LOCALIZATION OF CCK RECEPTORS IN THALAMIC RETICULAR NEURONS - A MODELING STUDY

In an earlier experimental study, intracellular recording suggested th at cholecystokinin (CCK) suppresses a K+ conductance in thalamic retic ular (RE) neurons, yet the reversal potential of the CCK response, rev ealed using voltage clamp, was hyperpolarized significantly relative t o the KC equilibrium potential. Here, biophysical models of RE neurons were developed and used to test whether suppression of the K+ conduct ance, g(K), can account for the CCK response observed in vitro and als o to determine the likely site of CCK receptors on RE neurons. Suppres sion of g(K) in model RE neurons can reproduce the relatively hyperpol arized reversal potential of CCK responses found using voltage clamp i f the voltage clamp becomes less effective at hyperpolarized potential s. Three factors would reduce voltage-clamp effectiveness in this mode l the nonnegligible series resistance of the voltage-clamp electrode, a hyperpolarization-activated mixed cation current (I-h) in RE neurons , and the dendritic location of CCK-sensitive K+ channels. Although su ppression of g(K) in the dendritic compartments of model RE neurons si mulates both the magnitude and reversal potential of the CCK response, suppression of g(K) in just the somatic compartment of model RE neuro ns fails to do so. Thus the model predicts that CCK should effectively suppress K+ conductance RE neuron dendrites and thereby regulate burs t firing in RE neurons. This may explain the potent effects of CCK on intrathalamic oscillations in vitro.