The dentate gyrus (DG) of the ventral hippocampus is a key hub critical for the responses to prolonged chronic stress and antidepressant drugs, including the antidepressant candidate acetyl-L-carnitine (LAC). Prior studies from our and other laboratories showed transcriptome-wide signatures in this brain area with robust changes in genes important for neuronal plasticity, including the metabotropic glutamate receptor-2 (mGlu2), and insulin signaling pathways after chronic stress, and that these changes are ameliorated by short-term administration of LAC. Here, we used 10X Genomics droplet-based technology for Single Cell RNAseq (scRNAseq) assays to map the effects of chronic stress and antidepressant drugs of interest on each cell type of the ventral DG and the connected sub-areas of the ventral hippocampus. Our preliminary data showed a consistent dissociation of single nuclei from the ventral hippocampus as shown by the integrity of nuclei as well as the absence of nuclear aggregates and cellular debris. Next, we used 10x Genomics Chromium Controller System and Illumina Novaseq6000 to achieve sequencing depth of 37300 reads/nucleus from a total of 10411 nuclei/sample, with high-quality reads (95% of reads with quality>= Q30). Advanced bioinformatic analysis showed ~20 distinct cell-type clusters based on their expression patterns. Ongoing experiments are aimed at identifying gene expression profiles of specific cells that are known targets of chronic stress and antidepressant drugs. The single-cell approach here serves as a model to identify new markers and underlying mechanisms of brain plasticity and antidepressant response that may be important to translational research.