Alex Major, PhD


Probing the cortical circuits that prevent sensory overload


Earl Miller, Ph.D., Nancy Kopell, Ph.D.

Biographical Information:

Alex received BMSc with Honors Specialization in Physiology and Pharmacology, MSc Neuroscience, and PhD Neuroscience at The University of Western Ontario, in London, Ontario Canada. His graduate work focused on the ability of prefrontal neurons to represent working memory and cognitive information in nonhuman primates. Using local iontophoretic injection of drugs, they tested the function of cholinergic receptors in prefrontal neurons during cognitive behavior. They found cholinergic receptor stimulation is required for optimal cognitive representation and may have differing effects between pyramidal and nonpyramidal neurons. In contrast the dominant theory, they reported that muscarinic M1 receptors were suppressive to neuronal activity in prefrontal cortex.

Current Work:

Individuals with autism can experience sensory overload, induced by excessive sensory inputs such as repetitive sounds, light, and touch. In neurotypicals, the brain suppresses constant or repetitive stimuli. Sensory overload may result from a lack of this habituation. Our model of brain function suggests sensory input is carried by brain rhythms know as gamma, which are primarily found in the upper layers of the cortex. In contrast, alpha/beta rhythms are predominantly found in deeper layers and can suppress gamma rhythms. Deficient alpha/beta rhythms have been reported in autism. We hypothesize this deficient alpha/beta may be the cause of disrupted habituation and therefore sensory overload in autism. These theories of brain function are based on observed correlations and lack tests of causality that directly manipulate brain circuitry. We have developed a technique to selectively shut down neurons in upper or deep layers of cortex. We believe we can simulate sensory overload in rhesus monkeys by suppressing neurons in deep layers of rhesus monkeys. This is predicted to decrease alpha/beta activity and thus increase gamma activity and processing of sensory inputs. This will directly test a hypothesized mechanism of sensory overload, perhaps leading research towards improved symptom management.

Keywords: multi-contact laminar electrophysiology, pharmacology, nonhuman primates, predictive coding, GABA