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ActiveCortex
New insights into the perceptual process
Evidence suggests that the interaction of feed-forward and feedback information plays a key role in cognitive processing, helping to shape the way we experience the world. We spoke to Professor Matthew Larkum of the ActiveCortex project about his group’s work in testing a hypothesis for explaining the perceptual process
The first results from this ERC project suggest they have identified a powerful model for understanding the cerebral cortex. The crucial feature, says Professor Matthew Larkum, is an explosive ‘hot spot’ strategically located in the thin dendrites of the main neurons of the cerebral cortex. As unlikely as it may have seemed at first, their most recent data published in the journal Science show that they can alter perception by targeting this hot spot. “The cerebral cortex processes things like orientation, colour, shape and movement in different regions, which all have pyramidal neurons,” he explains.
Feed-forward information
Approximately 80 percent of the cortex is made up of these pyramidal cells, which stretch vertically across the layers of the cortex, and play an important role in processing information. Interestingly, the cortex conserves this architectural aspect everywhere, which Larkum interprets as meaning that understanding the role of pyramidal neurons is the key to unlocking the secrets of the cerebral cortex and therefore the basis of mammalian intelligence. The cortex is wired such that information from the outside world and internal information predominantly arrive at opposite ends of the pyramidal neurons. “For example, when seeing a tiger, your retina delivers the visual information that hits the bottom of your pyramidal neurons near the cell body, and causes them to fire in a steady, low-frequency way,” continues Professor Larkum.
On the other hand, if you just think about a tiger but don’t see it, then information from your internal representation of the tiger causes signals to be transmitted predominantly to the top of your pyramidal neurons. “If you had very strong thoughts about the tiger, you might even get a sporadic highfrequency response from these cells,” continues Professor Larkum.
However, what’s really special about these neurons is that they act like coincidence detectors and completely change their output when information arrives at both ends of the neurons
simultaneously. In this way, Larkum proposes, the pyramidal neuron is crucial for cognition because it acts as an associative device that draws together new information that relates to previously learned information. In other words, if you see an orange object move behind the green grass while in the wild, say, in
Chris Schwarz/Shutterstock India, you might suspect there’s a tiger, whereas the same orange color in the local park would not necessarily bring tigers to mind.
This ‘bringing to mind’, Larkum argues, is nothing other than putting the right contextual information to the end of the orange neurons and seeing if there’s a match. “In our latest study, we basically looked for calcium in the dendrites – the trigger for coincidence detection – and saw that it does in fact correlate with the moment of perception,” he says. “The clincher was that when we suppressed the coincidence detection mechanism in the dendrites, the animal no longer perceived anything at the same stimulus strength.”
This is very exciting because it suggests that higher brain function can be investigated and even manipulated by
We looked for calcium in the dendrites and saw that it does correlate with the threshold for perception. At the point where we know the rodent has recognised the object, we see calcium in the dendrites
focusing on this cellular switch. In another paper published in 2016, his team were able to show that transcranial magnetic stimulation suppresses this cellular switch, suggesting that it could be used as a non-invasive tool for investigating this mechanism in humans during cognitive tasks.
New info Context Context
New info Hot spot
How to see a tiger. New information from the retina or previous knowledge about tigers alone have only a subtle influence on neuronal firing, whereas the combination is dramatically different due to activation of a dendritic “hot spot”.
A basic feature of intelligent systems like the cerebral cortex is the ability to freely associate aspects of perceived experience with an internal representation of the world and make predictions about the future. We are interested in the computational power of single neurons and their contribution to cortical function. Our main hypothesis is that the extraordinary performance of the cortex derives from an associative mechanism built in at the cellular level to the basic neuronal unit of the cortex - the pyramidal cell (Larkum, Trends in Neurosciences, 2013). The mechanism is robustly triggered by coincident input to opposite poles of the neuron, is exquisitely matched to the large and fine scale architecture of the cortex and is tightly controlled by local microcircuits of inhibitory neurons targeting subcellular compartments. We are currently testing this hypothesis (“BAC firing”) on many levels using a variety of research techniques including multiple dendritic patch-clamp recordings in vitro, extracellular electrophysiological techniques, calcium imaging, somatic and dendritic patch-clamp recordings in vivo, two photon imaging (in vitro and in vivo), rodent behavioural experiments and optogenetic approaches.
Full Project Title
Active dendrites and cortical associations (ActiveCortex)
Project Objectives
The ActiveCortex research programme is dedicated to investigating the hypothesis that the extraordinary performance of the cortex derives from an associative mechanism built into the basic neuronal unit, the pyramidal cell. This hypothesis is being investigated within the programme at every level. Electrophysiological and optical techniques will be used to record and influence the intrinsic properties of cells in rodents, with both in vivo and in vitro experiments.
Project Funding
ERC-ADG-2014 - ERC Advanced Grant Total cost: EUR 2 386 303.75 EU contribution: EUR 2 386 303.75
Contact Details
Professor Matthew Larkum, Ph.D Humboldt University, Berlin Neurocure Cluster of Excellence
Laboratory address:
Neuroscience Research Center – Campus Mitte Charité Universitätsmedizin Berlin Charitéplatz 1 10117, Berlin, Germany T: +49 30 450 539 117 E: matthew.larkum@hu-berlin.de W: https://www.projekte.hu-berlin.de/en/larkum
Professor Matthew Larkum, Ph.D
Trends in Neurosciences Magazine. Cover design: Thomas Splettstoesser. An artist’s impression of a dendritic spike is shown in one of the pyramidal cells. Matthew Larkum, Ph.D is a Professor of Biology at Humboldt University of Berlin. His research group focuses on the processing of feedforward and feedback information in the cortex, and particularly on the contribution of active dendritic properties to the computational power of neocortical pyramidal neurons.
