Brain Science with Ginger Campbell, MD

Episode 147: "Eve Marder's Life in Neuroscience" (ad-free)

August 15, 2018

Main Theme & Purpose

In this episode, Dr. Ginger Campbell provides a deep dive into the intellectual biography "Lessons from the Lobster: Eve Marder’s Work in Neuroscience" by Charlotte Nassim. Focusing on the groundbreaking career of neuroscientist Dr. Eve Marder, Campbell highlights the ways Marder’s discoveries have shaped contemporary neuroscience, particularly regarding neural variability, neuromodulation, and circuit function. The episode is intended as both an overview of Marder’s key scientific contributions and an inspiration for students and working scientists.

Key Discussion Points and Insights

About the Book (“Lessons from the Lobster”)

• Biography covers Eve Marder’s career via her scientific ideas rather than a traditional chronological approach.
• Nassim, the author, has a neuroscience background and based the book on access to lab notebooks, publications, direct interviews with Marder and her colleagues.
• The book is recommended for aspiring neuroscientists, as it captures the evolution of the field and theory through Marder’s career.
  • [03:10] Quote: "It's not an exaggeration to say that over her career, Marder has made several paradigm-shifting discoveries." – Dr. Ginger Campbell

Eve Marder’s Key Contributions to Neuroscience

Dr. Campbell lists and elaborates on the major discoveries:

1. Discovery about Neurotransmitters in Lobster Ganglia

   • Marder identified acetylcholine as the main neurotransmitter at the neuromuscular junction in the lobster’s stomatogastric ganglion, challenging the assumption it was glutamate.
   • Context: Work was done during her time as a graduate student in the 1970s when few neurotransmitters were known.
   • Findings published in Nature before her dissertation was completed.
     • [07:24] “In her very first publication, Marder challenged the status quo.” – Dr. Campbell

2. Caution in Extrapolating Results

   • Demonstrated the danger in generalizing findings even between closely-related species.

3. Seeing Value in Experimental ‘Errors’

   • Marder viewed apparent experimental noise as potentially insightful data, not just mistakes.

4. Pioneered Understanding of Neuromodulation

   • Established that neural circuits are not static; modulatory substances can modify neuronal activity without altering basic wiring or synaptic strength.
   • Early work resisted by the field; eventually recognized as foundational.
   • [18:45] “Neuromodulation meant that the interaction between neurons could change without changing their physical connections.” – Dr. Campbell

5. Exploration of Central Pattern Generators (CPGs)

   • Detailed the stomatogastric ganglion as a model for central pattern generation, showing these circuits are subject to multiple influences with significant variability.
   • No “one size fits all” model for CPGs; emphasized unique adaptations in different species.

6. Dynamic Clamp Technique

   • Collaboration with Larry Abbott led to the creation of the dynamic clamp—a major methodological advance allowing real neurons to be linked via electronic circuits, simulating diverse network scenarios.
     • Recognized as a Nobel-worthy development by Dr. Campbell.
     • [39:10] “In my opinion, this basic idea is Nobel Prize worthy because it's been used to generate new knowledge by many other researchers.” – Dr. Campbell

7. Principles of Neural Tuning and Targeting

   • Introduced the concept of ‘tuning to target’: neurons adjust their intrinsic properties (e.g., ion channel expression) to achieve required network outputs based on feedback.

8. Importance of Variability and Multiple Solutions

   • Demonstrated that neurons and networks can reach the same functional outcome through different underlying properties.
   • Noted that what was traditionally labeled ‘noise’ may be integral, reproducible biology.
     • [54:33] “Data that has previously been discarded as noise or error may actually be informative.” – Dr. Campbell

Additional Themes and Developments

Mentorship & Scientific Culture

• Marder credited for her generosity as a mentor and as someone who values collaboration and crediting others—a recurring motif shared in the book and podcast.
  • [14:10] “She unfailingly credits the creativity and insights of her students and colleagues.” – Dr. Campbell

Computational Modeling

• Marder’s early and ongoing embrace of computational neuroscience, using models to probe circuit behaviors beyond what wet-lab experiments could show.
• Dynamic clamp enabled hybrid experiments, greatly expanding the kinds of questions neuroscientists could ask.

The Pitfalls of Averaging Data

• Classic practice of averaging results can obscure biologically important variability—sometimes generating ‘average’ neurons that behave in ways no real neuron does.
  • [1:05:25] “Averaging can result in something that doesn't respond to anything that was in the population under study. Kind of sobering.” – Dr. Campbell

Facilitating Interdisciplinary Science

• Marder’s collaborations with theorists and physicists served as a model for effective interdisciplinary research, combining real data with robust modeling.

Notable Quotes & Memorable Moments

• [19:20] “Through a series of painstaking experiments, her lab established that different neurons could respond to the exact same stimulus in different ways.”
• [44:00] "She has a very deep abiding respect for the actual data, whether it comes out of an animal or a computer model."
• [55:40] "Marder's team... did new experiments that showed this same three- to five-fold range of variability. It seems to be highly reproducible because many other groups in other labs began to find this. It was like Marder said, it was there in the data if you looked." – Dr. Campbell

Timestamps for Important Segments

• 00:00–06:00 – Introduction, book background, methodology
• 06:00–15:00 – Early discoveries: neurotransmitter identity, extrapolation dangers
• 15:00–29:00 – Neuromodulation, early resistance, shifting paradigms
• 29:00–40:00 – CPGs, central pattern generators, network flexibility, contribution of Peter Getting
• 40:00–54:00 – Dynamic clamp, computational modeling, failures and successes of models
• 54:00–1:05:00 – Variability, 'tuning to target', the perils of averaging data
• 1:05:00–End – Implications for neuroscience, mentorship, summary of Marder’s legacy

Closing Reflections

• Dr. Campbell lauds Eve Marder for original thinking, scientific generosity, and for championing a nuanced, data-centered, mentorship-oriented approach to science.
• Recommends “Lessons from the Lobster” as essential reading for anyone interested in neuroscience.
• Stresses that Marder’s paradigm shifts—regarding variability, neuromodulation, and model circuits—will continue shaping the field for years to come.

Summary Table: Eve Marder’s Key Contributions

| Discovery/Insight | Impact | |--------------------------------------------|-------------------------------------------------------------------------------------| | Acetylcholine as lobster neurotransmitter | Overturned assumptions, careful experimental work | | Extrapolation caution | Cross-species differences must always be considered | | Value in ‘error’ and variability | Experimental ‘noise’ as source of discovery | | Neuromodulation in circuits | Redefined role of neurotransmitters/modulators | | Central pattern generator complexity | No universal wiring; unique evolutionary histories | | Dynamic clamp technique | Opened new experimental vistas, interdisciplinary collaboration | | Tuning to target | Feedback-based homeostatic regulation at circuit level | | Multiple valid solutions (variability) | No canonical ‘average’ neuron; plasticity and robustness are the rule, not exception |

Useful for Listeners

This summary offers a structured exploration through Eve Marder’s most important contributions as discussed by Dr. Campbell, providing insights into how neuroscientific thinking has shifted over the past 40+ years. Major themes include respect for real data, acknowledgment of biological variability, and a call to re-examine assumed dogmas—making Marder’s work essential for anyone interested in how science changes and how models and experiments intertwine.

For further reading, Dr. Campbell recommends “Lessons from the Lobster” by Charlotte Nassim and her prior interview episode with Dr. Eve Marder, now available for free on the Brain Science podcast feed.