Seminars

Biological neural networks can represent information in the collective action potential discharge of neurons, and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the neurons. This lecture will first summarize our investigations of the molecular and biochemical mechanisms that change synaptic function to persistently store spatial memory in the rodent hippocampus. I will then report on how entorhinal cortex-hippocampus circuit function changes during cognitive training that creates memory, as well as learning to learn in mice. I will then describe how the hippocampus system operates like a competitive winner-take-all network, that, based on the dominance of its current inputs, self organizes into either the encoding or recollection information processing modes. We find no evidence that distinct cells are dedicated to those two distinct functions, rather activation of the hippocampus information processing mode is controlled by a subset of dentate spike events within the network of learning-modified, entorhinal-hippocampus excitatory and inhibitory synapses.

Work in my laboratory is based on the assumptions that we do not know yet how all physiological functions are regulated and that mouse genetics by allowing to identify novel inter-organ communications is the most efficient ways to identify novel regulation of physiological functions. We test these two contention through the study of bone which is the organ my lab has studied since its inception. Based on precise cell biological and clinical reasons that will be presented during the seminar we hypothesized that bone should be a regulator of energy metabolism and reproduction and identified a bone-derived hormone termed osteocalcin that is responsible of these regulatory events. The study of this hormone revealed that in addition to its predicted functions it also regulates brain size, hippocampus development, prevents anxiety and depression and favors spatial learning and memory by signaling through a specific receptor we characterized. As will be presented, we elucidated some of the molecular events accounting for the influence of osteocalcin on brain and showed that maternal osteocalcin is the pool of this hormone that affects brain development. Subsequently and looking at all the physiological functions regulated by osteocalcin, i.e., memory, the ability to exercise, glucose metabolism, the regulation of testosterone biosynthesis, we realized that are all need or regulated in the case of danger. In other words it suggested that osteocalcin is an hormone needed to sense and overcome acute danger. Consonant with this hypothesis we next showed this led us to demonstrate that bone via osteocalcin is needed to mount an acute stress response through molecular and cellular mechanisms that will be presented during the seminar. overall, an evolutionary appraisal of bone biology, this body of work and experiments ongoing in the lab concur to suggest 1] the appearance of bone during evolution has changed how physiological functions as diverse as memory, the acute stress response but also exercise and glucose metabolism are regulated and 2] identified bone and osteocalcin as its molecular vector, as an organ needed to sense and response to danger.