Title : A new AAV tool specifically targeting Hippocampal CA2
Abstract:
Mice hippocampus contains three prominent subregions, CA1, CA3 and DG and is well regarded as an essential multiple task processor for learning, memory and cognition based on tremendous studies on these three subregions. The narrow region sandwiched between CA1 and CA3 called CA2 has been neglected for a long time. But it raises great attentions recently since this region manifests the indispensable role in social memory. Its unique physical position connecting CA1 and CA3 suggests the potential novel functions besides social memory regulation. But the CA2 is too small to be accurately targeted. A flexible AAV tool capable of accurately and efficiently targeting this region is highly demanded. To fill this gap, we generate an AAV expressing Cre driven by the Map3k15 promoter (AAV/M1-Cre) which can be easily utilized to help tracing and manipulating CA2 pyramidal neurons. Furthermore, M1-Cre successfully labeled a group of Map3k15+RGS14- pyramidal neurons that do not colocalize with any RGS14+/STEP+/PEP4+/Amigo2+ pyramidal neurons. These Map3k15+RGS14- pyramidal neurons have more complex spines than previously reported. They are probably the ones projecting to the revealed CA2 downstream targets, VMH, STHY and PMV in WT mice injecting this AAV/M1-Cre virus but not in Amigo2-Cre mice. Altogether, this tool provides a completely new, more flexible and extended strategy for in-depth CA2 functional study in the future.
Audience Take Away
- We successfully developed a CA2 specific Cre viral system (AAV/M1-Cre) to label and manipulate neural activity in CA2 region
- AAV/M1-Cre can efficiently drive CA2 pyramidal neurons as what Amigo2-cre transgenic mice does. Meanwhile, it even displayed an extraordinary CA2 targeting accuracy comparing to most of current available targeting systems for CA2 and it is much more flexible to be utilized into different mice to realize the CA2 specific manipulation and gene deletion
- We labeled a group of pyramidal neurons containing both Map3k15+RGS14- and Map3k15+RGS14+ neurons in Py layers of CA2
- Complex spine structures and highly diverse morphology of pyramidal neuron cell bodies can be observed not only in Map3k15+RGS14- neurons in CA2 Py layers, but also in Map3k15+RGS14+ or regular CA2 neurons in Py layer sometimes
