Division of Neuron-Glia Circuitry

 In vivo Ca²⁺ imaging of cortical astrocytes during resting state (right) and neuromodulator-driven activated state (left) in a G-CaMP7 transgenic mouse

Glial cells express G protein-coupled receptors (GPCRs) for mood-related neuromodulators, such as noradrenaline and acetylcholine; however, the impact of glial GPCR activation on brain functions remains to be investigated. One of the long-term goals of my laboratory is to understand the spatio-temporal dynamics of various glial GPCR signaling. To this end, we developed transgenic mice and viral vectors to express fluorescent functional indicators of GPCR second messengers (e.g. Ca²⁺ and cAMP). We will investigate how and when glial GPCR signaling occurs as well as the output of glial GPCR signaling on neural networks. The latter is in part probed by optogenetically activated GPCRs in behaving rodents.

Glycogen distribution in the mouse brain 

Astrocytes interface both synapses and blood vessels, thus they are in the ideal position to mediate energy supply from the vasculature to neurons. The astrocyte-neuron lactate shuttle hypothesis has been proposed to outline a scheme in which blood-supplied glucose is converted to lactate in astrocytes and shuttled to neurons. However, the exact picture of this system is yet to be described. Moreover, astrocytes are known to store glucose in the form of glycogen, which has been recognized critical for memory formation. We will characterize the cerebral distribution of glycogen in various behavioral and pathological conditions to gain insight into the realistic organization of brain energy metabolism. Currently, we have established glycogen immunohistochemistry to assess the spatial distribution of glycogen in fixed tissues. Ultimately, we aim to monitor long-term changes of cerebral energy metabolism using multiple imaging modalities.

Hippocampal theta LFP from mice raised in an enriched environment or an impoverished environment.

It is well established that exposure to an enriched environment alleviates both memory and emotional disturbances. We have investigated hippocampal local field potential (LFP) patterns in rats and mice raised in an enriched environment (ENR) or an impoverished, isolated (ISO) environment. As a result, we found that gamma activity is visibly enhanced in ENR rats and mice. Furthermore, we found that hippocampal ripple activity is attenuated in ISO IP₃R2-KO mice, the mouse strain that lacks GPCR-activated Ca²⁺ signaling in astrocytes.  While these results hints at a role of astrocytes in experience-dependent (long-term) plasticity, however, the exact nature of astrocytic signaling is unknown. We will disentangle possible astrocytic roles of experience-dependent plasticity by first looking at astrocytes’ second messenger signaling in behaving mice. The relevance of astrocytic GPCR signaling will be tested by cell-type specific opto- or pharmacogenetic manipulations.