Bidirectional modulation of fear extinction by mediodorsal thalamic firing in mice

Sukchan Lee, Touqeer Ahmed, Soojung Lee, Huisu Kim, Sukwoo Choi, Duk Soo Kim, Sang Jeong Kim, Jeiwon Cho, Hee Sup Shin

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60 Scopus citations


The mediodorsal thalamic nucleus has been implicated in the control of memory processes. However, the underlying neural mechanism remains unclear. Here we provide evidence for bidirectional modulation of fear extinction by the mediodorsal thalamic nucleus. Mice with a knockout or mediodorsal thalamic nucleusg-specific knockdown of phospholipase C Î 24 exhibited impaired fear extinction. Mutant mediodorsal thalamic nucleus neurons in slices showed enhanced burst firing accompanied by increased T-type Ca 2+ currents; blocking of T channels in vivo rescued the fear extinction. Tetrode recordings in freely moving mice revealed that, during extinction, the single-spike (tonic) frequency of mediodorsal thalamic nucleus neurons increased in wild-type mice, but was static in mutant mice. Furthermore, tonic-evoking microstimulations of the mediodorsal thalamic nucleus, contemporaneous with the extinction tones, rescued fear extinction in mutant mice and facilitated it in wild-type mice. In contrast, burst-evoking microstimulation suppressed extinction in wild-type mice, mimicking the mutation. These results suggest that the firing mode of the mediodorsal thalamic nucleus is critical for the modulation of fear extinction.

Original languageEnglish
Pages (from-to)308-314
Number of pages7
JournalNature Neuroscience
Issue number2
StatePublished - Feb 2012

Bibliographical note

Funding Information:
We thank J. Park for assistance with animal care and I. Hong for behavioral tests in the beginning of this work. This work was supported by a grant from the National Honor Scientist Program of Korea and a grant from the 21C Frontier Proteomics Program of the Ministry of Education, Science and Technology, Korea.


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