The Effect of Ethanol on the Neuronal Subserving of Behavior in the Hippocampus

We have previously shown that both acute and chronic ethanol treatment depresses neural activity, specifically in the cingulate cortex. Minor influences were found in the motor cortex. The acute effect of ethanol in the hippocampus was intermediate to those in the cingulate and motor cortices. In the present study, we concentrate on the chronic effects of ethanol on the hippocampus. We demonstrate how the neuronal activity underlying food-acquisition behavior is modified after chronic ethanol treatment, and how the hippocampus subserves formation of newly-formed alcohol-acquisition behavior. Neuronal activity in CA1 was more sensitive to chronic ethanol than the Dg area. Acute administration of ethanol had a normalizing effect on the chronically-treated animals: their performance and the hippocampal neural activity approached a normal range. The sets of neurons involved in food-acquisition behavior formed before chronic ethanol treatment, and those involved in alcohol-acquisition behavior formed after treatment significantly overlapped supporting the view that the neuronal mechanisms of pre-existing behavior provide the basis for the formation of new behavior. Additionally, we also discovered alcohol-acquisition selective neurons. Assuming that the formation of new neuronal specializations underlies learning, we believe that alcohol-selective neurons are specialized during the formation of alcohol-acquisition behavior. Our data demonstrate several new findings on the effect of acute and chronic ethanol on hippocampus activity, and how the neuronal activity relates to behavior before and after ethanol treatment.

Nanoparticle based inner ear therapy

Synthetic nanoparticles can be used to carry drugs, genes, small interfering RNA （siRNA） and growth fac-tors into the inner ear, to repair, restore and induce cellular regeneration. Nanoparticles （NPs） have been developed which are targetable to selected tissue, traceable in vivo, and equipped with controlled drug/gene release. The NPs are coated with a “stealth” layer, and decorated with targeting ligands, markers, transfection agents and endosomal escape peptides. As payloads, genes such as the BDNF -gene, Math1 -gene and Prestin -gene have been constructed and delivered in vitro. Short-hairpin RNA has been used in vitro to silence the negative regulator of Math1, the in-hibitors of differentiation and DNA binding. In order to facilitate the passage of cargo from the middle ear to the inner ear, the oval window transports gadolinium chelate more effciently than the round window and is the key element in introducing therapeutic agents into the vestibule and cochlea. Depending upon the type of NPs, different migration and cellular internalization pathways are employed, and optimal carriers should be designed depending on the cargo. The use of NPs as drug/gene/siRNA carriers is fascinating and can also be used as an intraoperative adjunct to cochlear implantation to attract the peripheral processes of the cochlear nerve.