Prefrontal cortex vs. V1: Profound differences that confer cognitive vulnerability

Tuesday, November 27, 2018 - 4:00pm to 5:00pm
CUIMC, Neurological Institute Auditorium, 1st floor, 710 West 168th Street
The association cortices atrophy in cognitive disorders such as schizophrenia and Alzheimer’s Disease, while the primary visual cortex (V1) is more resilient. What makes the association cortices so vulnerable? We have been comparing the neurons that subserve visuo-spatial working memory in the primate dorsolateral prefrontal cortex (dlPFC), to neurons in V1 that respond to visual stimuli, and have found marked differences in both neurotransmission and modulation. Neurons in V1 show classic responses: they rely heavily on AMPAR neurotransmission, and cAMP signaling enhances neuronal firing, likely by increasing glutamate release. In contrast, dlPFC neurons have little reliance on AMPAR, and instead depend on cholinergic permissive effects on NMDAR transmission. These neurons are very dependent on arousal state, and feedforward, cAMP-calcium signaling increases K+ channel opening to reduce firing, e.g. during stress. Dysregulation of cAMP-calcium signaling with advancing age leads to loss of neuronal firing and impaired working memory, as well as tau phosphorylation. Dysregulated calcium-cAMP signaling and tau hyperphosphorylation are also seen in the aging entorhinal cortex, the cortical area most vulnerable in Alzheimer’s Disease. These data show how studies of the primate cortex can help to illuminate the etiology of cognitive disorders.
Name: 
Amy F.T. Arnsten, PhD
Home Institution: 
Yale University School of Medicine
Event Types: 
Neurobiology Seminars