Optical interrogation of hippocampal dentate granule circuit dynamics in health and disease
Understanding the cellular and synaptic basis of memory remains a central goal of modern neuroscience. Physical traces of memory exist as an enduring, experience-dependent change in neural activity in response to learning. In the hippocampus, a key region of the mammalian brain involved in memory formation and recall, new neurons are continually generated in the dentate gyrus (DG) where they form an integral part of the existing functional circuitry. Despite its key position in the hippocampal formation, however, the function of DG and its adult-born neurons in vivo has not been carefully investigated. Here, by applying transgenic and optogenetic approaches – including multicolour genetically encoded activity reporters – together with longitudinal two-photon imaging, we aim to study functional dynamics and plastic changes in DG in health and disorder. We propose that activity patterns in DG cell populations show activity-dependent changes during learning and construct a cellular and circuit basis for contextual memory engrams. We will also investigate how synaptic alterations in excitation-inhibition balance and defects in adult neurogenesis in DG lead to neurological disorders such as Rett syndrome.