Parallel frontal thalamo-cortical pathways in mice
Karola Költő1, 2, Aletta Magyar1, 3,Mónika Szabó1, 3, Anna Fehér1, Judit Berczik1, 3, Ofer Yizhar4, Ferenc Mátyás1, 5
The frontal thalamo-cortical system plays important roles in many cognitive processes. Any damage or dysfunction in this network can lead to neurological disorders like anxiety and schizophrenia. Although the large dataset regarding this system found in the literate, the precise anatomical organization between the involved medial thalamic and frontal cortical regions is missing. As the presence or absence of a calcium binding protein, the calretinin (CR) characterizes distinct medial thalamic populations (CR+, CR-negative), we used cell type- and target-specific approaches in Calb2(CR)-Cre mice to anatomically dissect the frontal thalamo-cortical system. CR+ and CR- thalamic neurons gave rise to a rather nonoverlapping axon arborizations in the cortex: while CR+ cells preferentially innervated prelimbic, infralimbic, orbital and insular cortices, CR- neurons sent axons to the cingulate and secondary cortical areas. The layer-specific distribution of their axonal inputs was also different in those cortical areas which were targeted by both populations. In addition, their subcortical projections were also distinct. While CR+ cells targeted limbic structures like ventral striatum, amygdala and ventral hippocampus/subiculum, CR- neurons avoided these regions. Besides that, distinct CR+ populations also showed some level of heterogeneity in their cortical and subcortical connectivity. For example, the amygdala- and the nucleus accumbens projecting medial thalamic cells innervated distinct domains of the bed nucleus stria terminalis and different layers of the frontal cortical regions, revealed by a retroanterograde viral approach. Altogether these findings indicate that the frontal thalamo-cortical system is organized in a complex manner by several parallel thalamic routes.