NS 666: (Drunk) History of Neuroscience
But, you know, not really drunk. It’s just a figure of speech (we gotta say that for the lawyers).
Week 1: 04/26/21
The Neuron Doctrine
Let’s ease in with the grandaddy of all controversies: the neuron doctrine. How did a fight for the ages between Golgi and Cajal build the foundation for 100+ years of neuroscience? And how could Golgi have been SO wrong?! Start at the link below and then see the PDFs for some perspectives for reading.
https://www.sciencedirect.com/topics/neuroscience/neuron-doctrine
Week 2: 05/03/21
Neuronal Outgrowth and Chemosensation
Let’s begin with early work that established cell culture to study neurons (yeah, science has US to thank for that!), debunked the syncytial theory of cells, established neuronal motility and outgrowth, and how we first started thinking about how chemistry and molecular interactions affected those processes!
Week 3: 05/17/21
Neurodevelopment, NGF, and Neural Patterning
How does a nervous system wire itself? How are neurons instructed to grow over long distances? How resilient is the nervous system to changes? Some fundamental work in developmental biology using tissue transplants and sarcomas revealed these pathways to scientists - starting in the 1930s with work by Viktor Hamburger and continued in the 1950s with work by Rita Levi-Montalcini. Stanley Cohen and Levi-Montalcini won the 1986 Nobel Prize for this work. This will expand on Harrison’s work from last time and talk about how nervous systems are fundamentally patterned!
Week 4: 06/02/21 (outside?!)
Concepts of the Action Potential
In the early 1950s, it was a dark time. We knew currents were a thing in neurons, but no one could really describe how they happened. Then, as fate would have it, Hodgkin and Huxley met a squid and the rest, as they say, is the action potential. This time, we’ll look at two papers: 1952b focuses on the depolarization and 1952c on the recovery after depolarization. If you want to learn about the method they used (this fancy new thing called a “voltage clamp” that too is below, but it’s for your own intrigue!
Week 5: 06/14/21
Circuit Development and Ocular Dominance
In the 1950s and the 1960s, we knew very little about sensory processing. How do cells process information? How is that read out by the brain? How are those signals transformed into information? At the center of this, surrounded by all else, were David Hubel and Torsten Wiesel. Their work (which won the Nobel Prize in 1981) represented a quantum step in how the visual system processes stimuli and how circuits develop in accordance with those functional requirements. We’ll examine their seminal 1962 paper with the original cat videos! If you’re adventurous, visit their 1959 work as well!
Week 6: 06/28/21
LTP, Spontaneous Transmission, and Calcium
By the late 1960s, we knew how to record but a number of things remained a mystery. How did transmission work? What role did Calcium play? How could you get both evoked and spontaneous transmission? And why was there variability in neuronal response, depending on when the terminal had last fired? We’ll read two landmark studies - first, Katz and Miledi finding that calcium induces neurotransmitter release and second, Bliss and Lomo on how nerve terminal responses potentiate, both identifying key biophysical concepts for our understanding of what would become learning and memory.
Week 7: 07/12/21
Synaptic Vesicle Fusion and Cycling
At the beginning of the 90s, owing to a vast amount of work in yeast from people like Peter Novick and Randy Schekman, we knew a bit about how things were secreted. But do the secretion mechanisms uncovered in yeast underlie the molecular events of neurotransmission? Can we achieve a molecular understanding of how neurotransmitter release, the action potential, minis, and LTP are achieved? This week, we’ll investigate two studies that focused on biophysics of vesicle fusion and the SNARE complex (Sollner et al.) and discovery of SNARE components (Geppert et al.) as landmark papers that brought us closer to an understanding of how secretion and neurotransmission overlap.
Week 8: 07/26/21
Molecular Axon Guidance, Attraction and RepulsiON
At the beginning of this extravaganza, we talked about how axons find their targets. For nearly 40 years, we knew they had to respond to cues, likely molecular, but those cues remained a mystery. But as the Berlin Wall fell, another revolution was happening. Tessier-Lavigne defined the source of these cues and work from Corey Goodman, Tessier-Lavigne, and Cori Bargmann linked specific genes to these cues. We’ll examine MTL’s initial findings and the first fly screen to mutate new genes like robo and commissureless.