Question
Does enhancing GluN2B-containing NMDA receptor activity at cortico-striatal synapses restore 30-40 Hz beta-band synchrony and improve motor sequence learning in early Huntington's disease?
Falsifiable prediction from high-scoring hypothesis (score=0.723, gene=GRIN2B). Hypothesis: Does enhancing GluN2B-containing NMDA receptor activity at cortico-striatal synapses restore 30-40 Hz beta-band synchrony and improve motor sequence learning in early Huntington's disease? Success criteria: 1. GRIN2B activity enhancement (CIQ or similar) increases 30-40 Hz LFP power in striatum by >40% in HD model mice. 2. Motor sequence learning (accelerating rotarod) improves by >25% in treated HD mice vs vehicle. 3. Striatal medium spiny neuron (MSN) firing regularity (interspike interval CV) normalizes to within 20% of WT. 4. No excitotoxicity: caspase-3+ neurons remain <5% in treated vs vehicle HD mice.