This project investigated the neural circuitry regulating intake of alcohol and sugary solutions in mouse models. The focus was a group of nerves in the hindbrain which expressed the receptor for oxytocin (oxytocin receptor-expressing neurons in the parabrachial nucleus of OxtrPBN neurons), which was previously discovered as playing a key role in controlling fluid satiation. The major findings from this project were that artificially activating these OxtrPBN neurons decreased the initial intake of alcohol, sugary drinks, artificial sweetener (saccharin) and salty solutions after mice had been dehydrated overnight, but they did not decrease the longer-term intake of highly palatable or highly caloric solutions. These results suggested that OxtrPBN neurons play a key role in the homeostatic or ‘fluid balance’ response after dehydration.
It was also found that activating these OxtrPBN neurons decreased anxiety in mice. These are important results because they demonstrate that OxtrPBN neurons are targets for decreasing alcohol and sugary drinks, without increasing anxiety. Looking more broadly throughout the hindbrain, it was observed that different subdivisions of the hindbrain parabrachial nucleus responded to different aspects of fluid intake: the dorsolateral subdivision was involved in all types of fluid satiation; the external lateral subdivision was involved in caloric regulation; and the central lateral subdivision was involved in regulating highly palatable and sweetened solutions. This suggests that we might be able to target different subdivisions to control specific aspects of fluid intake.
Further investigations examined the interaction between feeding and drinking neural circuitry in the brain. It was demonstrated that the feeding-associated peptide called agouti-related peptide (or AgRP) inhibited firing of OxtrPBN neurons in a concentrated-related manner using the technique of electrophysiology. This result aids in our understanding of how feeding and fluid neural circuits interact to control intake of food and drink.
Viral tracing mechanisms were used to map out the neural circuitry. Here, it was observed that the OxtrPBN neurons sent projections to several fluid-related brain regions and indirectly activated other fluid related brain regions. This is important in constructing a neural circuit map of fluid satiation.
