The Rob Jackson Lab
I am accepting MS but not PhD students.
Brain Glial Cells and Behavior
An important goal of contemporary neuroscience research is to define the neural circuits and synaptic interactions that mediate behavior. Mechanisms regulating circadian behavior and sleep, both rhythmic behaviors, are remarkably similar in Drosophila and mammals. The molecular biology of the circadian clock, for example, is virtually identical in flies and mammals, including humans (Jackson, 2011). In mammals, sleep is regulated by homeostatic and circadian processes, and the same is true of Drosophila sleep, which has characteristics in common with human sleep. In mammals and Drosophila, the neuronal circuits controlling circadian behavior or sleep have been the subject of intensive investigation, but roles for glial cells in the networks controlling rhythmic behavior are not as well understood (Jackson et al., 2020). Our lab was the first to document an important role for astrocytes in the physiological regulation of circadian behavior (Suh and Jackson, 2007; Ng et al, 2011, 2015, 2016). Others have shown that mammalian astrocytes also regulate circadian behavior and sleep. Our more recent studies have utilized Drosophila astrocyte gene expression profiling (Huang et al, 2013; Huang et al, 2015; Ng et al, 2016; You et al, 2021). as a basis for RNAi-based genetic screens to discover glial factors regulating circadian behavior or sleep (Ng and Jackson, 2015; Ng et al, 2016; You et al, 2021; Sengupta et al, 2019). In related studies, we have performed a genome-wide screen for small Drosophila non-coding RNAs (microRNAs) that regulate circadian behavior (You et al, 2018). That screen has revealed a number of microRNAs and target RNAs that are required in adult astrocytes for normal circadian behavior. Ongoing studies in the lab are focused on astrocyte-neuron communication in the regulation of Drosophila sleep.
Astrocyte-Neuron Communication Regulating Sleep
In both mammals and insects, it is known that astrocytes communicate with the neurons that regulate sleep. In my lab, we identified a small Ig-containing protein that regulated fly sleep (Sengupta et al, 2019) and appeared to be a secreted protein. Indeed, our studies have shown that it can be secreted from astrocytes, indicative of a glia-neuron communication function (Figure 1).
Figure 1. Signal for a GFP-tagged NKT protein within astrocytes of the optic lobe (arrowheads) is decreased in 90 s by 50-mM KCl treatment, indicative of secretion. Repo antibody signal shows glia of the brain (Sengupta et al., 2019).
In ongoing studies, we are interested in how this factor and others communicate with neurons that drive sleep. In addition, it is known that the astrocyte population is heterogeneous in both flies and mammals, and we have now identified many different subpopulations of astrocytes that regulate sleep (several shown in Figure 2). Using enhancer constructs that drive expression in limited subsets of astrocytes, we will perturb them to ask which features of sleep (amount and quality) are regulated by the different subpopulations.
Figure 2. Images of the fly brain showing the locations of three different astrocyte subpopulations, as identified by expression of green fluorescent protein.
In related studies, we are using molecular genetic methods – previously employed to examine neuron-to-neuron signaling – to identify sleep-regulating neurons with which astrocytes communicate. The aggregate of our studies will identify sleep-regulating gliotransmitters and demonstrate how astrocytes modulate the neuronal network driving sleep.