title: Huntingtin is critical both pre- and postsynaptically for long-term learning-related synaptic plasticity in Aplysia.
abstract: Patients with Huntington's disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington's disease. 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. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.
authors: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America.
authors: Yun-Beom
authors: YB
authors: Choi
authors: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
authors: Beena M
authors: BM
authors: Kadakkuzha
authors: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
authors: Xin-An
authors: XA
authors: Liu
authors: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
authors: Komolitdin
authors: K
authors: Akhmedov
authors: Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America; Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America; Kavli Institute for Brain Science, College of Physicians and Surgeons of Columbia University, New York, New York, United States of America.
authors: Eric R
authors: ER
authors: Kandel
authors: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
authors: Sathyanarayanan V
authors: SV
authors: Puthanveettil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein; D057567:Memory, Long-Term; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009473:Neuronal Plasticity; D013569:Synapses / Q000737:chemistry / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins