An emerging view of the hippocampus is that of a functionally heterogeneous structure along its longitudinal axis. Lesion studies reveal that the dorsal (septal pole) hippocampus is involved in learning and spatial memory, whereas the ventral (temporal pole) hippocampus regulates emotional and motivated behaviors (Fanselow and Dong, 2010). Anatomical connectivity and gene expression analyses support this functional dissociation. For example, serotonergic fibers provide denser input to the ventral hippocampus with a concomitant enrichment of 5-HT1A and 2C receptors ventrally (KF Tanaka and R Hen, unpublished). Efferent connectivity indicates that ventral hippocampus can modulate reward circuitry and emotional behavior through projections to nucleus accumbens, prefrontal cortex and amygdala, and stress responses by regulating the hypothalamic–pituitary–adrenal axis (Sahay and Hen, 2007). In both regions, the subgranular zone of the dentate gyrus (DG) continues to produce new neurons in adulthood. These adult-born granule cells (GCs) functionally integrate into the DG circuit, exhibit enhanced excitability, and have a significant impact on both learning and emotional behavior (Sahay and Hen, 2007). As adult neurogenesis has been implicated in both learning and mood, an exciting possibility is that adult-born GCs in the dorsal and ventral hippocampus may be functionally dissociated.

Chronic antidepressant treatment increases neurogenesis in the DG, a requirement for some of their behavioral effects (Santarelli et al, 2003). Recent studies suggest that antidepressants regulate behavior by selectively increasing ventral hippocampal neurogenesis. Chronic treatment with agomelatine, a melatonin receptor agonist, and 5-HT2C receptor antagonist with robust effects in animal models as well as efficacy in human major depressive disorder increases neurogenesis selectively in the ventral DG (Banasr et al, 2006). In humans, selective serotonin reuptake inhibitors and tricyclic antidepressants increase proliferating and neuronal precursor cells more prominently in the anterior portion of the DG of patients with MDD as compared to controls and untreated MDD subjects (Boldrini et al, 2009). These two studies, although correlational, provide exciting preliminary evidence that warrants future studies aimed at selectively blocking or stimulating neurogenesis in the ventral hippocampus.