Yun-Beom Choi; Beena M. Kadakkuzha; Xin-An Liu; Komolitdin Akhmedov; Eric R. Kandel; Sathyanarayanan V. Puthanveettil

“ The autosomal dominant inheritance pattern of Huntington’s disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington’s disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. ”

“ Huntington’s disease (HD) is caused by a mutation that expands the number of trinucleotides CAG repeats in a gene leading to an expansion of polyglutamine stretch in huntingtin, the encoded protein (The Huntington’s Disease Collaborative Research Group, 1993) . HD is a neurodegenerative disorder characterized by involuntary movements, emotional disturbance, and cognitive impairment [1] . In HD, early cognitive deficits occur many years prior to overt motor deficits [2] , a finding also observed in a transgenic mouse model of HD [3] . ”

“ Error bars are SEM. SN: sensory neuron, MN: Motor neuron. Having established that antisense oligonucleotides are able to knock down ApHTT mRNA levels in sensory neurons, we examined whether the down regulation of ApHTT mRNA by antisense oligonucleotides in the presynaptic sensory neurons affects basal synaptic transmission in the sensory-motor neuron synapse by measuring excitatory postsynaptic potentials (EPSPs) at 24 hours after oligonucleotides injection (50 ng/μl) to the presynaptic sensory neurons. ”