Suppression of neuronal AMPKβ2 isoform impairs recognition memory and synaptic plasticity

AMP-activated protein kinase (AMPK) is an alpha beta gamma heterotrimer protein kinase that functions as a molecular sensor to maintain energy homeostasis. Accumulating evidence suggests a role of AMPK signaling in the regulation of synaptic plasticity and cognitive function; however, isoform-specific roles of AMPK in the central nervous system (CNS) remain elusive. Regulation of the AMPK activities has focused on the manipulation of the alpha or gamma subunit. Meanwhile, accumulating evidence indicates that the beta subunit is critical for sensing nutrients such as fatty acids and glycogen to control AMPK activity. Here, we generated transgenic mice with conditional suppression of either AMPK beta 1 or beta 2 in neurons and characterized potential isoform-specific roles of AMPK beta in cognitive function and underlying mechanisms. We found that AMPK beta 2 (but not beta 1) suppression resulted in impaired recognition memory, reduced hippocampal synaptic plasticity, and altered structure of hippocampal postsynaptic densities and dendritic spines. Our study implicates a role for the AMPK beta 2 isoform in the regulation of synaptic and cognitive function.