Theoretical Neuroscience Podcast

A bursting neuron can maintain its firing-pattern identity throughout an animal's life, even though the ion-channel proteins underlying this identity are turned over on the timescale of days. Today's guest has proposed that neuronal identities are stored in the specific protein production rules, which are regulated by intracellular calcium signaling. And how can animals reliably perform a learned task for weeks, even when the underlying neural representation drifts over time, so-called representational drift?

Synaptic plasticity underlies several key brain functions including learning, information filtering and homeostatic regulation of overall neural activity. While several mathematical rules have been developed for plasticity both at excitatory and inhibitory synapses, it has been difficult to make such rules co-exist in network models. Recently the group of the guest has explored how co-dependent plasticity rules can remedy the situation and, for example, assure that long-term memories can be stored in excitatory synapses while inhibitory synapses assure long-term stability.

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?

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 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.

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.

In September Paul Middlebrooks, the producer of the podcast BrainInspired, and I were both on a neuro-AI workshop on a coast liner cruising the Norwegian fjords. We decided to make two joint podcasts with some of the participants where we discuss the role of AI in neuroscience. In this second part we discuss the topic with Cristina Savin and Tim Vogels and round off with a brief discussion with Mikkel Lepperød, the main organizer of the workshop, about what he learned from the workshop.

Most of what we have learned about the functioning of the living brain has come from extracellular electrical recordings, like the measurement of spikes, LFP, ECoG and EEG signals. And most analysis of these recordings has been statistical, looking for correlations between the recorded signals and what the animal/human is doing or being exposed to. However, starting with the neuron rather than the data, these electrical brain signals can also be computed from biophysics-based forward models, and this is topic of this podcast.