Day 3: The Profound Differences Between Life With and Without a Cortex: Florian Engert, Gilles Laurent, Nuno da Costa, and Henry Kennedy

Synaptic Tempests: Beyond the Cortical Veil 

with Florian Engert, Gilles Laurent, Nuno da Costa, and Henry Kennedy

Author: Shreya Kshirasagar

Welcome and quick update on today's weather.

Why do you think I don't need an umbrella or a coat today? Well, its a bright sunny day with temperate air. 18-19°C as per reports. 

Not bad to tag along your favorite UV-blocking sunglasses. Don't compromise on your style or safety - choose the best for your vision today. 

On the side note: diurnal animals have evolved to specialized adaptations in order to naturally protect their retinas from harmful ultraviolet radiation. Snowy owls are a great example of delaying the release of toxic all-trans retinal, a molecule that can damage photoreceptor cells, in the retina. Think about what are the conditions that the snowy owl has to survive. Imagine a snowy owl with sunglasses, that'd be strikingly obnoxious like their eyes that most certainly command attention and inspire awe. 

Giacomo opened the floor for today. We have Florian Engert, Gilles Laurent, Nuno da Costa, and Henry Kennedy as speakers lined up for today's session to delve deeper into cortical circuits. 

Side note: Quick announcement about t-shirts for CapoCaccia participants. A lot of DG/WG lined up for the afternoon. Breaks at 1800, for sport/fitness/health are heavily encouraged. 

We have Andre van Schaik as our moderator. 

Melika Payvand was the new joinee for today.

Florian shapes our morning with animal behavior without cortex. He will talk instead of Markus Meister and  try to recess cortex for next 40 minutes. 

Florian Engert - What is life without cortex? 

Henry Kennedy took the floor – cortex in humans, the evolutionary process linked to it. 

Evolutionary development of the cortex. Lets look at the evolution from an emergence of complexity viewpoint. The cerebral cortex evolved as a key innovation in vertebrates, particularly mammals, enabling advanced sensory integration, motor control, and cognitive flexibility. Its expansion correlates with adaptive advantages such as problem-solving, social behavior, and environmental adaptability (e.g., primates, cetaceans, and corvids). 

Brains have evolved to solve problems in a pre-historic context…reference to 4 Fs from yesterday’s session. Have a look again! 

The hypothalamus is a small but critical brain region responsible for regulating vital physiological processes, including hormone release, autonomic functions, and behaviors like hunger, thirst, and emotional responses. Oxytocin is one of the key hormones produced in the hypothalamus, with wide-ranging roles in both the body and brain. Here's a breakdown: 

Image of 7 deadly sins and relation to hormones produced in the hypothalamus, this is an elusive interpretation created by Florian Engert.

Mice mating, 21 days later they stop killing babies and be good father. Neurons that turn on 21 days after mating. Splash of the news a couple of years ago, maybe NEW YORK TIMES?, you could ask Florian about it. 

Vijay Balasubramanian questions about space of level of molecules, to which Florian explains that there is a balance to the spatial distribution of the axis of these molecules.

Decision is done by sub-cortical circuits. However, one may ask, what is cortex good for? In this context, Florian expresses and tries to channelize the thoughts of his co-fellow, read below. 

Markus Meister’s postdoc at Harvard investigated rat's innate behavior of storing reward-based association. 700 ms to get the recording to understand the rat’s behavior to pushing the lever twice, with this delay. The repeated dance of the rats to elaborate the sequence of behaviors was in a way defining the role of cortex. This experiment led to their conclusion that cortex could be of less use with cognitive control abilities. For learning out of context, we need cortex. Once learnt, it is downloaded by sub-cortical circuits leaving cortex not so useful. Sub-cortical models are learning, adapting, they are entirely model-free. They predict, compute. Every animal comes pre-loaded with innate motor /problem solving they come with innate model, through their specialized evolutionary process. 

Susan Stepney questioned about the novelty of these evolutionary canonical circuits. Every system has feedback nested down to the nerve systems.

Constant crosstalk between cortex and sub-cortical leads to ripple effect. Cortex is the ultimate control system.

Cortical lesion or blindness doesn’t necessarily mean they can’t perform an action like catching a baseball.  This could a problem of the cortex. This could raise eyebrows and questions about visual cortical led inability in terms of perception. 40 years ago, a similar study was performed, but it was rudimentary. Henry Kennedy raised these questions. This was sort of heated debate. I leave it there. Whoever was in the room, witnessed it.

Do we need external instruction/patterned /instructive information? Or maybe it is gene based. I know this statement is vague, but hey all of this knowledge is quite tough, as I feel the pain in my upper thighs because of Yoga/Pilates the other evening, it was a refreshing swim post Yoga though. I will get better sleep for next sessions, bare with me dear readers. 

Esteban Real raised the questions of cortex less children and the generalization to the cortical led developments in mice. How far has the study gone? Florian's message to the question was 'What evolution did without cortex' ..they would provide with a counter argument on Friday. Don’t forget to join in. 

Gilles Laurent continued the session after an interruption, a necessary one by Andre v. Schaik. Muto-genesis may have been selected in the process of natural selection. We now delve into proteins and gene. Proteins control the expression of the genes. 

In the context of the topic raised about epigenetics by Gilles, Florian picked a nice thought on 'size of octopus'. Size of octopus, it has half a billion neurons, much smaller than size of the mice brain. He claims nothing really magical about cortex. Cerebral cortex topic was sort of drifted and we moved to discussions about connectivity, single cell embryology, migration of cells intra region.

    Nuno da Costa delving deep into synaptic relations to cortical neurons.

Henry Kennedy starts his talk.

Evolution of circuits and evolution of behaviors. He talked about why human brain has circuits at all. including visual systems and primary cortical systems. 

Henry collaborated with Pascal Firz, a rare electrophysiologist. EEG related - functional and structural hierarchy Predictive brain could be understood with coding. If you look at the global connectivity of the top-down approach; bottom-up are predicting errors. Object the notion of Florian asks why is there a problem with that? Canonical models of prediction.

                                        Henry Kennedy is at the center, delivering his talk 

Rodney Douglas and Kevin Martin's paper was referenced. They were claiming, specificity of loop

Henry continued what is important from a mammalian cortical perspective. Bottom-up connections seem obvious to Henry, but what is contextual information. 

Anatomical connectivity provides stable structural insights, while functional data (e.g., electrophysiology) is context dependent. Combining these approaches is essential to link structure to behavior or computational roles.

Predictive coding models propose that top-down connections convey predictions, while bottom-up signals relay prediction errors. However, the functional mechanisms of feedback connections remain unclear.

Excitatory and inhibitory neurons form specific, dedicated circuits. Inhibitory cells (e.g., basket cells) preferentially target distinct excitatory neuron types, suggesting highly specialized connectivity patterns.

Transcriptomic data (gene expression) alone may not fully explain functional roles, as similar cell types might serve different purposes. Integrating morphology, physiology, and molecular data is critical for accurate classification.

Some of the main points from today’s talk are summarized here:

•    The visual cortex is discussed as a model system, with debates about hierarchical organization. Feedback connections (top-down) are more abundant than feedforward, challenging traditional serial processing models.
•     Predictive coding emphasizes contextual modulation (e.g., occlusion experiments), where prior knowledge shapes perception. However, reconciling this with anatomical data (e.g., layer-specific connectivity) remains unresolved.
•     Non-human primates (e.g., macaques) are critical for studying human-like vision and cognition, but ethical concerns limit invasive research. Mouse models, while tractable, lack the complexity of primate systems.
•     Emerging tools like viral tracing, spatial transcriptomics, and single-cell technologies are highlighted for mapping cell-type-specific circuits and testing hypotheses.

We wrapped up the morning sessions. Everyone moved to lunch table for further extended discussions, some were brave enough to take the discussions to the sea with scorching sun. 

I spotted a few already taking the plunge to swim and snorkel. 

A lot of sessions lined up for discussions today. 

                                                    Creative use of sand as a white board. 

      

                                                       Beach Volleyball during sports break. 

 

      

      Most of us returned from tennis court, or a refreshing Yoga/Pilates session combined with cold water swim. Dinner tables are super fun, one could know the group, chew and chat. It really opens up different and diverse topics.

     

     This evening after dinner at 9pm, we discussed on the topic: 'Neuromorphic: the hype, the hope or the science'. The very questions we need to answer as a community. A lot of young neuromorphs took part in the discussion with their opinions, thoughts, ideas and did not hesitate to raise questions.

       Some snaps:

      Alright! that'll be all for today folks. See you tomorrow. 

 

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