Neuronal mechanisms and neuropharmacology of perceptual learning

My friend Thomas is an artist but whenever we look at the same things he illuminates an important problem in neuroscience. He sees things differently from me. In bland walls he sees the plaster’s structure nicely contrasting the weathered chromium green of a nearby car. Thus, his pictures of boring environments make great paintings. Thomas’ exceptional visual abilities have been honed by years of training and practice as an artist. But those abilities must be supported by real differences in his brain. Where do these differences reside? How do they come about? And what are they?
To become better at ‘seeing things’ and at discrimination tasks is referred to as perceptual learning. The mechanisms that mediate perceptual learning and the locations in the brain are still poorly understood.
We will investigate (1) where in the brain perceptual learning occurs, and whether there a hierarchy of perceptual learning? (2) How does attention influence perceptual learning? (3) Which brain chemicals mediate perceptual learning? Answers to these questions will improve our understanding of learning in general and may pave the way to better regeneration of brain function following brain injury and better therapy for learning disorders.

Performance in perceptual tasks can improve well beyond the asymptotic levels when a new context is introduced, a phenomenon termed context-enabled learning. Adini et al. (Nature. 2002, 415:790) demonstrated this in a visual contrast discrimination task and proposed a computational model where a combination of hebbian and anti-hebbian synaptic learning rules triggered by the new context induce plasticity in early visual areas. We aim to study the neuronal basis and mechanisms of context-sensitive learning by combining monkey psychophysics with neurophysiological and neuropharmacological techniques. We will study learning induced changes of neuronal contrast sensitivity in V1 and V4 by applying ideal observer analyses to single neuron and neuronal population data. We will use chronically implanted microelectrode arrays and a novel pipette-electrode combination to study the neuronal changes in V1 and V4 as learning progresses, as well as its susceptibility to neuropharmacological intervention. This will allow comparing monkey psychophysical and simultaneously determined neuronal contrast thresholds while learning occurs. Local application of specific neuromodulator/transmitter antagonists/agonists will reveal molecular and pharmacological mechanisms underlying synaptic plasticity during perceptual learning. These studies will be performed during passive viewing and while monkeys engage in spatial attention tasks. We will influence the local balance of excitatory-inhibitory interactions and test whether a disruption of their equilibrium is sufficient to trigger plastic changes (in the absence of task performance). We will additionally apply cholinergic and/or NMDA antagonists at locations where learning should occur during the learning phase, aiming to block its occurrence. The results will make an important contribution to our understanding of influential, but currently unproven theories regarding the loci, mechanisms, and occurrence of perceptual learning.