Identification of Novel BDNF-Specific Corticostriatal Circuitries

Brain-derived neurotrophic factor (BDNF) is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF neurons in the corticostriatal circuitry. First, we used BDNF-Cre and Ribotag transgenic mouse lines to label BDNF-positive neurons in the cortex and detected BDNF expression in all the subregions of the prefrontal cortex (PFC). Next, we used a retrograde viral tracing strategy, in combination with BDNF-Cre knock-in mice, to map the cortical outputs of BDNF neurons in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We found that BDNF-expressing neurons located in the medial prefrontal cortex (mPFC) project mainly to the DMS, and those located in the primary and secondary motor cortices (M1 and M2, respectively) and agranular insular cortex (AI) project mainly to the DLS. In contrast, BDNF-expressing orbitofrontal cortical (OFC) neurons differentially target the dorsal striatum (DS) depending on their mediolateral and rostrocaudal location. Specifically, the DMS is mainly innervated by the medial and ventral part of the orbitofrontal cortex (MO and VO, respectively), whereas the DLS receives projections specifically from the lateral part of the OFC (LO). Together, our study uncovers previously unknown BDNF corticostriatal circuitries. These findings could have important implications for the role of BDNF signal-ing in corticostriatal pathways.Significance StatementBrain-derived neurotrophic factor (BDNF) is released in axons upon neuronal depolarization. Surprisingly, careful mapping of BDNF projecting neurons in the central nervous system (CNS) has not been conducted. Using retrograde viral strategies in combination with transgenic mice, we mapped out corticostriatal BDNF circuits. We found that, medial prefrontal cortex (mPFC) BDNF neurons project mainly to the dorsomedial striatum (DMS), whereas the motor cortex and insular cortex (AI) project to the dorsolateral striatum (DLS). BDNF neurons in the orbitofrontal cortical (OFC) are anatomically segregated. Whereas the DMS receives BDNF-positive projections from the VO, the DLS mainly receives BDNF-positive projections from the LO. Our findings could be important to the study of BDNF in corticostriatal circuitries.

Automated summary

This study characterized the distribution of brain-derived neurotrophic factor (BDNF) in the corticostriatal circuitry using transgenic mice and viral tracing techniques. It was found that BDNF is expressed in all subregions of the prefrontal cortex (PFC) and the connectivity of BDNF neurons with the striatum varies across different cortical regions.