How is diverse sensory information encoded within the simple circuitry of the thalamus?

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The scientific communities' basic understanding of the brain is still too limited to offer any hope of comprehensively curing age-related cognitive decline and other common neurological disorders. To reach an adequate understanding of the basic mechanisms that control our brains, science is reliant on access to animal models that enable neuroscientists to study the cellular and molecular aspects of this most complex of organs. In this proposal, we aim to reach a greater understanding of how visual information is processed by our brains. Everything we see, hear and feel must pass through a relatively small part of our brain called the thalamus. We have known for several decades that a key role of the thalamus is to distribute salient features of our sensory world across the outer part of our brains called the neocortex to enable higher-order brain functions such as perception, cognition, generation of motor commands, spatial reasoning and language. Importantly, the thalamus stops relaying this sensory information to the neocortex when we are asleep. One of the most important steps in this process is the binding of a small inhibitory molecule called GABA (gamma amino butyric acid) to a type of membrane bound protein called the GABA-A receptor. The inhibitory neurotransmitter GABA is often released from local interneurons and high-resolution imaging studies from our laboratories have shown that thalamic interneurons are mainly found in a region of the thalamus called the dorsal lateral geniculate nucleus that receives sensory information from our eyes. We believe, therefore, that these interneurons have a specialised role to play in vision, but surprisingly we do not know what that role is. In most brain areas, the release of GABA is under the control of many distinct types of interneurons each doing slightly different jobs. For example, in the retina there are over 60 types of interneurons each responsible for converting the visual scene into electrical messages that are passed to the thalamus. Surprisingly, thalamic interneurons appear to be far less diverse, which rises the interesting question of how they may process the complex information arriving from the retina. To tackle this question, we first need to find out what type of visual information they are receiving. We have developed an innovative technique for doing this by using novel tracers that just label the inputs onto these thalamic interneurons. We now want to measure the electrical activity of these interneurons with specialized equipment that mimics how they would behave if they were receiving a visual stimulus. We are now in the unique position of being able to find out how these interneurons are controlled by visual input and discover for the first time what these cells are doing as they relay sensory information to the neocortex. Our work will go some way to explain why disturbances to the thalamus, for example during the ageing process, can be associated with cognitive decline especially during certain forms of vascular dementia. However, the central focus of this research is to reach a deeper understanding of how sensory information is encoded within the seemingly simple neuronal circuitry of the thalamus.