In WT mice is very strange and actually the difference in the picture is very big, also the size of the DG is bigger than expected compared to the rest of the smaller hippocampus; it should be shorter. If you are sure that the brains have been cutted properly and simmetrically than it worths to deepen.

Thank you Javier for your suggestion. I observed this in few mice which are heterozygous mutant but its in few mice not all. So definitely I need to check the references for mice line. Right now its just an observation of my own no conclusions.

In WT mice is very strange and actually the difference in the picture is very big, also the size of the DG is bigger than expected compared to the rest of the smaller hippocampus; it should be shorter. If you are sure that the brains have been cutted properly and simmetrically than it worths to deepen.

Thank you Paolo. I use vibratone for sectioning and collect all sections though  rostro-caudal axis in a symmetrical fashion. I have a series of sections showing difference from rostral to caudal.

If the difference is in all of the sections then the cutting plane is not straight, If the difference is in the hippocampus only, then it worths to be studied. Can you post pictures of sections before (rostrally) the hippocampus, let's say at the hypothalamus or PFC level ?

Pretty unusual to find this asymmetry in normal young animals (in my hands, maybe 1/500 show it) - not as unusual (but still unusual) in normal old animals (maybe 2-3/500). Have you observed seizure activity in these animals? This could be hippocampal sclerosis. In that case, the CA region (and subiculum) are killed and the DG is spared- possibly even increased. Look for astrogliosis (maybe with GFAP IHC) in the region formerly known as CA1.

Thank you so much Eric. I will try GFAP will update. I want to thank all the people who have given their valuable suggestions.

In most cases, this occurs when the brain was not oriented corrrectly during the freezing or when placed on the cryostat or microtome. Based on the picture submitted, it seems that the hemispheres are at different levels. Was the same thing observed for the lateral ventricles before you got to the hippocampus? I always check for assymetry when I cut.

In my experience, as already mentioned above, this happens mainly due to sectioning the brain asymmetrically. I saw that several times, even a very slight angle will lead to such differences between structures from different hemispheres.

What I used to do to circumvent this was to use a brain holder (for coronal sections), and symmetrically cut a small portion of the cerebellum. This way you have a higher chance to place the base of the brain very symmetrically in the vitratome prior to cutting.

Holder looks like these: ( https://www.wpiinc.com/products/physiology/rbma-200c-acrylic-brain-matrix-for-adult-mouse-coronal-slices-40-75g/ ).

Hope it helps!

Cheers

Thank you Lucas :)