As a kid growing up in the greater Philadelphia area, Megan Carey was always fascinated by optical illusions and other brain puzzles. “I remember as a child wondering whether other people saw colors the same way that I saw colors,” she says. After flirting with the idea of majoring in physics, she ended up in the lab of neuroscientist David Bodznick at Wesleyan University, where she studied how skates—fish relatives of rays and sharks—could differentiate between electrical signals produced by nearby prey and those produced by their own movements. She found that, through repeated associations, skates’ neurons learned to tell the difference between self-generated electrical fields and similar signals coming from the outside world.
“Studying that system got me interested in simple forms of learning,” she says.
METHODS: As a PhD student in Stephen Lisberger’s lab at the University of California, San Francisco, Carey continued to probe how neurons process learning by tracking the eye movements of monkeys as they were presented with moving dots.
Monkeys quickly learn to anticipate the trajectory of moving dots with their eyes, but Carey wanted to see what would happen if she directly stimulated the neurons responsible for teaching the animals where to look and for correcting the brain if the eyes failed to follow the moving target. “If we could manipulate the activity of those neurons without moving any visual targets,” she asked herself, “would that be enough to teach a monkey a learned eye movement?”
She found that it was. By applying a current to certain neurons in a region of the brain called the Visual Area MT—which researchers had previously shown to detect different directions of visual motion—she was able to mimic the same outcome as a monkey learning to track an actual moving target.1
“She was an intellectual leader and a real stabilizing force at the lab,” says Lisberger.
RESULTS: As a postdoc, Carey traded in her in vivo monkey experiments for studying synaptic plasticity in mouse brain slices in a cellular and neurophysiology lab at Harvard, where she continued researching instructive signals in the brain, albeit on a cellular level. She showed that neuromodulators such as noradrenaline can indirectly influence synaptic plasticity in the cerebellum—the brain’s sensorimotor coordination center, where simple forms of associative learning take place—by acting on “instructive” synapses that then change neighboring nervous connections.2
Carey also found a new putative mechanism for the regulation of long-term plasticity by the type 1 cannabinoid receptor (CB1R) in a specific cerebellar cell type known as a granule cell.3
DISCUSSION: “She can go from molecules to cells to systems,” says Rui Costa, a neuroscientist colleague at the Champalimaud Centre for the Unknown in Lisbon, Portugal. In 2008, Costa helped recruit Carey to the neuroscience program at the institute, which opened its doors in late 2010. “We wanted to recruit very bright young people, and she was exactly what we wanted,” he says—“someone very well grounded that can think across levels in neuroscience.”
- M.R. Carey et al., “Instructive signals for motor learning from visual cortical area MT,” Nature Neuroscience, 8:813-19, 2005. (Cited 22 times)
- M.R. Carey, W.G. Regehr, “Noradrenergic control of associative synaptic plasticity by selective modulation of instructive signals,” Neuron, 62:112-22, 2009. (Cited 8 times)
- M.R. Carey et al., “Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses,” J Neurophysiol, 105:958-63, 2011. (Cited 4 times)