Human cognition depends upon slow-firing neurons

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 Feb. 20 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 signaling 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.

Earlier studies have shown these types of NMDA receptors are often altered in patients with schizophrenia. The Neuron study suggests that those suffering from the disease may be unable to hold onto a stable view of the world. Also, these receptors seem to be altered in Alzheimer’s patients, which may contribute to the cognitive deficits of dementia.

The lab of Dr. John Krystal, chair of the department of psychiatry at Yale, has found that the anesthetic ketamine, abused as a street drug, blocks NMDA receptors and can mimic some of the symptoms of schizophrenia. The current study in Neuron shows that ketamine may reduce the firing of the same higher-order neural circuits that are decimated in schizophrenia. 

“Identifying the receptor needed for higher cognition may help us to understand why certain genetic insults lead to cognitive impairment and will help us to develop strategies for treating these debilitating disorders,” Arnsten said.

Cognitive Connectivity

Credit: Emmett McQuinn, Theodore M. Wong, Pallab Datta, Myron D. Flickner, Raghavendra Singh, Steven K. Esser, Rathinakumar Appuswamy, William P. Risk, and Dharmendra S. Modha; IBM Research - Almaden  -(First place winners in the illustration category of the 2012 International Science & Engineering Visualization Challenge)

Cognitive Computing researchers at IBM are developing a new generation of “neuro-synaptic” computer chips inspired by the organization and function of the brain. For guidance into how to connect many such chips in a large brain-like network, they turn to a “wiring diagram” of the monkey brain as represented by the CoCoMac database. In a simulation designed to test techniques for constructing such networks, a model was created comprising 4173 neuro-synaptic “cores” representing the 77 largest regions in the macaque brain. The 320749 connections between the regions were assigned based on the CoCoMac wiring diagram. This visualization is of the resulting core-to-core connectivity graph. Each core is represented as an individual point along the ring; their arrangement into local clusters reflects their assignment to the 77 regions. Arcs are drawn from a source core to a destination core with an edge color defined by the color assigned to the source core.