Human cognition depends upon slow-firing neurons, Yale researchers find

Good mental health and clear thinking depend upon our ability to store and manipulate thoughts on a sort of ''mental sketch pad.''

In a new study, Yale School of Medicine researchers describe the molecular basis of this ability - the hallmark of human cognition - and describe how a breakdown of the system contributes to diseases such as schizophrenia and Alzheimer's disease.

''Insults to these highly evolved cortical circuits impair the ability to create and maintain our mental representations of the world, which is the basis of higher cognition,'' said Amy Arnsten, professor of neurobiology and senior author of the paper published in the 20 February issue of the journal Neuron.

High-order thinking depends upon our ability to generate mental representations in our brains without any sensory stimulation from the environment. These cognitive abilities arise from highly evolved circuits in the prefrontal cortex.

Mathematical models by former Yale neurobiologist Xiao-Jing Wang, now of New York University, predicted that in order to maintain these visual representations the prefrontal cortex must rely on a family of receptors that allow for slow, steady firing of neurons.

The Yale scientists show that NMDA-NR2B receptors involved in glutamate signalling regulate this neuronal firing.  These receptors, studied at Yale for more than a decade, are responsible for activity of highly evolved brain circuits found especially in primates.