To answer the question of sight-in, I zero for 100yds. This gives approx. 1" rise at 50yds, or hold on bottom of squirrel's head. Ditto for under 25yds, hold "on", for under 25yds, hold over. Hold over increases as range gets even closer.
For shots under ~20yds, I carry either a Ruger MkI that belonged to my older brother; or my S&W 6" 617.
I've had a .17hmr from nearly the beginning. (announced in Jan, bought in July, killed first squirrel on Aug 15 (first day of season), I believe it was '02.
Even with a head shot, you usually take most of the front shoulder with it!!!
For "edible" squirrels, leave the .17 at home.
I use a Multi-X type reticle and practice occasionally on closer in targets to get the "estimation" of hold over.
edited to add: 50years ArchAngel ??? How much lead is that??? not sure I could hit something at 50years....(kidding ya know!)