#	Pagina
attuale pagina	/open-h2020/projects/212736/results.html
-1	/open-h2020/projects/200193/results.html
-2	/open-dormire/toscana/MS/id-17516/stefanella.html
-3	/open-dichiarazioni/2012/82008/index.html
-4	/open-h2020/per-topic/centrepiece/list/index.html
-5	/open-ted/ita/tender/2022/nuts/dea31/all-all/index.html
-6	/open-h2020/per-topic/genommed/list/index.html
-7	/open-ted/ita/tender/2022/nuts/deb22/all-all/index.html
-8	/open-h2020/per-topic/90th/list/index.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MEMCIRCUIT (Deconstruction of a neural circuit for working memory: hubs, coding mechanisms, and signal routing)

Teaser

Summary

Working memory is the basis of cognition. It allows behaviour to be governed by internal goals rather than by reflexive stimulus-response mappings. The neural mechanisms of memory maintenance are heavily contested. Animal electrophysiology studies suggest a pivotal role of persistent spiking activity in single neurons of the prefrontal cortex, whereas human neuroimaging points to sub-threshold synaptic activity distributed across sensory cortex. This double dissociation of storage mechanisms and storage sites could result from the comparison of different recording methods, which measure distinct neuronal signals. Alternatively, there might be a fundamental difference between humans and animals. The key objective of this project is to formulate general principles of working memory coding at the cellular and circuit level by integrating across previously disconnected lines of research. We will address two central questions. First, where and how is the memorized information stored? We will use an innovative approach to record large-scale single-unit activity from a cognitive (prefrontal) and a sensory (auditory) region in awake neurosurgical patients and directly compare the data to recordings from mice performing the same auditory working memory task. This will allow us to determine whether the mnemonic fingerprints are species-specific or shared across humans and rodents. Second, what neural pathways support the flow of information during working memory? Using the animal model, we will disrupt cross-regional interactions in the memory network with millisecond-precise, projection-specific optogenetic tools in order to dissect the contribution of each hub to memory storage and memory access. This project provides an unprecedented one-to-one matching of behavioural tasks and recording methods with single-cell and split-second resolution in humans and rodents. It represents a major step forward in understanding the cellular and circuit basis of a critical cognitive brain function.

Work performed

For the mouse experiments, we have built high-throughput behavioural setups for training large groups of animals. We developed several variations of a working memory task with auditory stimuli to determine the most efficient training protocol for our mice. We are in the process of refining these protocols, but have already been able to successfully train the first animals on a sophisticated working memory task. We are also currently mapping the local and long-range circuits connecting the brain areas in the frontal and temporal lobes that are associated with processing the information needed to complete such a complex cognitive task. Ongoing work also includes implementing and testing equipment for electrophysiological and optical measurements of neuronal activity in trained animals.
For the human experiments, we have set up the intraoperative equipment required for simultaneous recording of behavioural responses and large-scale electrophysiological brain activity in awake neurosurgical patients. With adequate training on a working memory task prior to the surgery, we have found that our patients reach good to excellent intraoperative performance levels. We are currently in the process of collecting a full data set to investigate the neuronal signatures associated with representing and memorising sensory inputs in the human frontoparietal cortex.

Final results

By the end of the project, we expect to have a more detailed understanding of the cellular and circuit mechanisms that underlie our ability to maintain behaviourally information in online in working memory.