Local circuit GABAergic interneurons comprise the most diverse cell populations of
neuronal networks. Interneurons have been characterized and categorized based on their
axo-somato-dendritic morphologies, neurochemical content, intrinsic electrical properties
and their firing in relation to in-vivo population activity. Great advances in our
understanding of their roles have been facilitated by their selective identification.
Recently, we have described three major subtypes of deep short-axon cells (dSACs)
of the main olfactory bulb (MOB) based on their axo-dendritic distributions and synaptic
connectivity. Here, we investigated whether dSACs also display pronounced molecular
diversity and whether distinct dSAC subtypes selectively express certain molecules.
Multiple immunofluorescent labeling revealed that the most commonly used molecular
markers of dSACs (e.g. vasoactive intestinal polypeptide, calbindin and nitric oxide
synthase) label only very small subpopulations (< 7%). In contrast, voltage-gated
potassium channel subunits Kv2.1, Kv3.1b, Kv4.3 and the GABA(A) receptor alpha1 subunit
are present in 70-95% of dSACs without showing any dSAC subtype-selective expression.
However, metabotropic glutamate receptor type 1alpha mainly labels dSACs that project
to the glomerular layer (GL-dSAC subtype) and comprise approximately 20% of the total
dSAC population. Analysing these molecular markers with stereological methods, we
estimated the total number of dSACs in the entire MOB to be approximately 13 500,
which is around a quarter of the number of mitral cells. Our results demonstrate a
large molecular heterogeneity of dSACs and reveal a unique neurochemical marker for
one dSAC subtype. Based on our results, dSAC subtype-specific genetic modifications
will allow us to decipher the role of GL-dSACs in shaping the dynamic activity of
the MOB network.
