Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets

• Published in: Neurobiology of disease 2023-06, Vol.181, p.106094-106094, Article 106094
• Main Authors: Lindquist, Britta E., Timbie, Clare, Voskobiynyk, Yuliya, Paz, Jeanne T.
• Format: Article
• Language: English
• Subjects: Absence epilepsy; Burst firing; Epilepsy, Absence; Epilepsy, Generalized - therapy; Generalized spike-and-wave discharge; Genetic generalized epilepsy; Humans; Idiopathic generalized epilepsy; Oscillation; Seizures; Thalamus
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2023.106094

Generalized epilepsy affects 24 million people globally; at least 25% of cases remain medically refractory. The thalamus, with widespread connections throughout the brain, plays a critical role in generalized epilepsy. The intrinsic properties of thalamic neurons and the synaptic connections between populations of neurons in the nucleus reticularis thalami and thalamocortical relay nuclei help generate different firing patterns that influence brain states. In particular, transitions from tonic firing to highly synchronized burst firing mode in thalamic neurons can cause seizures that rapidly generalize and cause altered awareness and unconsciousness. Here, we review the most recent advances in our understanding of how thalamic activity is regulated and discuss the gaps in our understanding of the mechanisms of generalized epilepsy syndromes. Elucidating the role of the thalamus in generalized epilepsy syndromes may lead to new opportunities to better treat pharmaco-resistant generalized epilepsy by thalamic modulation and dietary therapy. •Generalized epilepsies impact children and adults and can be refractory.•Circuit specializations in thalamocortical neurons underlie physiologic rhythms.•Thalamocortical neuron function is disrupted in spike-and-wave discharges.•Thalamocortical circuits are an emerging therapeutic target in generalized epilepsy.