LearnMamBo · Neuronal dynamics of learning and memory in the mammillary body

At the heart of our individual personalities lie our memories – be it our first time riding a bike, the school graduation ceremony, or yesterday’s football match. Yet, it is estimated that in the coming decades up to 150 million people worldwide will suffer from dementia. To tackle this surge and identify therapeutic interventions, a thorough understanding of the neuronal mechanisms underlying long-term memory storage is necessary. Research in humans and rodents has identified the hippocampus as the brain’s preeminent structure for memory processing. Yet, for memories to become permanently stored and correctly retrieved, the hippocampus needs to communicate with the rest of the brain. One of the main projection targets of the hippocampus is the mammillary body (MB). Over a century of clinical research and lesion studies in rats have established the importance of the MB to form and retrieve long-lasting memories but its peculiar anatomical location has prevented research to uncover the mechanisms underlying this role.In this research programme, we will reveal the role of the MB in memory processing at a cellular, circuit, network, and behavioural level in mice. First, we will make use of recently established genetic tools to ascribe precise causal roles for memory processing to individual mouse MB subnuclei. Next, we will leverage my extensive experience with in vivo two-photon microscopy to image calcium activity from identified MB neurons across multiple days of learning. We will then combine these tools to elucidate the role of reciprocal brainstem inhibition. Lastly, we will use high-density silicon probe recordings to simultaneously record activity across cortical, thalamic and hippocampal sites connected to the MB, as animals are actively engaged in memory tasks.Overall, our research will deliver mechanistic insights into how the MB aids memory processing, which will prove critical for our understanding of how the brain can form life-long memories.