SNAP-25 appears to have differential influences on long- and short-term synaptic plasticity in the hippocampus. The involvement of SNAP-25 in this process may be altered by two different splice variants expressed in adolescences versus adulthood in hippocampal neurons. This study suggests that the adolescent isoform, SNAP-25a can contribute to developmental regulation of the expression of LTD and LTP. In mice deficient in SNAP-25b, the adult isoform, Schaffer collateral-CA1 synapses showed slower release kinetics, reduced initial release probabilities, decreased LTP and enhanced LTD at 1 month. By 4 months of age, when mice have fully developed in the absence of SNAP-25b, the gene targeted mice appear to have compensated for the lack of the adult SNAP-25b isoform. Moreover, hippocampal-dependent training reversed reductions in LTP, but not LTD, seen at 1 month. In 4 month old adult mice, training prevented the compensatory reversal of LTD that had been observed prior to training. These findings support the hypothesis that immature SNAP-25a plays a strong role in the expression of plasticity at Schaffer collateral-CA1 synapses in adolescent mice, but compensatory mechanisms that reverse alterations in synaptic plasticity once mice reach adulthood.

neuroscience↗