Cognitive and kinematic markers of ketamine effects in behaving non-human primates.

Ketamine, which alters synaptic transmission via NMDARs, affects cognitive functions, but its impact on motor control in the brainstem is selective. In primates, ketamine injection substantially decreased the deceleration of horizontal saccades, which rely on glycine-NMDAR-gated currents, while vertical saccade deceleration, controlled by GABA currents, remained largely unaffected. This indicates that despite general circulation of the drug, the motor brainstem generator circuit differentially maintains saccade kinematics. The results provide distinct markers for estimating NMDAR-gated specificity in the prefrontal cortex versus GABA circuit specificity.

Study at a glance

Abstract

Ketamine is widely used to probe cognitive functions relying on the properties of methyl-D-aspartate receptor (NMDAR) synaptic transmission. Numerous works have proved that cognitive performance and adjustments in the decision or perceptual domains are affected after ketamine injection in general circulation of primates. Here, we take advantage of that in the brain stem; horizontal saccade deceleration is controlled by glycine-NMDAR-gated current, while gamma-aminobutyric acid (GABA) current controls vertical deceleration to demonstrate that despite general circulation level manipulation of NMDAR synaptic transmission, the kinematic of the saccade appeared to be in the motor brainstem generator circuit differentially maintained. The results show that the deacceleration of the saccade elicited toward a horizontal target was substantially decreased, while the deacceleration of a vertical saccade remained largely unaffected. These results provide functional distinct markers for estimating cognitive and kinematic NMDAR-gated specificity acting in the pre-frontal cortex while maintaining specificity among the GABA circuit of drugs in general circulation.