Lysergic acid diethylamide differentially modulates the reticular thalamus, mediodorsal thalamus, and infralimbic prefrontal cortex An in vivo electrophysiology study in male mice.
The reticular thalamus gates thalamocortical information flow via finely tuned inhibition of thalamocortical cells in the mediodorsal thalamus. Brain imaging studies in humans show that the psychedelic lysergic acid diethylamide (LSD) modulates activity and connectivity within the cortico-striato-thalamo-cortical (CSTC) circuit, altering consciousness. However, the electrophysiological effects of LSD on the neurons in these brain areas remain elusive. We employed in vivo extracellular single-unit recordings in anesthetized adult male mice to investigate the dose-response effects of cumulative LSD doses (5-160 µgkg, intraperitoneal) upon reticular thalamus GABAergic neurons, thalamocortical relay neurons of the mediodorsal thalamus, and pyramidal neurons of the infralimbic prefrontal cortex. LSD decreased spontaneous firing and burst-firing activity in 50% of the recorded reticular thalamus neurons in a dose-response fashion starting at 10 µgkg. Another population of neurons (50%) increased firing and burst-firing activity starting at 40 µgkg. This modulation was accompanied by an increase in firing and burst-firing activity of thalamocortical neurons in the mediodorsal thalamus. On the contrary, LSD excited infralimbic prefrontal cortex pyramidal neurons only at the highest dose tested (160 µgkg). The dopamine D2 receptor (D LSD modulates firing and burst-firing activity of reticular thalamus neurons and disinhibits mediodorsal thalamus relay neurons at least partially in a D