Identification of dorsal–ventral hippocampal differentiation in neonatal rats

Abstract

The adult hippocampal formation (HF) is functionally, connectionally, and transcriptionally differentiated along the dorsal-ventral axis. At birth, the hippocampus appears shortened along its dorsal-ventral axis. We therefore questioned at what postnatal age the differentiated dorsal-ventral hippocampus is present. We first established that the ventral tissue in the short postnatal hippocampus remains ventral in the adult-like hippocampus. Second, using anatomical tracing techniques we report that, within the first postnatal week, the main input from the entorhinal cortex (EC) to HF is topographically organized. The terminal distribution of this input along the dorsal-ventral axis of HF was related to a dorsolateral-to-ventromedial axis of origin in EC, thus reflecting adult topography. Finally, we examined gene expression along the dorsal-ventral axis in the developing hippocampus. We found that several genes that were differentially enriched in the adult dorsal and ventral hippocampus were similarly enriched in the dorsal and ventral hippocampal poles at birth. The differentially expressed genes relate to different molecular pathways and biomarkers of disease. Taken together, these data lead us to conclude that the entire dorsal-ventral axis of HF is present at birth showing adult-like functional differentiation. Moreover, our findings indicate that the neonatal ventral hippocampus is enriched with biomarkers associated with mental illnesses. These include schizophrenia, affective and anxiety disorders, disorders previously deemed as ventral hippocampal associated disorders, as well as alcoholism. Our results thus suggest an early developmental susceptibility of the ventral HF to mental illness.

A molecular gradient along the longitudinal axis of the human hippocampus informs large-scale behavioral systems

“…Many of the genes identified in our study have also been described in previous studies characterizing the dorsal and ventral subdivisions and longitudinal gradients of the rodent hippocampus (e.g. [31, 51, 29, 46, 15]). This suggests a fair degree of homology between rodents and human in the distribution of proteins along the longitudinal axis of the hippocampus, and perhaps in the development and maintenance of the axis itself.…”

“…With this concept in mind, several studies have explored the molecular properties regulating the longitudinal axis of the hippocampus. A number of studies have characterized the genomic anatomy of the ventral-dorsal axis of the rodent hippocampus as a whole or across specific subfields [13, 15, 19, 31, 51], how gene expression along the axis changes over the course of development [29, 46], and how it influences patterns of connectivity [8]. While some consensus over implicated genes has been met, all of these studies have been performed exclusively in rodents, and it is unclear whether similar genes and proteins are responsible for regulating and characterizing the anterior-posterior axis of the human hippocampus.…”

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

“…The hippocampus is a heterogeneous structure with differences along the dorsal-ventral hippocampal axis in terms of function, gene expression, and neurotransmission (reviewed in [63]). The dorsal-ventral axis of the hippocampus is present even at day of birth [64] although its function is best understood in the adult brain. Generally, dorsal hippocampus is associated with learning and spatial navigation, and the ventral hippocampus is associated with stress regulation and affective behavior (reviewed in [63]).…”

The marked diversity of unique cortical enhancers enables neuron-specific tools by Enhancer-Driven Gene Expression

“…The brains were removed and horizontal or coronal 500 µm sections were cut on a Leica VT 1000 S microtome and kept at 4 °C until dissection. Bilateral dissection was performed, while watching the tissue through a dissection microscope with transmitted and reflected white light (Zeiss Discovery V8 stereomicroscope) applying architectonic criteria (Boccara et al, 2015;Jones and Witter, 2007;O'Reilly et al, 2015;Sugar and Witter, 2016;Witter, 2011) to unstained tissue. The tissue samples were snap-frozen in liquid nitrogen, kept at -80 0 C and shipped on dry ice.…”