Dataset Information

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures.

ABSTRACT: There is a large unmet need for improved treatment for temporal lobe epilepsy (TLE); circuit-specific manipulation that disrupts the initiation and propagation of seizures is promising in this regard. The midline thalamus, including the mediodorsal nucleus (MD) is a critical distributor of seizure activity, but its afferent and efferent pathways that mediate seizure activity are unknown. Here, we used chemogenetics to silence input and output projections of the MD to discrete regions of the frontal cortex in the kindling model of TLE in rats. Chemogenetic inhibition of the projection from the amygdala to the MD abolished seizures, an effect that was replicated using optogenetic inhibition. Chemogenetic inhibition of projections from the MD to the prelimbic cortex likewise abolished seizures. By contrast, inhibition of projections from the MD to other frontal regions produced partial (orbitofrontal cortex, infralimbic cortex) or no (cingulate, insular cortex) attenuation of behavioral or electrographic seizure activity. These results highlight the particular importance of projections from MD to prelimbic cortex in the propagation of amygdala-kindled seizures.

SUBMITTER: Wicker E

PROVIDER: S-EPMC9361177 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures.

Wicker Evan E Hyder Safwan K SK Forcelli Patrick A PA

Progress in neurobiology 20220512

There is a large unmet need for improved treatment for temporal lobe epilepsy (TLE); circuit-specific manipulation that disrupts the initiation and propagation of seizures is promising in this regard. The midline thalamus, including the mediodorsal nucleus (MD) is a critical distributor of seizure activity, but its afferent and efferent pathways that mediate seizure activity are unknown. Here, we used chemogenetics to silence input and output projections of the MD to discrete regions of the fron ...[more]

PMID: 35537572

Similar Datasets

Project description:BackgroundThe 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.MethodsWe employed in vivo extracellular single-unit recordings in anesthetized adult male mice to investigate the dose-response effects of cumulative LSD doses (5-160 µg/kg, intraperitoneal) upon reticular thalamus GABAergic neurons, thalamocortical relay neurons of the mediodorsal thalamus, and pyramidal neurons of the infralimbic prefrontal cortex.ResultsLSD decreased spontaneous firing and burst-firing activity in 50% of the recorded reticular thalamus neurons in a dose-response fashion starting at 10 µg/kg. Another population of neurons (50%) increased firing and burst-firing activity starting at 40 µg/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 µg/kg). The dopamine D2 receptor (D2) 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.ConclusionLSD modulates firing and burst-firing activity of reticular thalamus neurons and disinhibits mediodorsal thalamus relay neurons at least partially in a D2-mediated fashion. These effects of LSD on thalamocortical gating could explain its consciousness-altering effects in humans.

Dataset Information

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures.

Publications

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets