Thalamic T-Type Ca2+ Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex
- Thalamic T-Type Ca2+ Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex
- 김정진; 우정훈; 박영권; 채수진; 조선미; 최정우; 홍영준; 염영일; 박성훈; 김경환; 신희섭; 김대수
- Issue Date
- Journal of neuroscience
- VOL 31, NO 11, 4063-4073
- 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.
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