Deep brain stimulation of the mediodorsal thalamic nucleus yields increases in the expression of zif-268 but not c-fos in the frontal cortex

• The brain regions activated by DBS of the MD nucleus are mapped.
• Differential zif-268 and c-fos expression may identify regions persistently, rather than transiently, activated.
• zif-268 induction highlights the frontal cortices as the structure activated.

This study explores the regions activated by deep brain stimulation of the mediodorsal thalamic nucleus through examination of immediate early genes as markers of neuronal activation. Stimulation was delivered unilaterally with constant current 100 μs duration pulses at a frequency of 130 Hz delivered at an amplitude of 200 μA for 3 h. Brains were removed, sectioned and radio-labelled for the IEGs zif-268 and c-fos. In anaesthetised rats, deep brain stimulation of mediodorsal thalamic nucleus produced robust increases in the expression of zif-268 but not c-fos localised to regions that are reciprocally connected with the mediodorsal thalamic nucleus, including the prelimbic and orbitofrontal cortices, and the premotor cortex indicating an increase in synaptic activity in these regions. These findings map those brain regions that are persistently, rather than transiently, activated by high frequency electrical stimulation of the mediodorsal thalamic nucleus by a putatively antidromic mechanism which may be relevant to neuropsychiatric disorders such as schizophrenia in which thalamocortical systems are disrupted and in which DBS protocols are being considered.