RT Journal Article
SR Electronic
T1 Channel-mediated astrocytic volume transient is required for synaptic plasticity and spatial memory
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2025.02.03.636214
DO 10.1101/2025.02.03.636214
A1 Woo, Junsung
A1 Drew, Victor James
A1 Lee, Jung Moo
A1 Koh, Wuhyun
A1 Won, Joungha
A1 Lee, C. Justin
YR 2025
UL http://biorxiv.org/content/early/2025/02/03/2025.02.03.636214.abstract
AB Astrocytes, known for their support roles, are emerging as active participants in synaptic plasticity and cognitive functions. Astrocytes actively regulate synaptic plasticity and memory through dynamic volume transients. Our previous research identified several key molecules, including TREK-1, TRPA1, and Best1 ion channels, as well as the gliotransmitter BDNF, as critical components of astrocytic volume transients. However, the precise mechanisms by which these volume transients influence synaptic plasticity and memory remain poorly understood. In this study, we investigate the roles of TREK-1 and TRPA1 in astrocytic volume dynamics and their downstream effects. Using intrinsic optical signal imaging, electrophysiology, and behavioral assays, we demonstrate that neuronal stimulation induces astrocytic swelling, initiated by K+ uptake through TREK-1 channels and regulated by Ca2+ influx via TRPA1 channels. This swelling is closely associated short- and long-term potentiation, and is accompanied by the release of BDNF, which restores long-term potentiation under conditions of calcium sequestration during astrocytic calcium clamping experiments. Disruption of astrocytic volume transient associated ion channels results in significant deficits in spatial memory, as evidenced by impairments in object-place recognition and passive avoidance tasks. Furthermore, these channels were found to modulate the synaptic plasticity. These findings reveal astrocytic volume transients and BDNF as pivotal modulators of synaptic plasticity and memory, as well as potential therapeutic targets for addressing memory dysfunctions.Competing Interest StatementThe authors have declared no competing interest.