The role of synchronized oscillatory neural activity in vomeronasal chemosensation

Smell is the dominant sense for many animals, and especially for rodents such as mice. It not only helps them find food and alerts them to the presence of predators, but also conveys information about the sex, age, health status and individual identity of other mice. In doing so, it has important influence over many basic behavioural responses such as sexual behaviour, parental behaviour, territorial behaviour and aggression. Information about smell is processed by relatively simple circuits, which have formed the basis for the evolution of higher brain functions. Understanding the way that the brain handles this information provides an insight into fundamental brain functions. For example, female mice are able to recognise their mate by their smell. The changes in the brain underlying this simple form of learning involve particular connections between identified brain cells at the first stage of sensory processing, in a region called the accessory olfactory bulb. This degree of localisation of a memory trace is highly unusual in mammals and provides a valuable opportunity to study the way that learning affects the processing of sensory information. Brain cells do not function alone, but communicate with each other in large networks of interconnected cells. It has become apparent over the last twenty years that the activity in such networks is coordinated so that cells communicate more effectively when their activity is synchronized. It is this synchronization of activity that produces the brain waves that can be recorded from the surface of the scalp when we sleep. The aim of this project is to determine how this synchronized activity is produced and regulated in the regions of the female mouse brain that respond to the smell of their mate. This will be achieved by examining how drugs that alter the communication between brain cells affect the frequency and size of the brain waves. The relationship between the brain waves, the activity of individual brain cells and the behaviour of the mice will be determined to see how this changes after the female has learned to recognise her mate. This information will be used to test the current hypothesis for how mate recognition can be achieved by such a simple neural system. The information generated by this project will further our understanding of how the brain works in other species, including humans. In particular it will provide data that can be used in the construction of mathematical models of brain function. A greater understanding of how synchronous neural activity changes during learning will provide greater understanding of how sensory information is processed and remembered by the brain. Furthermore, it will increase our understanding of the brain regions governing reproductive behaviour, and may eventually lead to new opportunities for humane methods to control rodent populations.

Oscillations in the activity of neural networks are believed to synchronize and co-ordinate neural activity both within and across cortical brain areas. This project aims to determine the neural mechanisms underlying such oscillations in a simple cortical system; and how changes in oscillatory dynamics following learning affect the transmission of information influencing reproductive physiology and behaviour. The memory formed by female mice to the chemosignals of their mate is one of the best-understood examples of mammalian learning. This can be explained by a simple hypothesis in which a selective increase in feedback inhibition, at the level of the accessory olfactory bulb (AOB), disrupts the transmission of the learned signal from the mating male. Mathematical modelling predicts that an increase in this feedback inhibition will result in a change in the frequency of oscillatory neural activity in the AOB. This could shift AOB output from the optimum frequency for activating oscillatory neural networks in the amygdala that control neuroendocrine output. Wavelet analysis will be used to determine the effects of disrupting intrinsic inhibitory feedback, and long-loop feedback via the amygdala, on the oscillatory local field potential recorded from the AOB in freely behaving mice. The effect of noradrenaline in modulating AOB oscillatory activity will be related to its essential role in memory formation at mating. The relationship between LFP oscillations in the amygdala and the frequency of afferent stimulation will be determined to test the hypothesis that learning disrupts transmission of information by decoupling the AOB and amygdala oscillatory dynamics. This information will provide important data for mathematical modelling of cortical functioning, and increased understanding of brain networks controlling reproductive behaviour in rodents.