Thalamic T-Type Ca2+ Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex

Title
Thalamic T-Type Ca2+ Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex
Authors
김정진우정훈박영권채수진조선미최정우홍영준염영일박성훈김경환신희섭김대수
Issue Date
2011-03
Publisher
Journal of neuroscience
Citation
VOL 31, NO 11, 4063-4073
Abstract
Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the development of frontal lobe dysfunction, including frontal lobe-specific seizures and abnormal hyperactivity. Before the onset of these abnormalities, the cross talk between theMDand PFC nuclei at theta frequencies was enhanced. During the theta frequency interactions, burst spikes, known to depend on T-type Ca2 channels, were increased in MD neurons. In vivo knockout or knockdown of the T-type Ca2 channel gene (CaV3.1) in the MD substantially reduced the theta frequency MD–PFC cross talk, frontal lobe-specific seizures, and locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a hypoxic lesion in the PFC results in abnormal thalamocortical feedback driven by thalamic T-type Ca2 channels, which, in turn, leads to the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of neuropsychiatric disorders arising from irreversible PFC damage.
URI
http://pubs.kist.re.kr/handle/201004/41077
ISSN
0270-6474
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KIST Publication > Article
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