Great insight created by tiny holes; celebrating 40 years of the brain micropunch technique

Forty years ago, a two page long article (without references) was published in Brain Research by Mikl？s Palkovits [1]. The article’s single figure show two coronal sections of the rat diencephalon with three tiny holes of thousand μm in diameter each; the first hole represented the removed paraventricular nucleus at the right side of the brain while the other two were of the habenular nuclei. The procedure - later named and officially known as brain micropunch method – helped to open a new chapter in neuroscience. As is case for many great scientific advances, Mikl？s Palkovits’ work occurred at the interfaces between two different disciplines. The first is classical neuroanatomy, a Hungarian “tradition” that started with Mihály Lenhossék, a contemporary and competitor of Santiago Ramón y Cajal who coined the name “astrocyte”. The tradition of excelling in neuroanatomy and neurohistology continued with János Szentágothai and Mikl？s Palkovits. The second discipline was neurochemistry. Improvements in analytical methods in the late ‘60s and early ‘70s increasingly enabled quantifying neurotransmitters, hormones, and metabolites from minute quantities of biological materials. Determining the concentrations of these and other molecules in the many functionally distinct brain regions promised a new level of understanding about complex biochemical and physiological processes of the central nervous system. Julius Axelrod pioneered work on how catecholamines, epinephrine, norepinephrine and dopamine—neurotransmitters of key neurological and psychiatric functions—are released and inactivated by reuptake. For this work, Julius Axelrod shared the Nobel Prize in Physiology or Medicine in 1970 with Bernard Katz and Ulf von Euler. It was Julius Axelrod who invited Miklos Palkovits to the National Institutes of Health (NIH) as “the guy who can dissect the suprachiasmatic nucleus” from the rat brain, the most important (if not the only) brain nucleus Julius Axelrod was interested in at the time. Axelrod’s invitation marked the beginning of an exceptionally fruitful collaboration between Mikl？s Palkovits and the Laboratory of Cell Biology (LCB) at the National Institute of Mental Health (NIH, Bethesda, Maryland). LCB was run by Michael Brownstein and it was a highly creative, intellectually stimulating and productive workplace. During his 6 month annual shifts at the NIH for ~30 years, Mikl？s Palkovits, in collaboration with neuroscientists and clinicians affiliated with various NIH laboratories, published dozens of papers in leading journals such as Nature, Science, and