The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, especially when the removal is on the left side. Children may benefit most from surgery, because brain plasticity may facilitate post-surgical reorganization, and seizure cessation may promote cognitive development. However, the long-term impact of this intervention in children is not known. We examined memory function in 53 children (25 males, 28 females) who were evaluated for epilepsy surgery: 42 underwent unilateral temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11 were treated only pharmacologically. Average follow-up was 9 years (range 5-15). Post-surgical change in visual and verbal episodic memory, and semantic memory at follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were analysed to extract hippocampal and resection volumes, and evaluate post-surgical temporal lobe integrity. Language lateralization indices were derived from functional magnetic resonance imaging. There were no significant pre- to postoperative decrements in memory associated with surgery. In contrast, gains in verbal episodic memory were seen after right temporal lobe surgery, and visual episodic memory improved after left temporal lobe surgery, indicating a functional release in the unoperated temporal lobe after seizure reduction or cessation. Pre- to post-surgical change in memory function was not associated with any indices of brain structure derived from MRI. However, better verbal memory at follow-up was linked to greater post-surgical residual hippocampal volumes, most robustly in left surgical participants. Better semantic memory at follow-up was associated with smaller resection volumes and greater temporal pole integrity after left temporal surgery. Results were independent of post-surgical intellectual function and language lateralization. Our findings indicate post-surgical, hemisphere-dependent material-specific improvement in memory functions in the intact temporal lobe. However, outcome was linked to the anatomical integrity of the temporal lobe memory system, indicating that compensatory mechanisms are constrained by the amount of tissue which remains in the operated temporal lobe. Careful tailoring of resections for children undergoing epilepsy surgery may enhance long-term memory outcome.

Homeostatic plasticity keeps neuronal spiking output within an optimal range in the face of chronically altered levels of network activity. Little is known about the underlying molecular mechanisms, particularly in response to elevated activity. We report that, in hippocampal neurons experiencing heightened activity, the activity-inducible protein kinase Polo-like kinase 2 (Plk2, also known as SNK) was required for synaptic scaling-a principal mechanism underlying homeostatic plasticity. Synaptic scaling also required CDK5, which acted as a "priming" kinase for the phospho-dependent binding of Plk2 to its substrate SPAR, a postsynaptic RapGAP and scaffolding molecule that is degraded following phosphorylation by Plk2. RNAi knockdown of SPAR weakened synapses, and overexpression of a SPAR mutant resistant to Plk2-dependent degradation prevented synaptic scaling. Thus, priming phosphorylation of the Plk2 binding site in SPAR by CDK5, followed by Plk2 recruitment and SPAR phosphorylation-degradation, constitutes a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity.