A future computational neuroscience project could be to model not only the signal processing properties of neurons, but also all processes that keep a neuron alive for, say, a 100-year life span.

In 2012 the group of the guest published the first such whole-cell model for a very simple bacterium (M. genitalia). In 2020 a model of the larger E. coli bacterium comprising 10.000 equations and 19.000 model parameters was presented.

How are such models built, and what can they do?

Numerous neuron models have been made, but most of them are "single-purpose" in that they are made to address a single scientific question. In contrast, multipurpose neuron models are made to be used to address many scientific questions.

In 2011, the guest published a multipurpose rodent pyramidal-cell model which has been actively used by the community ever since.

We talk about how such models are made, and how his group later built human neuron models to explore network dynamics in brains of depressed patients.

With modern electrical and optical measurement techniques, we can now measure neural activity in hundreds or thousands of neurons simultaneously. This allows for the investigation of population codes, that is, of how groups of neurons together encode information.

In 2019 today’s guest published a seminal paper with collaborators at UCL in London where analysis of optophysiological data from 10.000 neurons in mouse visual cortex revealed an intriguing population code balancing the needs for efficient and robust coding.

We discuss the paper and (towards the end) also how new AI tools may be a game-changer for neuroscience data analysis.

The observed variety of dendritic structures in the brains is striking. Why are they so different, and what determine the branching patterns?

Following the dictum “if you understand it, you can build it”, the lab of the guest builds dendritic structures in a computer and explore the underlying principles.

Two key principles seem to be to minimize (i) the overall length of dendrites and (ii) the path length from the synapses to the soma.

The term “foundation model” refers to machine learning models that are trained on vast datasets and can be applied to a wide range of situations. The large language model GPT-4 is an example.

The group of the guest has recently presented a foundation model for optophysiological responses in mouse visual cortex trained on recordings from 135.000 neurons in mice watching movies.

We discuss the design, validation, use of this and future neuroscience foundation models.

A holy grail of the multiscale approach for physical brain modelling is to link the different scales from molecules, via cells and local neural networks, up to whole-brain models.

The goal of the Virtual Brain Twin project, lead by today’s guest, is to use personalized human whole-brain models to aid clinicians in treating brain ailments.

The podcast discusses how such models are presently made using neural field models, starting with neuron population dynamics rather than molecular dynamics.

In 1982 John Hopfield published the paper "Neural networks and physical systems with emergent collective computational abilities" describing a simple network model functioning as an associative and content-addressable memory.

The paper started a new subfield in computational neuroscience and led to the influx of numerous theoretical scientists, in particular physicists, to the field.

The podcast guest wrote his PhD thesis on the model in the early 1990s, and we talk about the history and present impact of the model.

The leading theory for learning and memorization in the brain is that learning is provided by synaptic learning rules and memories stored in synaptic weights between neurons.

But this is for long-term memory. What about short-term, or working, memory where objects are kept in memory for only a few seconds?

The traditional theory held that here the mechanism is different, namely persistent firing of select neurons in areas such as prefrontal cortex. But this view is challenged by recent synapse-based models explored by today’s guest and others.