Lysergic acid diethylamide differentially modulates the reticular thalamus, mediodorsal thalamus, and infralimbic prefrontal cortex: An in vivo electrophysiology study in male mice

Background: 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. Methods: 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 mu g/kg, intraperitoneal) upon reticular thalamus GABAergic neurons, thalamocortical relay neurons of the mediodorsal thalamus, and pyramidal neurons of the infralimbic prefrontal cortex. Results: LSD decreased spontaneous firing and burst-firing activity in 50% of the recorded reticular thalamus neurons in a dose-response fashion starting at 10 mu g/kg. Another population of neurons (50%) increased firing and burst-firing activity starting at 40 mu g/kg. 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 mu g/kg). The dopamine D2 receptor (D-2) antagonist haloperidol administered after LSD increased burst-firing activity in the reticular thalamus neurons inhibited by LSD, decreased firing and burst-firing activity in the mediodorsal thalamus, and showed a trend towards further increasing the firing activity of neurons of the infralimbic prefrontal cortex. Conclusion: LSD modulates firing and burst-firing activity of reticular thalamus neurons and disinhibits mediodorsal thalamus relay neurons at least partially in a D-2-mediated fashion. These effects of LSD on thalamocortical gating could explain its consciousness-altering effects in humans.

Automated summary

The study investigates the effects of cumulative LSD doses on different neurons in the brain using in vivo extracellular single-unit recordings in adult male mice. LSD modulates firing and burst-firing activity of reticular thalamus neurons in a dose-response fashion, affecting thalamocortical relay neurons and pyramidal neurons in the prefrontal cortex. The D2 receptor antagonist haloperidol partially reverses the effects of LSD, suggesting a D-2-mediated mechanism for the modulation of thalamocortical gating.