HD is a late-onset, hereditary, neurodegenerative disorder that is caused by a CAG repeat expansion in the Huntingtin gene. No cure is available to date. Symptoms include extrapyramidal movement abnormalities, psychiatric features and cognitive decline, with the latter being reported as the most debilitating by patients. Using electrophysiological technology and a battery of object, place and context recognition cognitive tests we have found that both, long term potentiation, an electrophysiological correlate of learning and memory, and a hippocampal-dependent short term memory cognitive task are specifically perturbed in a knock-in mouse model for HD that carries 111 CAG repeats in exon1 of the murine huntingtin gene. Importantly, we find that the cognitive deficit can be rescued by a single dose of an α5-GABAA receptor antagonist, potentially providing a new therapeutic target. The project will: (i) explore when in development these deficits in cognition and synaptic plasticity occur, (ii) analyse the molecular mechanisms producing these dramatic changes in brain function, (iii) evaluate the efficacy of cognitive enhancing agents to reverse these deficits.