Medial Temporal Lobe and Prefrontal cortex connectivity as a neural resource for recognition memory 

B01

Recognizing objects, environments and people in the everyday life allows us to orient ourselves in a complex world. This ability differs between individuals and changes at different stages of life. Our goal is to understand how these differences are linked to neuronal networks within and between brain areas crucial for cognition: the medial temporal lobe (MTL) areas and the prefrontal cortex (PFC).

Principal Investigators

CRC 1436 member Matthias Prigge

Dr. Matthias Prigge

CRC 1436 member Magdalena Sauvage

Prof. Dr. Magdalena Sauvage

Dr. Matthias Prigge

Matthias Prigge did his Ph.D. in experimental biophysics in the lab of Peter Hegemann, where he worked on photoreceptors, and how to employ them to manipulate neuronal circuits. These proteins are now commonly used to manipulate neuronal circuits while models animals are performing a behavioral task. For his Postdoc, he joined the lab of Ofer Yizhar at the Weizmann Institute of Science in Israel. Here, he developed an interest in systems neuroscience and in particular, how to manipulate neuromodulatory networks to ease symptoms during progression of neurodegenerative disease. His lab is designing optical tools and technologies to better understand neuromodulatory networks in healt and disease.

Institut:Leibniz Institute for Neurobiology (LIN) Magdeburg

Project Title:B01 Medial temporal lobe and prefrontal cortex connectivity as a neural resource for recognition memory

Prof. Dr. Magdalena Sauvage

Magdalena Sauvage leads the Functional Architecture of Memory (FAM) department and co-directs the Leibniz Institute for Neurobiology (LIN) in Magdeburg. She gained expertise in memory function throughout her career at the MPI for Psychiatry (Munich, Germany), MIT (Graybiel lab, Boston, USA) and Boston University (Eichenbaum lab, USA). Her department investigates the neural basis of memory in health and pathology using human to rats translational tasks combined with high-resolution molecular imaging, optogenetics, single-cell in-vivo electrophysiology and 9.4T fMRI in awake rats. She organizes the biennal international and interdisciplinary FAM conference series, is member of the CRC1436 Steering Committee and serves as editor for “Neurobiology of Learning and Memory”.

Institut:Leibniz Institute for Neurobiology (LIN) Magdeburg

Project Title:B01 Medial temporal lobe and prefrontal cortex connectivity as a neural resource for recognition memory

Co-Workers

CRC 1436 member Erika Atucha

Dr. Erika Atucha

CRC 1436 member Julia Büscher

Julia Buescher

picture is coming soon

Liv Mahnke

picture is coming soon

Halla Mulla Osman

Dr. Erika Atucha

coming soon

Julia Buescher

I am a PhD student at the Leibniz Institute of Neurobiology and focused on behavioral neuroscience. Within the framework of project B01, I study how the network between hippocampus and prefrontal cortex influences the ability to recognize objects in dependence of their location. For this purpose, I am interested in interindividual differences in mice performing in an object-in-place task and examining the underlying differences in the neurocognitive circuit.

Liv Mahnke

coming soon

Halla Mulla Osman

coming soon

The MTL areas and the PFC are neuronal hubs for recognition memory

Damage to the MTL leads to severe memory deficits as seen for example in aging. The MTL includes the hippocampus (HIP), the entorhinal, the perirhinal, and the postrhinal cortices. The PFC is thought to recognize abstract connections between individual memories. We focus on how specific subsets of neurons of these brain regions are recruited into ‘engrams’ to support memory formation and serve memory retrieval, what is the relationship between these neuronal networks and how this relationship evolves with aging

What is an engram and how does it change with age?

We aim at identifying the characteristics of the neuronal ensembles engaged during recognition memory and the cellular mechanisms underlying their formation. For this purpose, we investigate how neurons within the MTL and the PFC connect to form so-called ‘engrams’, whether and how engrams from these distant brain areas interact with each other to improve recognition memory and how this relationship progresses in the old age.   

A vast interindividual differences in the ability to remember

Why some have a better memory than others is not yet well understood. In some cases pathologies such as neurodegenerative diseases play a role. However, even in healthy individuals, the ability to recall a place, an individual or other features of a memory can vary from poor to exceptional. This difference might reflect the existence of yet not fully exploited resources that could be harvested to improve performance. Such a range of performance is also observed in aged populations for which memory deficits but also memory performance comparable to that of young subjects are reported, as is the case for ‘Superagers’. Interestingly such differences are also reported in a various range of species, including rodents. Previous studies have suggested that the degree of activity of neurons prior to the formation of a memory are critical in determining whether a neuron will be integrated into an engram (Josselyn et al. Science 2020). We hypothesize that the size of the engram and the relationship between the engrams formed in the MTL and the PFC, i.e. the communication between these engrams, might also play a key role to achieve optimal recognition memory performance.

The goals of our project

We are studying whether connectivity within and between the MTL and the PFC might constitute a resource for recognition memory. For this, we investigate:  which and how specific subsets of neurons of these areas are recruited into ‘engrams’ to support memory formation and enable memory retrieval, the cellular mechanism underlying the formation of these engrams and the relationship between MTL and PFC engrams. We do so by identifying key interindividual differences between poor and good performers on object recognition memory tasks using engram mapping (Beer and Vavra, Plos Biology, 2018) and in-vitro electrophysiological techniques. In addition, we investigate how these mechanisms evolves with age and implement behavioral and optogenetic manipulations to improve/rescue memory performance, i.e. cognitive training/optical priming of brain-wide axonal connections (Klavir & Prigge et al, Nature Neuroscience 2017).

How to identify neuronal engrams

To identify selectively neurons recruited during the formation and the recall of memory, we take advantage of high resolution engram mapping techniques. Detecting the product of immediate early genes tied to memory function allow us to identify engrams at the cellular level. The use of fluorescent proteins that have the ability to change color when cells are active (CaMpari) makes it possible to label neurons that are active during memory recall or formation and to subsequently identify their cellular properties by using in-vitro electrophysiology. The results of these projects aim at complementing project B02, that focuses on similar questions in humans using functional magnetic tomography, by providing a mapping of MTL and PFC cognitive resource areas with cellular resolution and by proposing cellular mechanisms contributing to the formation of engrams.

Cognitive training, transfer and priming of HIP-PFC projections

Since the flow of information within the HIP and between the HIP and the PFC plays a crucial role in recognition memory, we examine whether interventions such as cognitive training or targeted brain stimulation can affect the size of engrams and synaptic connections between and within engrams at these levels. For this purpose, we use cognitive training that requires for subjects to perform repeatedly the same task, for example an object recognition memory task, with the aim of improving performance in this task. Importantly, we also investigate if the improvement observed in this given task, and the related changes in engram features, is transferable to different domains (in the present case: to the spatial and temporal domains). We test the hypothesis that neuronal engrams for different cognitive domains partially overlap and that improving performance in one given domain might be transferable to others. We also test whether increasing the level of excitability of HIP neurons specifically projecting to PFC increases their likelihood to be integrated into functional engrams. We expect the effect of manipulations to be especially beneficial to older memory–impaired animals as opposed to young populations.

Sheena A Josselyn, Memory engrams: Recalling the past and imagining the future, SCIENCE, 3 Jan2020, Vol 367, Issue 6473

Beer Z, Vavra P, Atucha E, Rentzing K, Heinze HJ, Sauvage MM, The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3,PLoS Biol 16(8): e2006100

Klavir O, Prigge M, Sarel A, Paz R, Yizhar O., Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex, Nat Neurosci. 2017 Jun;20(6):836-844

Outlook

Through close collaborations with CRC1436 subprojects, we seek to understand the fundamental mechanisms underlying recognition memory and to identify and unlock available resources to improve/rescue performance. In the future, we aim at adapting to humans the cognitive manipulations that will be successful in delaying cognitive decline in aging and/or improve memory function in the present project and to develop non-invasive brain stimulation protocols achieving the same goals.

Publications