HOW DO GLIA HELP WIRE THE BRAIN?
Plasticity as we grow
Ever wondered why children can learn languages with relative ease, but adults struggle to string together even one sentence in a new language? During development, neural circuits in the brain undergo brief windows of heightened plasticity, or critical periods, to accommodate rapid learning. In adulthood, this plasticity is largely limited. Why is plasticity lost over time?
Role of excitatory/inhibitory balance and critical period timing.
Environmental triggers of critical period closure
We recently identified astrocytes, a prominent glial cell in the brain, as key cellular brakes on critical period plasticity (Ackerman et al. 2021). The Ackerman lab uses zebrafish and fruit fly to define circuit-specific glia-neuron signaling networks that suppress developmental plasticity and to determine how loss of these brakes impacts circuit structure, function, and behavior. We combine optogenetics, connectomics, super-resolution imaging, electrophysiology, and high-throughput behavioral analyses to understand how glia shape developmental plasticity, from synapses to circuits.
Cytoskeletal features of structural plasticity
Physiological significance of critical periods for motor circuit structure/function
Establishing vertebrate-specific critical period models
Glia-glia (astrocyte, microglia, oligodendrocyte) communication and critical period timing
Plasticity as we age
Memory loss in a common part of aging, and it is frustrating! The market is flooded with apps (e.g. Luminosity or Sudoku) touted to improve or regain memory and focus through puzzle solving. While it is tempting to seek to unleash plasticity as a proverbial fountain of youth, heightened levels of plasticity are linked to both neurodevelopmental disorders such as epilepsy, and age-related neurodegeneration. Could changes in plasticity during childhood increase a person’s likelihood for neurodegeneration?
Intersection between developmental activity, glial signaling, and motor circuit maintenance
Generation and validation of human disease variants in zebrafish
The Ackerman lab uses fruit fly and zebrafish to define the link between critical period plasticity and susceptibility to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, aka Lou Gehrig’s disease). Specifically, we are testing the hypothesis that changes in developmental plasticity, without essential limitations imposed by glia, predisposes circuits to disrepair. We combine cutting-edge sequencing strategies, CRISPR/Cas9 mutagenesis, optogenetics, in vivo imaging, and drug screening to propel our work from the bench to the bedside.