Cellular models in neuroscience

master's thesis

• Title (croatian): Stanični modeli u neuroznanosti
• Author: Andrej Novak
• Mentor: Svjetlana Kalanj Bognar (mentor)
• Committee member: Svjetlana Kalanj Bognar (predsjednik povjerenstva)
• Committee member: Goran Sedmak (član povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-03-09, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience

Abstract

In 1952, Alan Hodgkin and Andrew Huxley produced one of the most prolific and significant
scientific paper in the history of physiology that was a result of their collaboration that
first started in 1939. Their research at the Physiological Laboratory in Cambridge and the
Marine Biological Association Laboratory in Plymouth oered key insights into nerve cell
excitability. Their legacy includes not only our knowledge of how voltage-gated ion channels
influence propagating action potentials, but also the framework for modelling and analyzing
ion channel kinetics as they managed to capture the random openings and closings
of a plethora of ion channels into just four macroscopic variables; the membrane voltage
and three gating variables - much like Fick’s law provides a macroscopic description of
chemical diusion in terms of concentration without explicitly considering the underlying
Brownian motion of myriad molecules. To this date, it remains one of the greatest illustrations
of how phenomenological description combined with mathematical modelling may
reveal processes long before they can be detected firsthand (for example by visualization).
Their work was awarded a Nobel Prize in Physiology or Medicine in 1963, and served as
a basis for numerous other Nobel Prize-winning work. The most notable examples are the
work of Erwin Neher and Bert Sakmann’s ”discoveries concerning the function of single
ion channels in cells” ( in 1976), and in 2003, Roderick MacKinnon’s ”structural and
mechanistic studies of ion channels”. One could argue that this was a starting point
for cellular neurophysiology - a broad subfield of neuroscience that studies neurons at the
cellular level. In this thesis, we will focus on their results, as well as on a number of dierent
models that arose from it and have sparked the creation of new and attractive research
directions of neural models. These types of models are increasingly recognized by both experimentalists
and theoreticians as they are opening unique multidisciplinary collaborative
research and educational opportunities.

Abstract (english)

Godine 1952. Alan Hodgkin i Andrew Huxley objavili su jedan od najznačajnijih znanstvenih
radova u povijesti fiziologije koji je bio rezultat njihove suradnje zapoˇcete ve´c 1939.
Njihovo istraživanje u Physiological Laboratory u Cambridgeu i Laboratoriju Marine Biological
Association Laboratorija u Plymouthu je ponudilo kljuˇcne uvide u pobudljivost
živčanih stanica. Njihovo nasljede ne uključuje samo naše znanje o tome kako naponski
vodeni ionski kanali utječu na propagaciju akcijskih potencijala, već i okvir za modeliranje
i analizu kinetike ionskih kanala budući da su nasumično otvaranje i zatvaranje mnoštva
ionskih kanala uspjeli modelirati samo s četiri makroskopske varijable; napon membrane i
tri varijable provodenja - što se može usporediti s Fickovim zakonom koji nudi makroskopski
opis difuzije u smislu koncentracije bez eksplicitnog razmatranja temeljnog Brownovog
gibanja bezbrojnih molekula. Njihov rad do danas ostaje jedna od najvećih ilustracija
kako fenomenološki opis u kombinaciji s matematičkim modeliranjem može otkriti procese
mnogo prije nego što se mogu opaziti npr. direktnom vizualizacijom. Njihov je rad
nagraden Nobelovom nagradom za fiziologiju i medicinu 1963. godine i poslužio je kao osnova
za brojne druge radove dobitnike Nobelove nagrade. Najznačajniji primjeri su radovi
Erwina Nehera i Berta Sakmanna ”otkrića funkcija pojedinačnih ionskih kanala u stanicama”
objavljenog 1976., te rad iz 2003., koji se bavi ”strukturnim i mehaničkim studijama
ionskih kanala” autora Rodericka MacKinnona. Moglo bi se tvrditi da je to bila
početna točka za stanićnu neurofiziologiju – široko podpolje neuroznanosti koje proučava
neurone na staničnoj razini. U ovom diplomskom radu usredotočit ćemo se na rezultate
Hodgkina i Huxleyija, kao i na niz različitih modela koji su iz njih proizašli te potaknuli
stvaranje novih i atraktivnih smjerova istraživanja modela neurona. Takvi modeli su sve
više prepoznati i od eksperimentalnih i teorijskih znanstvenika jer otvaraju mogućnosti za
jedinstvena multidisciplinarna istraživanja i studijske programe.

• Keywords: celluar models; neuroscience
• Keywords (english): stanični modeli; neuroznanost
• Language: english
• URN:NBN: urn:nbn:hr:105:664497
• Study programme: Title: Medicine (in English language); Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-12-21 12:14:38